US 2008/0287445 A1Published application

Prokineticin 2 receptor antagonists

OwnerSteven J. Coats, Alexey B. Dyatkin +5inventors

InventorsSteven J. Coats, Alexey B. Dyatkin, Wei He, Joseph Lisko, Tamara Miskowski, Janet L. Ralbovsky, Mark Schulz

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Abstract

The present invention relates to certain novel compounds of Formula (I): and methods for the treatment of prokineticin 2 or prokinetin 2 receptor mediated disorders.

Claims42

Dependent claims

A method of treating or preventing a disease or condition in a mammal in which the disease or condition is affected by antagonism of prokineticin 2 receptors, which method comprises administering to a mammal in need thereof a therapeutically effective amount of compound of Formula (I):

wherein:
A1 is CF3, C1-4alkoxy, aryl, aryloxy, benzofused heterocyclyl, or heteroaryl;
wherein aryl, aryloxy, and heteroaryl are optionally substituted with pyrazol-1-yl or [1,2,3]thiadiazol-4-yl;
or aryl, aryloxy, the benzo portion of benzofused heterocyclyl, and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, halogen, nitro, halogenated C1-6alkyl, halogenated C1-6alkoxy, C1-6alkylthio, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkoxycarbonylamino, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, formyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, aminosulfonyl, C1-6alkylaminosulfonyl, and di(C1-6alkyl)aminosulfonyl;
provided that A1 is other than 3,5-di-t-butyl-phenyl;
L1 is —(CH2)r—, —CH2C2-4alkenyl-, or —CH2CH2X(CH2)s—, wherein L1 is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
and, r is an integer of 1 to 5;
such that r is greater than or equal to 4 when A1 is C1-4alkoxy;
s is an integer of 1 to 3;
X is O or S;
D is —P-A2;
wherein P is —(CH2)1-2— or —CH2CH═CH— when A2 is phenyl, benzofused heterocyclyl, heteroaryl, or C3-8cycloalkyl;
alternatively, P is —(CH2)3-6— when A2 is hydrogen, C1-4alkoxy, or C1-4alkoxycarbonyl;
and wherein P is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
A2 is hydrogen, C1-4alkoxy, C1-4alkoxycarbonyl, phenyl, benzofused heterocyclyl, heteroaryl, tetrahydro-pyranyl, piperidinyl, or C3-8cycloalkyl;
wherein phenyl, heteroaryl, the benzo portion of benzofused heterocyclyl, and C3-8cycloalkyl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, halogen, halogenated C1-6alkyl, halogenated C1-6alkoxy, aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, nitro, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkylcarbonylamino, and a non fused C3-6cycloalkyloxy;
such that no more than two substituents on A2 are aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, or a non fused C3-6cycloalkyloxy;
provided that A2 is other than 3,5-di-t-butyl-phenyl;
W is N or C(RW);
wherein RW is H or C1-2alkyl;
Q is selected from the group consisting of (a) to (g), wherein
(a) is —NH(CH2)2—Ar1 wherein Ar1 is pyridinyl optionally substituted one to three C1-4alkyl substituents or a substituent selected from the group consisting of C1-4alkoxy and amino;
provided that when Ar1 is unsubstituted pyridin-3-yl or unsubstituted pyridin-4-yl, and A2 is 4-methoxy-phenyl, A1 is other than unsubstituted phenyl or 3,4-dichloro-phenyl;
(b) is —NHCH(Rz)—Ar2 wherein Rz is H or C1-3alkyl;
Ar2 is pyridinyl, pyrimidinyl, pyrazinyl,
1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
and wherein Ar2 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, trifluoromethyl, hydroxyl-C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, C3-8 cycloalkylamino, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
or Ar2 is optionally substituted with one amino group and three substituents independently selected from the group consisting of C1-4alkyl and C1-4alkoxy;
wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, C1-4alkylthio, hydroxy, a 5 to 6 membered heteroaryl, or a 5 to 6 membered heterocyclyl;
wherein a nitrogen atom of the 5 to 6 membered heterocyclyl is optionally substituted with a C1-4alkyl substituent;
and wherein pyridin-2-yl and pyridin-3-yl are optionally further substituted with N-pyrrolidinyl, N-piperazinyl, N-piperidinyl, N-morpholinyl, N-thiomorpholinyl, —CH2—O—CH2PH, and phenyl;
wherein the phenyl substituent of pyridin-2-yl and pyridin-3-yl is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and halogen;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is pyridin-4-yl, 4-C1-6alkyl-phenyl, 3,4-dichloro-phenyl, or 4-methanesulfonyl-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2— or —(CH2)5—, and A1 is methoxy, A2 is other than 4-difluoromethoxy-phenyl or 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is benzotriazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)3—, and A1 is pyrrol-1-yl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2—, and A1 is 4-nitro-phenyl or ethoxy, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-fluoro-phenyl;
provided that when Q is —NHCH2(6-amino-pyridin-2-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-trifluoromethoxy-phenyl;
provided that when Q is —NHCH2(6-methyl-pyridin-2-yl), and A1 is 4-methoxy-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(imidazo[1,2-a]pyridinyl), and A1 is 4-fluoro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(pyridin-4-yl), and A1 is unsubstituted phenyl or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), and A1 is 4-methoxy-phenyl, —P-A2 is other than —(CH2)5-methoxy;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), L1 is —(CH2)2—, and A1 is pyrazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 4-methoxy-phenyl, A2 is other than 2-ethyl-phenyl, 4-ethyl-phenyl, 3-methoxy-phenyl, 3-cyano-phenyl, 3-nitro-phenyl, and 3-trifluoromethyl-4-nitro-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is quinolin-8-yl, benzotriazol-1-yl, 3,5-dimethyl-pyrazolyl, 2-fluoro-phenyl, 2-chloro-phenyl, 2-nitro-phenyl, 2-trifluoromethyl-phenyl, 2-difluoromethoxy-phenyl, 3-difluoromethoxy-phenyl, 2-trifluoromethoxy-phenyl, 2,4-difluoro-phenyl, 2,6-difluoro-phenyl, 2,6-dichloro-phenyl, 2-chloro-4-fluoro-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 4-trifluoromethoxy-phenyl, A2 is other than 4-difluoromethoxy-phenyl;
and, provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 3-nitro-4-methoxy-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
(c) is —CH2NHCH2—Ar3, wherein W is N or CH, and Ar3 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and that the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar3 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(d) is —(CH2)2—Ar4, wherein Ar4 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar4 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(e) is —CH═CH—Ar5;
wherein Ar5 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, .3, or 4-position;
wherein Ar5 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(f) is —O—CH(R1)—Ar6 when W is CH;
or, (f) is —S—CH(R1)—Ar6 and W is N or CH;
wherein R1 is hydrogen or C1-4alkyl, and Ar6 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar6 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O—CH(R1)—Ar6, A1 and A2 are 4-methoxy-phenyl, and R1 is hydrogen, Ar6 is other than unsubstituted pyridin-2-yl or 2-amino-pyridin-4-yl;
and
(g) is —X1—(CH(Rx))2—Ar7 when W is CH;
wherein X1 is O or S, Rx is H or C1-4alkyl, and Ar7 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar7 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O(CH2)2—Ar7 and A1 and A2 are 4-methoxy-phenyl, Ar7 is other than unsubstituted pyridin-2-yl or unsubstituted pyridin-3-yl;
wherein a nitrogen atom of Ar1, Ar2, Ar3, Ar4, Ar5, Ar6, and Ar7 is optionally substituted with oxo;
and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof.

