US 2007/0191391 A1Published application

Urotensin II receptor antagonists

OwnerBruce Maryanoff, William Kinney +5inventors

InventorsBruce Maryanoff, William Kinney, Edward Lawson, Diane Luci, Nikolay Marchenko, Sergey Sviridov, Shyamali Ghosh

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Abstract

The invention is directed to Urotensin II antagonists. More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating Urotensin-II mediated disorders. Pharmaceutical and veterinary compositions and methods of treating cardiovascular disorders and various other disease states or conditions using compounds of the invention are also described.

Claims39

Dependent claims

A compound of Formula (I):

wherein:
when A is present, then G is selected from hydrogen, C1-8alkyl, C2-8alkenyl, C3-14cycloalkyl or a —C[(R1)(R11)]-L-D moiety:
wherein C1-8alkyl is optionally substituted with one, two or three fluoro substitutents, and
wherein C3-14cycloalkyl is optionally substituted with one, two or three C1-3alkyl substitutents;
or,
when A is absent and R2 is other than benzyloxymethyl, then G is C1-8alkoxy or heterocyclyloxy,
wherein C1-8alkoxy is substituted with one of amino, (C1-8alkyl)amino, di(C1-8alkyl)amino, (benzyl)amino or [(benzyl)(C1-4alkyl)]amino, and
wherein heterocyclyloxy is optionally substituted on heterocyclyl with one, two or three C1-3alkyl substitutents;
R1 is selected from the group consisting of hydrogen, C1-8alkyl, C2-8alkenyl, and C2-8alkynyl;
R11 is selected from the group consisting of hydrogen, C1-8alkyl and cyclopropyl;
L is absent or C1-4alkylene;
D is aryl (other than naphthalen-2-yl), C3-14cycloalkyl, C5-14cycloalkenyl, heterocyclyl, or heteroaryl,
wherein aryl and heteroaryl are optionally substituted with one, two, three or four substitutents independently selected from the group consisting of C1-3alkyl, C1-3alkoxy, C2-8alkenyl, C2-3alkenyloxy, hydroxy, C1-3alkylthio, fluoro, chloro, cyano, C1-3alkylcarbonyl, (C1-3alkylcarbonyl)amino, (C1-3alkyl)amino, di(C1-3alkyl)amino and C3-14cycloalkyl, wherein C3-14cycloalkyl is optionally substituted with one, two, three or four C1-3alkyl substitutents,
provided that D is other than 2-hydroxy-5-chloro-phenyl, 3-methoxy-phenyl, 4-ethyl-phenyl, 6,6-dimethyl-bicyclo[3.1.1]hept-2-en-2-yl-methyl, cyclohex-3-phenyl, 2,6-dichloro-phenyl and 2-chloro-4-fluoro-phenyl;
A is an optionally present biradical selected from the group consisting of a-1, optionally unsaturated a-2, a-3, a-4, optionally unsaturated a-5 and a-6,
wherein, the lower portion of A is attached, relative to the nitrogen atom of Formula (I), to the 3 or 4 position on the benzene ring portion of Formula (I);
wherein a-1, a-2, a-3, a-4 and a-5 are optionally substituted with one to two C1-4alkyl substitutents;
provided that A is other than cis-(1,2)-cyclohexyldiamino;
R4 is hydrogen or C1-8alkyl;
L2 is absent or —C(R2)(R5)—(CR6R7)r—, wherein r is 0, 1 or 2;
and wherein R5, R6, and R7 are independently hydrogen or C1-3alkyl;
provided that L2 is other than —CH(R-carboxymethyl);
R2 is selected from the group consisting of hydrogen, a heteroaryl that is not fused to another ring, phenyl, and C1-6alkyl, wherein phenyl is optionally substituted with (R200—C1-6alkyl)amino, or [(hydroxysulfonyl)(Ra)]amino, and