72 more elements

wherein:
A1 is aryl, heteroaryl, or a benzofused heterocyclyl selected from the group consisting of benzo[1,3]dioxalyl and 2,3-dihydro-benzofuranyl;
wherein aryl and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, nitro, fluoro, chloro, iodo, halogenated C1-4alkyl, halogenated C1-4alkoxy, and C1-4alkylthio;
provided that A1 is other than 3,5-di-t-butyl-phenyl;
L1 is —(CH2)r—, wherein L1 is optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl and C2-4alkenyl and r is 1 or 2;
D is —P-A2;
wherein P is —(CH2)1-2— when A2 is phenyl, benzofused heterocyclyl, heteroaryl, or C3-8cycloalkyl;
alternatively, P is —(CH2)4—, when A2 is hydrogen, C1-4alkoxy, or C1-4alkoxycarbonyl;
A2 is hydrogen, C1-4alkoxy, C1-4alkoxycarbonyl, phenyl, benzofused heterocyclyl, heteroaryl other than pyridin-4-yl, or C3-8cycloalkyl;
wherein phenyl, heteroaryl and C3-8cycloalkyl are optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, fluoro, chloro, halogenated C1-6alkoxy, phenyl, N-isoindole-1,3-dione, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, nitro, hydroxy, and C1-6alkylcarbonylamino;
provided that no more than one substituent of A2 is phenyl or N-isoindole-1,3-dione;
and provided that A2 is other than 3,5-di-t-butyl-phenyl;
W is CH or N;
Q is selected from the group consisting of (a)-(g) wherein:
(a) is —NH(CH2)2—Ar1 wherein Ar1 is pyridinyl substituted with one to three C1-4alkyl substituents or a substituent selected from the group consisting of C1-4alkoxy and amino;
(b) is —NHCH2—Ar2 wherein Ar2 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
and wherein Ar2 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, trifluoromethyl, C1-4alkoxy, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with (C1-4alkyl)amino, di(C1-4alkyl)amino, C1-4alkoxy, C1-4alkylthio, hydroxy, a 5 to 6 membered heteroaryl, or a 5 to 6 membered heterocyclyl;
wherein a nitrogen atom of the 5 to 6 membered heterocyclyl is optionally substituted with a C1-4alkyl substituent;
and wherein pyridin-2-yl and pyridin-3-yl are optionally further substituted with N-pyrrolidinyl, N-piperazinyl, N-piperidinyl, N-morpholinyl, N-thiomorpholinyl, and phenyl;
wherein the phenyl substituent of pyridin-2-yl and pyridin-3-yl is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and halogen;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is pyridin-4-yl, 4- C1-4alkyl-phenyl or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is benzotriazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2—, and A1 is 4-nitro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-fluoro-phenyl;
provided that when Q is —NHCH2(6-amino-pyridin-2-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-trifluoromethoxy-phenyl;
provided that when Q is —NHCH2(6-methyl-pyridin-2-yl), and A1 is 4-methoxy-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(imidazo[1,2-a]pyridinyl), and A1 is 4-fluoro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(pyridin-4-yl), and A1 is unsubstituted phenyl or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), and A1 is 4-methoxy-phenyl, —P-A2 is other than —(CH2)5-methoxy;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), L1 is —(CH2)2—, and A1 is pyrazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 4-methoxy-phenyl, A2 is other than 2-ethyl-phenyl, 4-ethyl-phenyl, 3-methoxy-phenyl, and 3-nitro-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is quinolin-8-yl, benzotriazol-1-yl, 3,5-dimethyl-pyrazolyl, 2-fluoro-phenyl, 2-chloro-phenyl, 2-nitro-phenyl, 2-trifluoromethyl-phenyl, 2-difluoromethoxy-phenyl, 3-difluoromethoxy-phenyl, 2-trifluoromethoxy-phenyl, 2,4-difluoro-phenyl, 2,6-difluoro-phenyl, 2,6-dichloro-phenyl, 2-chloro-4-fluoro-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 4-trifluoromethoxy-phenyl, A2 is other than 4-difluoromethoxy-phenyl;
and, provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 3-nitro-4-methoxy-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
(c) is —CH2NHCH2—Ar3, wherein W is N or CH, and Ar3 is pyridinyl optionally substituted with amino;
(d) is —(CH2)2—Ar4, wherein Ar4 is pyridinyl, or pyrimidinyl;
wherein Ar4 is optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
(e) is —CH═CH-pyridinyl;
(f) is —O—CH(R1)—Ar6 when W is CH;
or, (f) is —S—CH(R1)—Ar6 and W is N or CH;
wherein R1 is hydrogen or C1-4alkyl, and Ar6 is pyridinyl or pyrimidinyl;
wherein Ar6 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O—CH(R1)—Ar6, A1 and A2 are 4-methoxy-phenyl, and R1 is hydrogen, Ar6 is other than unsubstituted pyridin-2-yl or 2-amino-pyridin-4-yl;
and
(g) is —X1—(CH(Rx))2—Ar7 and W is CH;
wherein X, is O, Rx is H, and Ar7 is pyridinyl or pyrimidinyl;
wherein Ar7 is optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
provided that when Q is —O(CH2)2—Ar7 and A1 and A2 are 4-methoxy-phenyl, Ar7 is other than unsubstituted pyridin-2-yl or unsubstituted pyridin-3-yl;
wherein a nitrogen atom of Ar1, Ar2, Ar3, Ar4, Ar6, and Ar7 is optionally substituted with oxo;
and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof.