wherein C1-6alkyl is optionally substituted with carboxy, hydroxy, R200, NRaRb, C1-6alkoxy, R200—C1-6alkoxy, R200-oxy, aminocarbonyl, carboxy-C1-6alkoxy, aminocarbonyl-C1-6alkoxy, (C1-6alkyl)aminocarbonyl, di(C1-6alkyl)aminocarbonyl, [(R200—C1-6alkyl)(Ra)]amino, (C1-6alkylcarbonyl)amino, (trihalo-C1-4alkylcarbonyl)amino, (R200—C1-16alkylcarbonyl)amino, (C1-6alkoxycarbonyl)amino, (R200—C1-16alkoxycarbonyl)amino, (C1-6alkoxy-C1-6alkylcarbonyl)amino, (R200-carbonyl)amino, (amino-C1-6alkylcarbonyl)amino, [(C1-6alkyl)amino-C1-16alkylcarbonyl]amino, [di(C1-6alkyl)amino-C1-6alkylcarbonyl]amino, (C1-6alkylcarbonyl-acetonitrile-carbonyl)amino, ureido, thioureido, acetamidino, guanidino, {[(R200)(Ra)]aminocarbonyl-(Rc)}amino, [(R200-oxycarbonyl)(Ra)]amino, [(R200)(Ra)]aminocarbonyloxy, aminosulfonyl, C1-6alkylsulfonyl, (C1-6alkylsulfonyl)amino, (R200—C1-6alkylsulfonyl)amino, (R200—C2-6alkenylsulfonyl)amino, (C1-6alkylsulfonyl-C1-6alkylsulfonyl)amino, R200-sulfonyloxy, aminosulfonyloxy, (C1-6alkyl)aminosulfonyloxy, di(C1-6alkyl)aminosulfonyloxy, aminosulfonylamino, (C1-6alkyl)aminosulfonylamino, [di(C1-6alkyl)aminosulfonyl]amino, [(hydroxysulfonyl)(Ra)]amino, [(R200-oxysulfonyl)(Ra)]amino, [(R200-sulfonyl)(Ra)]amino, [(R200)(Ra)]aminosulfonyloxy, or ({[(R200)(Ra)]aminosulfonyl}(Rc))amino;
Ra and Rc are independently selected from the group consisting of hydrogen and C1-6alkyl;
and Rb is hydrogen, C1-6alkyl, C1-10aryl, heteroaryl, C3-8cycloalkyl, or heterocyclyl;
R200 is C1-10aryl, heteroaryl, C3-8cycloalkyl, or heterocyclyl, each optionally substituted with one, two or three substitutents independently selected from the group consisting of C1-4alkyl, trihalo-C1-4alkyl, C1-4alkoxy, trihalo-C1-4alkoxy, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, (C1-6alkylcarbonyl)amino, C1-6alkylsulfonyl, hydroxysulfonyl, aminosulfonyl, chloro, fluoro, bromo, aryl, heteroaryl, aryl-C1-6alkyl, aryl-sulfonyl and heteroaryl-sulfonyl,
wherein heterocyclyl is optionally substituted with one, two or three oxo substitutents;
B is C1-10aryl, tetralinyl, indanyl, or a heteroaryl selected from the group consisting of pyridin-2-yl, pyridin-4-yl, pyrazol-4-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazin-2-yl, imidazol-1-yl, thien-2-yl, isoquinolinyl, indolyl, quinolinyl, and thiazol-5-yl,
wherein B is optionally substituted with one, two or three substitutents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, fluorinated (C1-4)alkoxy, halogen, cyano, hydroxy, aminocarbonyl, (C1-4)alkylaminocarbonyl, di(C1-4)alkylaminocarbonyl, aminosulfonyl, (C1-4)alkylaminosulfonyl, di(C1-4)alkylaminosulfonyl, hydroxysulfonyl, aminosulfonylamino, (C1-4)alkylaminosulfonylamino, di(C1-4)alkylaminosulfonylamino, aminosulfonyloxy, (C1-4)alkylaminosulfonyloxy, and di(C1-4)alkylaminosulfonyloxy,
provided that when B is selected from the group consisting of C6-10aryl, tetralinyl, indanyl, thien-2-yl, and indolyl, then B is independently substituted with two to three substitutents selected from the group consisting of C1-3alkoxy and hydroxy,
provided that, when B is phenyl substituted at the 3,4-, 3,5- or 4,5-positions with an unbranched C1-3alkoxy substitutent at each position, then phenyl may be further optionally substituted at a remaining open 3-, 4-, or 5-position with an additional C1-3alkoxy or hydroxy substitutent, and
provided that B is other than 3-hydroxy-4-methoxy-phenyl and 3-(n-propyloxy)-4-methoxy-phenyl;
E is hydrogen, halogen, C1-3alkoxy, C2-5alkyl-RE, or —CH═CH—C0-3alkyl-RE;
wherein RE is selected from the group consisting of carboxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, aminocarbonyl, (C1-6alkyl)aminocarbonyl, di(C1-6alkyl)aminocarbonyl, (C1-6alkyl)carbonylamino, C1-6alkoxycarbonylamino, aminocarbonyl(C1-6)alkoxy, ureido, thioureido, aminosulfonyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, aminosulfonyloxy, (C1-6alkyl)aminosulfonyloxy, di(C1-6alkyl)aminosulfonyloxy, aminosulfonylamino, (C1-6alkyl)aminosulfonylamino, di(C1-6alkyl)aminosulfonylamino, (R200)(Ra)aminocarbonyl-(Rc)amino, R200carbonylamino, R200oxycarbonyl-(Ra)amino, (R200)(Ra)aminocarbonyloxy, R200oxysulfonyl-(Ra)amino, R200sulfonyl-(Ra)amino, (R200)(Ra)aminosulfonyloxy, and (R200)(Ra)aminosulfonyl-(Rc)amino;
X and Y are independently O or S;
and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof.