49 more elements

selected from the group consisting of
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is
a compound of Formula (I) wherein A1 is 4-chloro-phenyl, L1 is CH2, D is —(CH2)5OCH3, W is N, and Q is
a compound of Formula (I) wherein A1 is 3,4-dichloro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(pyridin-2-yl)ethyl-amino;
a compound of Formula (I) wherein A1 is 3,4-dichloro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-chloro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 5-amino-pyridin-2-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-chloro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 6-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4-amino-pyrimidin-5-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-amino-pyridin-3-ylmethyl-aminomethyl;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-quinolin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-amino-pyridin-3-yl)-ethylamino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-N-pyrrolidinyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-N-piperazinyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-N-piperidinyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-methylamino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-n-propylamino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-n-butylamino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-N-morpholino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-N-thiomorpholino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-ethylamino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-N-morpholino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W. is N, and Q is 1,2,3,4-tetrahydro-[1,8]naphthyridin-7-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzofuran-2-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methylthio-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 6-(4-fluoro-phenyl)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-dimethylamino-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-methoxy-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-hydroxy-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-amino-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-cyclohexylamino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is N-oxo-2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-hydroxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-n propylamino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxycarbonyl-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methylcarbonylamino-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-trifluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is pyridin-2-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is pyridin-4-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 3-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-cyano-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-trifluoromethoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-ethoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-nitro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH(allyl), D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-trifluoromethyl-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-methoxy-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-dimethylamino-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-aminocarbonyl-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is N-oxo-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-hydroxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 3-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxycarbonyl-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-5-phenyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L, is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-4-methoxy-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 6-methyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4-methyl-pyridin-2-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-ethyl-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 6-trifluoromethyl-pyridin-2-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 3-methyl-pyridin-2-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-methylthio-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(3-methyl-butylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(tetrahydro-furan-2-ylmethyl)-amino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(furan-2-ylmethyl-amino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(N-ethyl-pyrrolidin-2-ylmethyl-amino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is phenyl, L1 is CH2CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-methoxy-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is phenoxy, L1 is CH2CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-methoxy-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2,3-dihydro-benzo[1,4]dioxin-2-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-methoxy-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-nitro-phenyl, L1 is CH2CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(2-methoxy-ethylamino)-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methylthio-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is pyridin-4-ylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is benzofuran-2-ylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 5-methoxy-n-pentyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is n-hexyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-cyano-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-nitro-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-difluoromethoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-difluoromethoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-difluoromethoxy-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2-ethyl-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2-trifluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2-cyano-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-iodo-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-pyrazol-1-yl-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-trifluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-methoxycarbonyl-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2-(4-methoxy-phenyl)-ethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 6-methoxy-pyridin-3-ylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-trifluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-trifluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methylthio-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is pyridin-4-ylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is benzofuran-2-ylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is n-hexyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 6-methoxy-pyridin-3-ylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2-trifluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-ethoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-nitro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH(allyl), D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-trifluoromethyl-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 3-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 3-fluoro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is pyridin-4-ylmethyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxycarbonyl-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 6-amino-pyridin-2-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-fluoro-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-chloro-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is N-oxo-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is indol-3-yl, L1 is CH2CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2,3-dihydro-benzo[1,4]dioxin-2-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is pyridin-3-ylmethoxy;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 6-trifluoromethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2,3-dihydro-benzofuran-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 3-nitro-4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2,3-dihydro-benzofuran-5-ylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is benzofuran-5-ylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is indol-5-ylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2,3-dihydro-benzofuran-5-ylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is benzofuran-5-ylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is indol-5-ylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methanesulfonyl-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methanesulfonyl-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzofuran-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzofuran-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-t-butoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-nitro-4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-nitro-4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is indol-4-ylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is indol-4-ylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is benzothiophen-5-ylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenoxy, L1 is CH2CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is benzothiophen-5-ylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzothiophen-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzothiophen-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 6-n-propylamino-pyridin-2-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 6-amino-pyridin-2-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-cyclohexylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-cyclohexylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3,4-dichloro-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-(isoindol-1,3-dione-2-yl)-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-methoxycarbonyl-n-propyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-pyridin-2-yl-ethylamino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is indol-4-ylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 6-amino-pyridin-2-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2,3-dihydro-benzofuran-5-ylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-pyrazol-1-yl-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-iodo-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methyl-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-trifluoromethyl-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-difluoromethoxy-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-cyano-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxycarbonyl-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is phenoxy, L1 is CH2CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-fluoro-phenoxy, L1 is CH2CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-[1,2,3]thiadiazol-4-yl-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-pyridin-3-yl-ethyl;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is indol-6-ylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is indol-7-ylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is indol-7-ylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methylthio-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzothiophen-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzofuran-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2,3-dihydro-benzofuran-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methylthio-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzofuran-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2,3-dihydro-benzofuran-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2-cyano-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-hydroxy-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methylcarbonyloxy-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenyl, W is CH, and Q is 2-pyridin-4-yl-ethyl;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenyl, W is CH, and Q is cis-2-pyridin-4-yl-vinyl;
a compound of Formula (I) wherein A1 is 2,3-dihydro-benzofuran-5-yl, L1 is CH2, D is 2,3-dihydro-benzofuran-5-ylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzofuran-5-yl, L1 is CH2, D is 2,3-dihydro-benzofuran-5-ylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-pyridin-2-yl-ethyl;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is imidazo[1,2-a]pyridin-8-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-(2-aminocarbonyl-pyridin-3-yl)-ethyl;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-amino-pyridin-3-ylmethoxy;
a compound of Formula (I) wherein A1 is 4-hydroxymethyl-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 1-methyl-1H-benzotriazol-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2-methoxy-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-aminocarbonyl-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2,6-difluoro-4-methoxy-phenyl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzo[1,2,3]thiadiazol-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is methoxy, L1 is (CH2)5, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is methoxy, L1 is (CH2)5, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-(2-amino-pyridin-3-yl)-ethyl;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2,4-dimethoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4-methyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethoxy;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-fluoro-4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 3-fluoro-4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2-fluoro-4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2-fluoro-4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzo(1,3)dioxal-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzo(1,3)dioxal-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2,3-dihydro-benzo[1,4]dioxin-6-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 2,3-dihydro-benzo[1,4]dioxin-6-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is pyridin-3-ylmethylthio;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 2-methyl-2,3-dihydro-benzofuran-5-ylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(N-piperidinyl)-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-(4-amino-pyridin-3-yl)-ethyl;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-(pyridin-4-yl)-ethylamino;
a compound of Formula (I) wherein A1 is 1-methyl-1H-benzotriazol-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethylpyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzo[1,2,3]thiadiazol-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 3-fluoro-4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzo(1,3)dioxal-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is benzo(1,3)dioxal-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 1-methyl-1H-benzotriazol-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 1-methyl-1H-benzotriazol-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-(6-amino-pyridin-2-yl)ethyl;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 5-methoxy-n-pentyl, W is N, and Q is 2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 1-(2-amino-pyridin-4-yl)-ethoxy;
a compound of Formula (I) wherein A1 is 2,3-dihydro-benzofuran-5-yl, L1 is CH2, D is 2,3-dihydro-benzofuran-5-ylmethyl, W is N, and Q is N-oxo-2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is indol-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is indol-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is indol-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 4,6-dimethyl-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is indol-5-yl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-chloro-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is N, and Q is 2-amino-pyridin-3-ylmethyl-amino;
a compound of Formula (I) wherein A1 is 4-methoxy-phenyl, L1 is CH2, D is 4-methoxy-phenylmethyl, W is CH, and Q is 2-amino-pyrimidin-4-ylmethoxy;
a compound of Formula (I) wherein A1 is 2,3-dihydro-benzofuran-5-yl, L1 is CH2, D is 4-difluoromethoxy-phenylmethyl, W is N, and Q is N-oxo-2-amino-4,6-dimethyl-pyridin-3-ylmethyl-amino;
and combinations thereof.

235 more elements

A method of treating or preventing a disease or condition in a mammal in which the disease or condition is affected by antagonism of prokineticin 2 receptors, which method comprises administering to a mammal in need thereof a pharmaceutical composition comprising a therapeutically effective amount of compound of Formula (I):

wherein:
A1 is CF3, C1-4alkoxy, aryl, aryloxy, benzofused heterocyclyl, or heteroaryl;
wherein aryl, aryloxy, and heteroaryl are optionally substituted with pyrazol-1-yl or [1,2,3]thiadiazol-4-yl;
or aryl, aryloxy, the benzo portion of benzofused heterocyclyl, and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, halogen, nitro, halogenated C1-6alkyl, halogenated C1-6alkoxy, C1-6alkylthio, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkoxycarbonylamino, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, formyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, aminosulfonyl, C1-6alkylaminosulfonyl, and di(C1-6alkyl)aminosulfonyl;
provided that A1 is other than 3,5-di-t-butyl-phenyl;
L1 is —(CH2)r—, —CH2C2-4alkenyl-, or —CH2CH2X(CH2)s—, wherein L1 is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
and, r is an integer of 1 to 5;
such that r is greater than or equal to 4 when A1 is C1-4alkoxy;
s is an integer of 1 to 3;
X is O or S;
D is —P-A2;
wherein P is —(CH2)1-2— or —CH2CH═CH— when A2 is phenyl, benzofused heterocyclyl, heteroaryl, or C3-8cycloalkyl;
alternatively, P is —(CH2)3-6— when A2 is hydrogen, C1-4alkoxy, or C1-4alkoxycarbonyl;
and wherein P is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
A2 is hydrogen, C1-4alkoxy, C1-4alkoxycarbonyl, phenyl, benzofused heterocyclyl, heteroaryl, tetrahydro-pyranyl, piperidinyl, or C3-8cycloalkyl;
wherein phenyl, heteroaryl, the benzo portion of benzofused heterocyclyl, and C3-8cycloalkyl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, halogen, halogenated C1-6alkyl, halogenated C1-6alkoxy, aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, nitro, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkylcarbonylamino, and a non fused C3-6cycloalkyloxy;
such that no more than two substituents on A2 are aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, or a non fused C3-6cycloalkyloxy;
provided that A2 is other than 3,5-di-t-butyl-phenyl;
W is N or C(RW);
wherein RW is H or C1-2alkyl;
Q is selected from the group consisting of (a) to (g), wherein
(a) is —NH(CH2)2—Ar1 wherein Ar1 is pyridinyl optionally substituted one to three C1-4alkyl substituents or a substituent selected from the group consisting of C1-4alkoxy and amino;
provided that when Ar1 is unsubstituted pyridin-3-yl or unsubstituted pyridin-4-yl, and A2 is 4-methoxy-phenyl, A1 is other than unsubstituted phenyl or 3,4-dichloro-phenyl;
(b) is —NHCH(Rz)—Ar2 wherein Rz is H or C1-3alkyl;
Ar2 is pyridinyl, pyrimidinyl, pyrazinyl,
1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
and wherein Ar2 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, trifluoromethyl, hydroxyl-C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, C3-8 cycloalkylamino, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
or Ar2 is optionally substituted with one amino group and three substituents independently selected from the group consisting of C1-4alkyl and C1-4alkoxy;
wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, C1-4alkylthio, hydroxy, a 5 to 6 membered heteroaryl, or a 5 to 6 membered heterocyclyl;
wherein a nitrogen atom of the 5 to 6 membered heterocyclyl is optionally substituted with a C1-4alkyl substituent;
and wherein pyridin-2-yl and pyridin-3-yl are optionally further substituted with N-pyrrolidinyl, N-piperazinyl, N-piperidinyl, N-morpholinyl, N-thiomorpholinyl, —CH2—O—CH2—PH, and phenyl;
wherein the phenyl substituent of pyridin-2-yl and pyridin-3-yl is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and halogen;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is pyridin-4-yl, 4-C1-6alkyl-phenyl, 3,4-dichloro-phenyl, or 4-methanesulfonyl-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2— or —(CH2)5—, and A1 is methoxy, A2 is other than 4-difluoromethoxy-phenyl or 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is benzotriazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)3—, and A1 is pyrrol-1-yl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2—, and A1 is 4-nitro-phenyl or ethoxy, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-fluoro-phenyl;
provided that when Q is —NHCH2(6-amino-pyridin-2-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-trifluoromethoxy-phenyl;
provided that when Q is —NHCH2(6-methyl-pyridin-2-yl), and A1 is 4-methoxy-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(imidazo[1,2-a]pyridinyl), and A1 is 4-fluoro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(pyridin-4-yl), and A1 is unsubstituted phenyl or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), and A1 is 4-methoxy-phenyl, —P-A2 is other than —(CH2)5-methoxy;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), L1 is —(CH2)2—, and A1 is pyrazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 4-methoxy-phenyl, A2 is other than 2-ethyl-phenyl, 4-ethyl-phenyl, 3-methoxy-phenyl, 3-cyano-phenyl, 3-nitro-phenyl, and 3-trifluoromethyl-4-nitro-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is quinolin-8-yl, benzotriazol-1-yl, 3,5-dimethyl-pyrazolyl, 2-fluoro-phenyl, 2-chloro-phenyl, 2-nitro-phenyl, 2-trifluoromethyl-phenyl, 2-difluoromethoxy-phenyl, 3-difluoromethoxy-phenyl, 2-trifluoromethoxy-phenyl, 2,4-difluoro-phenyl, 2,6-difluoro-phenyl, 2,6-dichloro-phenyl, 2-chloro-4-fluoro-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 4-trifluoromethoxy-phenyl, A2 is other than 4-difluoromethoxy-phenyl;
and, provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 3-nitro-4-methoxy-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
(c) is —CH2NHCH2—Ar3, wherein W is N or CH, and Ar3 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and that the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar3 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(d) is —(CH2)2—Ar4, wherein Ar4 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar4 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(e) is —CH═CH—Ar5;
wherein Ar5 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar5 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(f) is —O—CH(R1)—Ar6 when W is CH;
or, (f) is —S—CH(R1)—Ar6 and W is N or CH;
wherein R1 is hydrogen or C1-4alkyl, and Ar6 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar6 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O—CH(R1)—Ar6, A1 and A2 are 4-methoxy-phenyl, and R1 is hydrogen, Ar6 is other than unsubstituted pyridin-2-yl or 2-amino-pyridin-4-yl;
and
(g) is —X1—(CH(Rx))2—Ar7 when W is CH;
wherein X1 is O or S, Rx is H or C1-4alkyl, and Ar7 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar7 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O(CH2)2—Ar7 and A1 and A2 are 4-methoxy-phenyl, Ar7 is other than unsubstituted pyridin-2-yl or unsubstituted pyridin-3-yl;
wherein a nitrogen atom of Ar1, Ar2, Ar3, Ar4, Ar5, Ar6, and Ar7 is optionally substituted with oxo;
and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof,
said compound of Formula (I) admixed with a pharmaceutically acceptable carrier, excipient or diluent.

73 more elements

A method of reducing and/or treating inflammation in the intestine of a mammal in need thereof, comprising administering to the mammal a compound of compound of Formula (I):

wherein:
A1 is CF3, C1-4alkoxy, aryl, aryloxy, benzofused heterocyclyl, or heteroaryl;
wherein aryl, aryloxy, and heteroaryl are optionally substituted with pyrazol-1-yl or [1,2,3]thiadiazol-4-yl;
or aryl, aryloxy, the benzo portion of benzofused heterocyclyl, and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, halogen, nitro, halogenated C1-6alkyl, halogenated C1-6alkoxy, C1-6alkylthio, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkoxycarbonylamino, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, formyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, aminosulfonyl, C1-6alkylaminosulfonyl, and di(C1-6alkyl)aminosulfonyl;
provided that A1 is other than 3,5-di-t-butyl-phenyl;
L1 is —(CH2)r—, —CH2C2-4alkenyl-, or —CH2CH2X(CH2)s—, wherein L1 is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
and, r is an integer of 1 to 5;
such that r is greater than or equal to 4 when A1 is C1-4alkoxy;
s is an integer of 1 to 3;
X is O or S;
D is —P-A2;
wherein P is —(CH2)1-2— or —CH2CH═CH— when A2 is phenyl, benzofused heterocyclyl, heteroaryl, or C3-8cycloalkyl;
alternatively, P is —(CH2)3-6— when A2 is hydrogen, C1-4alkoxy, or C1-4alkoxycarbonyl;
and wherein P is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
A2 is hydrogen, C1-4alkoxy, C1-4alkoxycarbonyl, phenyl, benzofused heterocyclyl, heteroaryl, tetrahydro-pyranyl, piperidinyl, or C3-8cycloalkyl;
wherein phenyl, heteroaryl, the benzo portion of benzofused heterocyclyl, and C3-8cycloalkyl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, halogen, halogenated C1-6alkyl, halogenated C1-6alkoxy, aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, nitro, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkylcarbonylamino, and a non fused C3-6cycloalkyloxy;
such that no more than two substituents on A2 are aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, or a non fused C3-6cycloalkyloxy;
provided that A2 is other than 3,5-di-t-butyl-phenyl;
W is N or C(RW);
wherein RW is H or C1-2alkyl;
Q is selected from the group consisting of (a) to (g), wherein
(a) is —NH(CH2)2—Ar1 wherein Ar1 is pyridinyl optionally substituted one to three C1-4alkyl substituents or a substituent selected from the group consisting of C1-4alkoxy and amino;
provided that when Ar1 is unsubstituted pyridin-3-yl or unsubstituted pyridin-4-yl, and A2 is 4-methoxy-phenyl, A1 is other than unsubstituted phenyl or 3,4-dichloro-phenyl;
(b) is —NHCH(Rz)—Ar2 wherein Rz is H or C1-3alkyl;
Ar2 is pyridinyl, pyrimidinyl, pyrazinyl,
1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
and wherein Ar2 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, trifluoromethyl, hydroxyl-C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, C3-8 cycloalkylamino, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
or Ar2 is optionally substituted with one amino group and three substituents independently selected from the group consisting of C1-4alkyl and C1-4alkoxy;
wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, C1-4alkylthio, hydroxy, a 5 to 6 membered heteroaryl, or a 5 to 6 membered heterocyclyl;
wherein a nitrogen atom of the 5 to 6 membered heterocyclyl is optionally substituted with a C1-4alkyl substituent;
and wherein pyridin-2-yl and pyridin-3-yl are optionally further substituted with N-pyrrolidinyl, N-piperazinyl, N-piperidinyl, N-morpholinyl, N-thiomorpholinyl, —CH2—O—CH2—PH, and phenyl;
wherein the phenyl substituent of pyridin-2-yl and pyridin-3-yl is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and halogen;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is pyridin-4-yl, 4-C1-6alkyl-phenyl, 3,4-dichloro-phenyl, or 4-methanesulfonyl-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2— or —(CH2)5—, and A1 is methoxy, A2 is other than 4-difluoromethoxy-phenyl or 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is benzotriazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)3—, and A1 is pyrrol-1-yl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2—, and A1 is 4-nitro-phenyl or ethoxy, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-fluoro-phenyl;
provided that when Q is —NHCH2(6-amino-pyridin-2-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-trifluoromethoxy-phenyl;
provided that when Q is —NHCH2(6-methyl-pyridin-2-yl), and A1 is 4-methoxy-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(imidazo[1,2-a]pyridinyl), and A1 is 4-fluoro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(pyridin-4-yl), and A1 is unsubstituted phenyl or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), and A1 is 4-methoxy-phenyl, —P-A2 is other than —(CH2)5-methoxy;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), L1 is —(CH2)2—, and A1 is pyrazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 4-methoxy-phenyl, A2 is other than 2-ethyl-phenyl, 4-ethyl-phenyl, 3-methoxy-phenyl, 3-cyano-phenyl, 3-nitro-phenyl, and 3-trifluoromethyl-4-nitro-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is quinolin-8-yl, benzotriazol-1-yl, 3,5-dimethyl-pyrazolyl, 2-fluoro-phenyl, 2-chloro-phenyl, 2-nitro-phenyl, 2-trifluoromethyl-phenyl, 2-difluoromethoxy-phenyl, 3-difluoromethoxy-phenyl, 2-trifluoromethoxy-phenyl, 2,4-difluoro-phenyl, 2,6-difluoro-phenyl, 2,6-dichloro-phenyl, 2-chloro-4-fluoro-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 4-trifluoromethoxy-phenyl, A2 is other than 4-difluoromethoxy-phenyl;
and, provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 3-nitro-4-methoxy-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
(c) is —CH2NHCH2-Ar3, wherein W is N or CH, and Ar3 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and that the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar3 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(d) is —(CH2)z—Ar4, wherein Ar4 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar4 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(e) is —CH═CH—Ar5;
wherein Ar5 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar5 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(f) is —CH(R1)—Ar6 when W is CH ;
or, (f) is —S—CH(R1)—Ar6 and W is N or CH;
wherein R1 is hydrogen or C1-4alkyl, and Ar6 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar6 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O—CH(R1)—Ar6, A1 and A2 are 4-methoxy-phenyl, and R1 is hydrogen, Ar6 is other than unsubstituted pyridin-2-yl or 2-amino-pyridin-4-yl;
and
(g) is —X1—(CH(Rx))2—Ar7 when W is CH;
wherein X1 is O or S, Rx is H or C1-4alkyl, and Ar7 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar7 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O(CH2)2—Ar7 and A1 and A2 are 4-methoxy-phenyl, Ar7 is other than unsubstituted pyridin-2-yl or unsubstituted pyridin-3-yl;
wherein a nitrogen atom of Ar1, Ar2, Ar3, Ar4, Ar5, Ar6, and Ar7 is optionally substituted with oxo;
and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof,
wherein the inflammation in the intestine is reduced.