34 more elements

A compound selected from the group consisting of:

2-(3,4-dimethoxy-benzyl)-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-[1-(3,4-dimethoxy-phenyl)-ethyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-[(S)-1-(3,4-dimethoxy-phenyl)-ethyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
(R)-2-[1-(3,4-dimethoxy-phenyl)-ethyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-(4-benzyl-piperazin-1-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-(8-benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
2-[1-(3,4-dimethoxy-phenyl)-propyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-(8-benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-7-chloro-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
4-chloro-2-(3,4-dimethoxy-benzyl)-7-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-(4-benzyl-piperazin-1-yl)-2-(5,6-dimethoxy-indan-1-yl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(4-fluoro-benzyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(1-phenyl-propyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(1S)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-(4-hydroxy-3-methoxy-benzyl)-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-[4-(2,6-difluoro-benzyl)-piperazin-1-yl]-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(3-fluoro-benzyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-(4-ethoxy-3-methoxy-benzyl)-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-(1-benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-(4-indan-1-yl-piperazin-1-yl)-isoindole-1,3-dione,
2-(3-ethoxy-4-methoxy-benzyl)-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-(4-phenethyl-piperazin-1-yl)-isoindole-1,3-dione
4-(4-benzyl-piperazin-1-yl)-2-(1,3,5-trimethyl-1H-pyrazol-4-ylmethyl)-isoindole-1,3-dione,
4-[4-(2,4-difluoro-benzyl)-piperazin-1-yl]-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
4-(8-benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-2-[2-(3,4-dimethoxy-phenyl)-ethyl]-isoindole-1,3-dione,
4-(8-benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-2-(3,4,5-trimethoxy-benzyl)-isoindole-1,3-dione,
4-[4-(cyclopropyl-phenyl-methyl)-piperazin-1-yl]-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(1-methyl-1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-[4-(2,5-difluoro-benzyl)-piperazin-1-yl]-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
(S)-3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propionic acid,
4-[4-(2-chloro-benzyl)-piperazin-1-yl]-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[8-(1-phenyl-ethyl)-3,8-diaza-bicyclo[3.2.1]oct-3-yl]-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(2-methyl-benzyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-(4-benzyl-piperazin-1-yl)-2-(3,4,5-trimethoxy-benzyl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(1-phenyl-prop-2-ynyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(3-methyl-benzyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-(1R,2R)-(2-benzylamino-cyclohexylamino)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
2-{4-[2-(3,4-dimethoxy-benzyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]-piperazin-1-ylmethyl}-benzonitrile,
4-(8-benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-2-pyridin-4-ylmethyl-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(4-methyl-benzyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-(3-methoxy-4-propoxy-benzyl)-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
(3R,5S)-4-(4-benzyl-3,5-dimethyl-piperazin-1-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