73 more elements

A method of inhibiting fluid secretion in intestinal lumen, comprising administering a compound of Formula (I):

wherein:
A1 is CF3, C1-4alkoxy, aryl, aryloxy, benzofused heterocyclyl, or heteroaryl;
wherein aryl, aryloxy, and heteroaryl are optionally substituted with pyrazol-1-yl or [1,2,3]thiadiazol-4-yl;
or aryl, aryloxy, the benzo portion of benzofused heterocyclyl, and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, halogen, nitro, halogenated C1-6alkyl, halogenated C1-6alkoxy, C1-6alkylthio, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkoxycarbonylamino, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, formyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, aminosulfonyl, C1-6alkylaminosulfonyl, and di(C1-6alkyl)aminosulfonyl;
provided that A1 is other than 3,5-di-t-butyl-phenyl;
L1 is —(CH2)r—, —CH2C2-4alkenyl-, or —CH2CH2X(CH2)s—, wherein L1 is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
and, r is an integer of 1 to 5;
such that r is greater than or equal to 4 when A1 is C1-4alkoxy;
s is an integer of 1 to 3;
X is O or S;
D is —P-A2;
wherein P is —(CH2)1-2— or —CH2CH═CH— when A2 is phenyl, benzofused heterocyclyl, heteroaryl, or C3-8cycloalkyl;
alternatively, P is —(CH2)3— when A2 is hydrogen, C1-4alkoxy, or C1-4alkoxycarbonyl;
and wherein P is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
A2 is hydrogen, C1-4alkoxy, C1-4alkoxycarbonyl, phenyl, benzofused heterocyclyl, heteroaryl, tetrahydro-pyranyl, piperidinyl, or C3-8cycloalkyl;
wherein phenyl, heteroaryl, the benzo portion of benzofused heterocyclyl, and C3-8cycloalkyl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, halogen, halogenated C1-6alkyl, halogenated C1-6alkoxy, aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, nitro, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkylcarbonylamino, and a non fused C3-6cycloalkyloxy;
such that no more than two substituents on A2 are aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, or a non fused C3-6cycloalkyloxy;
provided that A2 is other than 3,5-di-t-butyl-phenyl;
W is N or C(RW);
wherein RW is H or C1-2alkyl;
Q is selected from the group consisting of (a) to (g), wherein
(a) is —NH(CH2)2—Ar1 wherein Ar1 is pyridinyl optionally substituted one to three C1-4alkyl substituents or a substituent selected from the group consisting of C1-4alkoxy and amino;
provided that when Ar1 is unsubstituted pyridin-3-yl or unsubstituted pyridin-4-yl, and A2 is 4-methoxy-phenyl, A1 is other than unsubstituted phenyl or 3,4-dichloro-phenyl;
(b) is —NHCH(Rz)—Ar2 wherein Rz is H or C1-3alkyl;
Ar2 is pyridinyl, pyrimidinyl, pyrazinyl,
1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
and wherein Ar2 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, trifluoromethyl, hydroxyl-C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, C3-8 cycloalkylamino, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
or Ar2 is optionally substituted with one amino group and three substituents independently selected from the group consisting of C1-4alkyl and C1-4alkoxy;
wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, C1-4alkylthio, hydroxy, a 5 to 6 membered heteroaryl, or a 5 to 6 membered heterocyclyl;
wherein a nitrogen atom of the 5 to 6 membered heterocyclyl is optionally substituted with a C1-4alkyl substituent;
and wherein pyridin-2-yl and pyridin-3-yl are optionally further substituted with N-pyrrolidinyl, N-piperazinyl, N-piperidinyl, N-morpholinyl, N-thiomorpholinyl, —CH2—O—CH2—PH, and phenyl;
wherein the phenyl substituent of pyridin-2-yl and pyridin-3-yl is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and halogen;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is pyridin-4-yl, 4-C1-6alkyl-phenyl, 3,4-dichloro-phenyl, or 4-methanesulfonyl-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2— or —(CH2)5—, and A1 is methoxy, A2 is other than 4-difluoromethoxy-phenyl or 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is benzotriazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)3—, and A1 is pyrrol-1-yl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2—, and A1 is 4-nitro-phenyl or ethoxy, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-fluoro-phenyl;
provided that when Q is —NHCH2(6-amino-pyridin-2-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-trifluoromethoxy-phenyl;
provided that when Q is —NHCH2(6-methyl-pyridin-2-yl), and A1 is 4-methoxy-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(imidazo[1,2-a]pyridinyl), and A1 is 4-fluoro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(pyridin-4-yl), and A1 is unsubstituted phenyl or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), and A1 is 4-methoxy-phenyl, —P-A2 is other than —(CH2)5-methoxy;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), L1 is —(CH2)2—, and A1 is pyrazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 4-methoxy-phenyl, A2 is other than 2-ethyl-phenyl, 4-ethyl-phenyl, 3-methoxy-phenyl, 3-cyano-phenyl, 3-nitro-phenyl, and 3-trifluoromethyl-4-nitro-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is quinolin-8-yl, benzotriazol-1-yl, 3,5-dimethyl-pyrazolyl, 2-fluoro-phenyl, 2-chloro-phenyl, 2-nitro-phenyl, 2-trifluoromethyl-phenyl, 2-difluoromethoxy-phenyl, 3-difluoromethoxy-phenyl, 2-trifluoromethoxy-phenyl, 2,4-difluoro-phenyl, 2,6-difluoro-phenyl, 2,6-dichloro-phenyl, 2-chloro-4-fluoro-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 4-trifluoromethoxy-phenyl, A2 is other than 4-difluoromethoxy-phenyl;
and, provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 3-nitro-4-methoxy-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
(c) is —CH2NHCH2—Ar3, wherein W is N or CH, and Ar3 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and that the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar3 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(d) is —(CH2)2—Ar4, wherein Ar4 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar4 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(e) is —CH═CH—Ar5;
wherein Ar5 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar5 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(f) is —O—CH(R1)—Ar6 when W is CH ;
or, (f) is —S—CH(R1)—Ar6 and W is N or CH;
wherein R1 is hydrogen or C1-4alkyl, and Ar6 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar6 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O—CH(R1)—Ar6, A1 and A2 are 4-methoxy-phenyl, and R1 is hydrogen, Ar6 is other than unsubstituted pyridin-2-yl or 2-amino-pyridin-4-yl;
and
(g) is —X1—(CH(Rx))2—Ar7 when W is CH;
wherein X1 is O or S, Rx is H or C1-4alkyl, and Ar7 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar7 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O(CH2)2—Ar7 and A1 and A2 are 4-methoxy-phenyl, Ar7 is other than unsubstituted pyridin-2-yl or unsubstituted pyridin-3-yl;
wherein a nitrogen atom of Ar1, Ar2, Ar3, Ar4, Ar5, Ar6, and Ar7 is optionally substituted with oxo;
and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof.

72 more elements

A method of inhibiting propulsion in intestinal, comprising administering a compound of compound of Formula (I):

wherein:
A1 is CF3, C1-4alkoxy, aryl, aryloxy, benzofused heterocyclyl, or heteroaryl;
wherein aryl, aryloxy, and heteroaryl are optionally substituted with pyrazol-1-yl or [1,2,3]thiadiazol-4-yl;
or aryl, aryloxy, the benzo portion of benzofused heterocyclyl, and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, halogen, nitro, halogenated C1-6alkyl, halogenated C1-6alkoxy, C1-6alkylthio, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkoxycarbonylamino, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, formyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, aminosulfonyl, C1-6alkylaminosulfonyl, and di(C1-6alkyl)aminosulfonyl;
provided that A1 is other than 3,5-di-t-butyl-phenyl;
L1 is —(CH2)r—, —CH2C2-4alkenyl-, or —CH2CH2X(CH2)s—, wherein L1 is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
and, r is an integer of 1 to 5;
such that r is greater than or equal to 4 when A1 is C1-4alkoxy;
s is an integer of 1 to 3;
X is O or S;
D is —P-A2;
wherein P is —(CH2)1-2— or —CH2CH═CH— when A2 is phenyl, benzofused heterocyclyl, heteroaryl, or C3-8cycloalkyl;
alternatively, P is —(CH2)3-6— when A2 is hydrogen, C1-4alkoxy, or C1-4alkoxycarbonyl;
and wherein P is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
A2 is hydrogen, C1-4alkoxy, C1-4alkoxycarbonyl, phenyl, benzofused heterocyclyl, heteroaryl, tetrahydro-pyranyl, piperidinyl, or C3-8cycloalkyl;
wherein phenyl, heteroaryl, the benzo portion of benzofused heterocyclyl, and C3-8cycloalkyl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, halogen, halogenated C1-6alkyl, halogenated C1-6alkoxy, aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, nitro, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkylcarbonylamino, and a non fused C3-6cycloalkyloxy;
such that no more than two substituents on A2 are aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, or a non fused C3-6cycloalkyloxy;
provided that A2 is other than 3,5-di-t-butyl-phenyl;
W is N or C(RW);
wherein RW is H or C1-2alkyl;
Q is selected from the group consisting of (a) to (g), wherein
(a) is —NH(CH2)2—Ar1 wherein Ar1 is pyridinyl optionally substituted one to three C1-4alkyl substituents or a substituent selected from the group consisting of C1-4alkoxy and amino;
provided that when Ar1 is unsubstituted pyridin-3-yl or unsubstituted pyridin-4-yl, and A2 is 4-methoxy-phenyl, A1 is other than unsubstituted phenyl or 3,4-dichloro-phenyl;
(b) is —NHCH(Rz)—Ar2 wherein Rz is H or C1-3alkyl;
Ar2 is pyridinyl, pyrimidinyl, pyrazinyl,
1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
and wherein Ar2 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, trifluoromethyl, hydroxyl-C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, C3-8 cycloalkylamino, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
or Ar2 is optionally substituted with one amino group and three substituents independently selected from the group consisting of C1-4alkyl and C1-4alkoxy;
wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, C1-4alkylthio, hydroxy, a 5 to 6 membered heteroaryl, or a 5 to 6 membered heterocyclyl;
wherein a nitrogen atom of the 5 to 6 membered heterocyclyl is optionally substituted with a C1-4alkyl substituent;
and wherein pyridin-2-yl and pyridin-3-yl are optionally further substituted with N-pyrrolidinyl, N-piperazinyl, N-piperidinyl, N-morpholinyl, N-thiomorpholinyl, —CH2—O—CH2—PH, and phenyl;
wherein the phenyl substituent of pyridin-2-yl and pyridin-3-yl is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and halogen;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is pyridin-4-yl, 4-C1-6alkyl-phenyl, 3,4-dichloro-phenyl, or 4-methanesulfonyl-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2— or —(CH2)5—, and A1 is methoxy, A2 is other than 4-difluoromethoxy-phenyl or 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is benzotriazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)3—, and A1 is pyrrol-1-yl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2—, and A1 is 4-nitro-phenyl or ethoxy, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-fluoro-phenyl;
provided that when Q is —NHCH2(6-amino-pyridin-2-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-trifluoromethoxy-phenyl;
provided that when Q is —NHCH2(6-methyl-pyridin-2-yl), and A1 is 4-methoxy-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(imidazo[1,2-a]pyridinyl), and A1 is 4-fluoro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(pyridin-4-yl), and A1 is unsubstituted phenyl or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), and A1 is 4-methoxy-phenyl, —P-A2 is other than —(CH2)5-methoxy;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), L1 is —(CH2)2—, and A1 is pyrazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 4-methoxy-phenyl, A2 is other than 2-ethyl-phenyl, 4-ethyl-phenyl, 3-methoxy-phenyl, 3-cyano-phenyl, 3-nitro-phenyl, and 3-trifluoromethyl-4-nitro-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is quinolin-8-yl, benzotriazol-1-yl, 3,5-dimethyl-pyrazolyl, 2-fluoro-phenyl, 2-chloro-phenyl, 2-nitro-phenyl, 2-trifluoromethyl-phenyl, 2-difluoromethoxy-phenyl, 3-difluoromethoxy-phenyl, 2-trifluoromethoxy-phenyl, 2,4-difluoro-phenyl, 2,6-difluoro-phenyl, 2,6-dichloro-phenyl, 2-chloro-4-fluoro-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 4-trifluoromethoxy-phenyl, A2 is other than 4-difluoromethoxy-phenyl;
and, provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 3-nitro-4-methoxy-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
(c) is —CH2NHCH2Ar3, wherein W is N or CH, and Ar3 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and that the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar3 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(d) is —(CH2)z—Ar4, wherein Ar4 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar4 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(e) is —CH═CH—Ar5;
wherein Ar5 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar5 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(f) is —O—CH(R1)—Ar6 when W is CH ;
or, (f) is —S—CH(R1)—Ar6 and W is N or CH;
wherein R1 is hydrogen or C1-4alkyl, and Ar6 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar6 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O—CH(R1)—Ar6, A1 and A2 are 4-methoxy-phenyl, and R1 is hydrogen, Ar6 is other than unsubstituted pyridin-2-yl or 2-amino-pyridin-4-yl;
and
(g) is —X1—(CH(Rx))2—Ar7 when W is CH;
wherein X1 is O or S, Rx is H or C1-4alkyl, and Ar7 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar7 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is -(CH2)2—Ar7 and A1 and A2 are 4-methoxy-phenyl, Ar7 is other than unsubstituted pyridin-2-yl or unsubstituted pyridin-3-yl;
wherein a nitrogen atom of Ar1, Ar2, Ar3, Ar4, Ar5, Ar6, and Ar7 is optionally substituted with oxo;
and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof.

72 more elements

A method of treating or preventing a disease or condition in a mammal in which the disease or condition is affected by antagonism of prokineticin 2 receptors, which method comprises administering to a mammal in need thereof a veterinary composition comprising a therapeutically effective amount of compound of Formula (I):

wherein:
A1 is CF3, C1-4alkoxy, aryl, aryloxy, benzofused heterocyclyl, or heteroaryl;
wherein aryl, aryloxy, and heteroaryl are optionally substituted with pyrazol-1-yl or [1,2,3]thiadiazol-4-yl;
or aryl, aryloxy, the benzo portion of benzofused heterocyclyl, and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, halogen, nitro, halogenated C1-6alkyl, halogenated C1-6alkoxy, C1-6alkylthio, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkoxycarbonylamino, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, formyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, aminosulfonyl, C1-6alkylaminosulfonyl, and di(C1-6alkyl)aminosulfonyl;
provided that A1 is other than 3,5-di-t-butyl-phenyl;
L1 is —(CH2)r—, —CH2C2-4alkenyl-, or —CH2CH2X(CH2)s—, wherein L1 is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
and, r is an integer of 1 to 5;
such that r is greater than or equal to 4 when A1 is C1-4alkoxy;
s is an integer of 1 to 3;
X is O or S;
D is —P-A2;
wherein P is —(CH2)1-2— or —CH2CH═CH— when A2 is phenyl, benzofused heterocyclyl, heteroaryl, or C3-8cycloalkyl;
alternatively, P is —(CH2)3-6— when A2 is hydrogen, C1-4alkoxy, or C1-4alkoxycarbonyl;
and wherein P is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
A2 is hydrogen, C1-4alkoxy, C1-4alkoxycarbonyl, phenyl, benzofused heterocyclyl, heteroaryl, tetrahydro-pyranyl, piperidinyl, or C3-8cycloalkyl;
wherein phenyl, heteroaryl, the benzo portion of benzofused heterocyclyl, and C3-8cycloalkyl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, halogen, halogenated C1-6alkyl, halogenated C1-6alkoxy, aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, nitro, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkylcarbonylamino, and a non fused C3-6cycloalkyloxy;
such that no more than two substituents on A2 are aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, or a non fused C3-6cycloalkyloxy;
provided that A2 is other than 3,5-di-t-butyl-phenyl;
W is N or C(RW);
wherein RW is H or C1-2alkyl;
Q is selected from the group consisting of (a) to (g), wherein
(a) is —NH(CH2)2—Ar1 wherein Ar1 is pyridinyl optionally substituted one to three C1-4alkyl substituents or a substituent selected from the group consisting of C1-4alkoxy and amino;
provided that when Ar1 is unsubstituted pyridin-3-yl or unsubstituted pyridin-4-yl, and A2 is 4-methoxy-phenyl, A1 is other than unsubstituted phenyl or 3,4-dichloro-phenyl;
(b) is —NHCH(Rz)—Ar2 wherein Rz is H or C1-3alkyl;
Ar2 is pyridinyl, pyrimidinyl, pyrazinyl,
1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
and wherein Ar2 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, trifluoromethyl, hydroxyl-C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, C3-8 cycloalkylamino, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
or Ar2 is optionally substituted with one amino group and three substituents independently selected from the group consisting of C1-4alkyl and C1-4alkoxy;
wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, C1-4alkylthio, hydroxy, a 5 to 6 membered heteroaryl, or a 5 to 6 membered heterocyclyl;
wherein a
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), L1 is —(CH2)2—, and A1 is pyrazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 4-methoxy-phenyl, A2 is other than 2-ethyl-phenyl, 4-ethyl-phenyl, 3-methoxy-phenyl, 3-cyano-phenyl, 3-nitro-phenyl, and 3-trifluoromethyl-4-nitro-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is quinolin-8-yl, benzotriazol-1-yl, 3,5-dimethyl-pyrazolyl, 2-fluoro-phenyl, 2-chloro-phenyl, 2-nitro-phenyl, 2-trifluoromethyl-phenyl, 2-difluoromethoxy-phenyl, 3-difluoromethoxy-phenyl, 2-trifluoromethoxy-phenyl, 2,4-difluoro-phenyl, 2,6-difluoro-phenyl, 2,6-dichloro-phenyl, 2-chloro-4-fluoro-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 4-trifluoromethoxy-phenyl, A2 is other than 4-difluoromethoxy-phenyl;
and, provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 3-nitro-4-methoxy-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
(c) is —CH2NHCH2-Ar3, wherein W is N or CH, and Ar3 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and that the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar3 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(d) is —(CH2)2—Ar4, wherein Ar4 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or nitrogen atom of the 5 to 6 membered heterocyclyl is optionally substituted with a C1-4alkyl substituent;
and wherein pyridin-2-yl and pyridin-3-yl are optionally further substituted with N-pyrrolidinyl, N-piperazinyl, N-piperidinyl, N-morpholinyl, N-thiomorpholinyl, —CH2—O—CH2—PH, and phenyl;
wherein the phenyl substituent of pyridin-2-yl and pyridin-3-yl is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and halogen;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is pyridin-4-yl, 4-C1-6alkyl-phenyl, 3,4-dichloro-phenyl, or 4-methanesulfonyl-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2— or —(CH2)5—, and A1 is methoxy, A2 is other than 4-difluoromethoxy-phenyl or 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is benzotriazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)3—, and A1 is pyrrol-1-yl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2—, and A1 is 4-nitro-phenyl or ethoxy, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-fluoro-phenyl;
provided that when Q is —NHCH2(6-amino-pyridin-2-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-trifluoromethoxy-phenyl;
provided that when Q is —NHCH2(6-methyl-pyridin-2-yl), and A1 is 4-methoxy-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(imidazo[1,2-a]pyridinyl), and A1 is 4-fluoro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(pyridin-4-yl), and A1 is unsubstituted phenyl or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), and A1 is 4-methoxy-phenyl, —P-A2 is other than —(CH2)5-methoxy;
4-position;
wherein Ar4 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(e) is —CH═CH—Ar5;
wherein Ar5 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar5 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(f) is —O—CH(R1)—Ar6 when W is CH;
or, (f) is —S—CH(R1)—Ar6 and W is N or CH;
wherein R1 is hydrogen or C1-4alkyl, and Ar6 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar6 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O—CH(R1)—Ar6, A1 and A2 are 4-methoxy-phenyl, and R1 is hydrogen, Ar6 is other than unsubstituted pyridin-2-yl or 2-amino-pyridin-4-yl;
and
(g) is —X1—(CH(Rx))2—Ar7 when W is CH;
wherein X1 is O or S, Rx is H or C1-4alkyl, and Ar7 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar7 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O(CH2)2—Ar7 and A1 and A2 are 4-methoxy-phenyl, Ar7 is other than unsubstituted pyridin-2-yl or unsubstituted pyridin-3-yl;
wherein a nitrogen atom of Ar1, Ar2, Ar3, Ar4, Ar5, Ar6, and Ar7 is optionally substituted with oxo;
and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof,
said compound of Formula (I) admixed with a veterinarily acceptable carrier, excipient or diluent.

74 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/646,957Filed 28 Dec 2006
Priority: 29 Dec 2005
Published: 20 Nov 2008
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 31/53
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having six-membered rings with three nitrogens as the only ring hetero…
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…

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Application60/754,989Us provisional application · filed 29 Dec 2005
US 2008/0287445 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

The present invention relates to certain novel compounds of Formula (I): and methods for the treatment of prokineticin 2 or prokinetin 2 receptor mediated disorders.

wherein:
A1 is CF3, C1-4alkoxy, aryl, aryloxy, benzofused heterocyclyl, or heteroaryl;
wherein aryl, aryloxy, and heteroaryl are optionally substituted with pyrazol-1-yl or [1,2,3]thiadiazol-4-yl;
or aryl, aryloxy, the benzo portion of benzofused heterocyclyl, and heteroaryl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, halogen, nitro, halogenated C1-6alkyl, halogenated C1-6alkoxy, C1-6alkylthio, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkoxycarbonylamino, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, formyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, aminosulfonyl, C1-6alkylaminosulfonyl, and di(C1-6alkyl)aminosulfonyl;
provided that A1 is other than 3,5-di-t-butyl-phenyl;
L1 is —(CH2)r—, —CH2C2-4alkenyl-, or —CH2CH2X(CH2)s—, wherein L1 is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
and, r is an integer of 1 to 5;
such that r is greater than or equal to 4 when A1 is C1-4alkoxy;
s is an integer of 1 to 3;
X is O or S;
D is —P-A2;
wherein P is —(CH2)1-2— or —CH2CH═CH— when A2 is phenyl, benzofused heterocyclyl, heteroaryl, or C3-8cycloalkyl;
alternatively, P is —(CH2)3-6— when A2 is hydrogen, C1-4alkoxy, or C1-4alkoxycarbonyl;
and wherein P is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C2-6alkenyl, C2-6alkynyl, and halogen;
A2 is hydrogen, C1-4alkoxy, C1-4alkoxycarbonyl, phenyl, benzofused heterocyclyl, heteroaryl, tetrahydro-pyranyl, piperidinyl, or C3-8cycloalkyl;
wherein phenyl, heteroaryl, the benzo portion of benzofused heterocyclyl, and C3-8cycloalkyl are optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, halogen, halogenated C1-6alkyl, halogenated C1-6alkoxy, aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, C1-6alkylthio, C1-6alkylsulfonyl, C1-6alkoxycarbonyl, amino, C1-6alkylamino, di(C1-6alkyl)amino, cyano, hydroxy, nitro, C1-6alkylcarbonyl, C1-6alkylthiocarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, di(C1-6alkyl)aminocarbonyl, C1-6alkylcarbonylamino, and a non fused C3-6cycloalkyloxy;
such that no more than two substituents on A2 are aryl(C1-6)alkoxy, phenyl, N-isoindole-1,3-dione, or a non fused C3-6cycloalkyloxy;
provided that A2 is other than 3,5-di-t-butyl-phenyl;
W is N or C(RW);
wherein RW is H or C1-2alkyl;
Q is selected from the group consisting of (a) to (g), wherein
(a) is —NH(CH2)2—Ar1 wherein Ar1 is pyridinyl optionally substituted one to three C1-4alkyl substituents or a substituent selected from the group consisting of C1-4alkoxy and amino;
provided that when Ar1 is unsubstituted pyridin-3-yl or unsubstituted pyridin-4-yl, and A2 is 4-methoxy-phenyl, A1 is other than unsubstituted phenyl or 3,4-dichloro-phenyl;
(b) is —NHCH(Rz)—Ar2 wherein Rz is H or C1-3alkyl;
Ar2 is pyridinyl, pyrimidinyl, pyrazinyl,
1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
and wherein Ar2 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, trifluoromethyl, hydroxyl-C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, C3-8 cycloalkylamino, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
or Ar2 is optionally substituted with one amino group and three substituents independently selected from the group consisting of C1-4alkyl and C1-4alkoxy;
wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, C1-4alkylthio, hydroxy, a 5 to 6 membered heteroaryl, or a 5 to 6 membered heterocyclyl;
wherein a nitrogen atom of the 5 to 6 membered heterocyclyl is optionally substituted with a C1-4alkyl substituent;
and wherein pyridin-2-yl and pyridin-3-yl are optionally further substituted with N-pyrrolidinyl, N-piperazinyl, N-piperidinyl, N-morpholinyl, N-thiomorpholinyl, —CH2—O—CH2PH, and phenyl;
wherein the phenyl substituent of pyridin-2-yl and pyridin-3-yl is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and halogen;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is pyridin-4-yl, 4-C1-6alkyl-phenyl, 3,4-dichloro-phenyl, or 4-methanesulfonyl-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2— or —(CH2)5—, and A1 is methoxy, A2 is other than 4-difluoromethoxy-phenyl or 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is benzotriazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)3—, and A1 is pyrrol-1-yl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), L1 is —(CH2)2—, and A1 is 4-nitro-phenyl or ethoxy, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(2-amino-pyridin-3-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-fluoro-phenyl;
provided that when Q is —NHCH2(6-amino-pyridin-2-yl), and A1 is 4-fluoro-phenyl, A2 is other than 4-trifluoromethoxy-phenyl;
provided that when Q is —NHCH2(6-methyl-pyridin-2-yl), and A1 is 4-methoxy-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(imidazo[1,2-a]pyridinyl), and A1 is 4-fluoro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(pyridin-4-yl), and A1 is unsubstituted phenyl or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), and A1 is 4-methoxy-phenyl, —P-A2 is other than —(CH2)5-methoxy;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl), L1 is —(CH2)2—, and A1 is pyrazol-1-yl, A2 is other than 4-difluoromethoxy-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 4-methoxy-phenyl, A2 is other than 2-ethyl-phenyl, 4-ethyl-phenyl, 3-methoxy-phenyl, 3-cyano-phenyl, 3-nitro-phenyl, and 3-trifluoromethyl-4-nitro-phenyl;
provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is quinolin-8-yl, benzotriazol-1-yl, 3,5-dimethyl-pyrazolyl, 2-fluoro-phenyl, 2-chloro-phenyl, 2-nitro-phenyl, 2-trifluoromethyl-phenyl, 2-difluoromethoxy-phenyl, 3-difluoromethoxy-phenyl, 2-trifluoromethoxy-phenyl, 2,4-difluoro-phenyl, 2,6-difluoro-phenyl, 2,6-dichloro-phenyl, 2-chloro-4-fluoro-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 4-trifluoromethoxy-phenyl, A2 is other than 4-difluoromethoxy-phenyl;
and, provided that when Q is —NHCH2(4,6-dimethyl-pyridin-3-yl) and A1 is 3-nitro-4-methoxy-phenyl, 2,6-difluoro-4-methoxy-phenyl, or 3,4-dichloro-phenyl, A2 is other than 4-methoxy-phenyl;
(c) is —CH2NHCH2—Ar3, wherein W is N or CH, and Ar3 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and that the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar3 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, and di(C1-6alkyl)amino;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(d) is —(CH2)2—Ar4, wherein Ar4 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar4 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(e) is —CH═CH—Ar5;
wherein Ar5 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl;
such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, .3, or 4-position;
wherein Ar5 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
(f) is —O—CH(R1)—Ar6 when W is CH;
or, (f) is —S—CH(R1)—Ar6 and W is N or CH;
wherein R1 is hydrogen or C1-4alkyl, and Ar6 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar6 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O—CH(R1)—Ar6, A1 and A2 are 4-methoxy-phenyl, and R1 is hydrogen, Ar6 is other than unsubstituted pyridin-2-yl or 2-amino-pyridin-4-yl;
and
(g) is —X1—(CH(Rx))2—Ar7 when W is CH;
wherein X1 is O or S, Rx is H or C1-4alkyl, and Ar7 is pyridinyl, pyrimidinyl, 1,2,3,4-tetrahydro-[1,8]naphthyridinyl, imidazo[1,2-a]pyridinyl, or quinolinyl such that the point of attachment to 1,2,3,4-tetrahydro-[1,8]naphthyridinyl is at the 6 or 7 position, and the point of attachment to quinolinyl is at the 2, 3, or 4-position;
wherein Ar7 is optionally substituted with one to three substituents independently selected from the group consisting of C1-4alkyl, amino(C1-4)alkyl, (C1-4alkyl)amino-(C1-4)alkyl, di(C1-4alkyl)amino-(C1-4)alkyl, C1-4alkoxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, halogen, and aminocarbonyl;
and wherein the C1-6alkyl group of (C1-6alkyl)amino and di(C1-6alkyl)amino is optionally substituted with amino, (C1-4alkyl)amino, di(C1-4alkyl)amino, C3-8cycloalkylamino, C1-4alkoxy, or hydroxy;
provided that when Q is —O(CH2)2—Ar7 and A1 and A2 are 4-methoxy-phenyl, Ar7 is other than unsubstituted pyridin-2-yl or unsubstituted pyridin-3-yl;
wherein a nitrogen atom of Ar1, Ar2, Ar3, Ar4, Ar5, Ar6, and Ar7 is optionally substituted with oxo;
and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof.

72 more elements

Facts

Application

11/646,957Filed 28 Dec 2006

Priority

29 Dec 2005

Published

20 Nov 2008

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 codes

A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 31/53
Having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins: having six-membered rings with three nitrogens as the only ring hetero…
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…