4-(4-benzyl-piperazin-1-yl)-2-(2-pyridin-4-yl-ethyl)-isoindole-1,3-dione,
4-[4-(3-chloro-benzyl)-piperazin-1-yl]-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
4-(8-benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-2-(3,5-dimethoxy-benzyl)-isoindole-1,3-dione,
4-[4-(3,5-difluoro-benzyl)-piperazin-1-yl]-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
4-(4-benzyl-piperazin-1-yl)-2-(3-imidazol-1-yl-propyl)-isoindole-1,3-dione,
4-(2-benzylamino-ethylamino)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
2-[(3,4-dimethoxy-phenyl)-phenyl-methyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-(8-benzyl-8-aza-bicyclo[3.2.1]oct-2-en-3-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
(3R,5S)-2-(3,4-dimethoxy-benzyl)-4-[3,5-dimethyl-4-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-(4-isopropyl-piperazin-1-yl)-2-(3,4,5-trimethoxy-benzyl)-isoindole-1,3-dione,
4-[2-(benzyl-methyl-amino)-ethoxy]-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
4-(2-benzylamino-ethoxy)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
4-(4-benzyl-piperazin-1-yl)-2-(1,5-dimethyl-1H-pyrazol-4-ylmethyl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(3,4-dimethoxy-benzyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-[4-(4-chloro-benzyl)-piperazin-1-yl]-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
4-(4-benzyl-piperazin-1-yl)-2-(2-methoxy-pyridin-4-ylmethyl)-isoindole-1,3-dione,
4-(8-benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-2-pyridin-2-ylmethyl-isoindole-1,3-dione,
4-(4-isobutyl-piperazin-1-yl)-2-(3,4,5-trimethoxy-benzyl)-isoindole-1,3-dione,
4-(8-benzyl-3,8-diaza-bicyclo[3.2.1]oct-3-yl)-2-(3,4-dimethoxy-phenyl)-isoindole-1,3-dione
2-(3,4-dimethoxy-benzyl)-4-(2-methanesulfonyl-vinyl)-7-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-[1-(3,4-dimethoxy-phenyl)-2-dimethylamino-ethyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-[2-amino-1-(3,4-dimethoxy-phenyl)-ethyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-carbamic acid tert-butyl ester,
2-[4-amino-1-(3,4-dimethoxy-phenyl)-butyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-methanesulfonamide,
thiophene-2-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(5-(3,4-dimethoxy-phenyl)-5-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-pentyl)-carbamic acid tert-butyl ester,
2-[5-amino-1-(3,4-dimethoxy-phenyl)-pentyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
5-chloro-thiophene-2-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(2-(3,4-dimethoxy-phenyl)-2-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-ethyl)-carbamic acid tert-butyl ester,
(3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-carbamic acid tert-butyl ester,
thiophene-2-sulfonic acid (2-(3,4-dimethoxy-phenyl)-2-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-ethyl)-amide,
thiophene-2-sulfonic acid (3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-amide,
4-(1-benzyl-piperidin-4-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(5-methyl-furan-2-ylmethyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-(4-furan-3-ylmethyl-piperazin-1-yl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-(4-pyridin-3-ylmethyl-piperazin-1-yl)-isoindole-1,3-dione,
4-(4-cyclopentylmethyl-piperazin-1-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-(4-thiophen-2-ylmethyl-piperazin-1-yl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-(4-isobutyl-piperazin-1-yl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-(4-thiophen-3-ylmethyl-piperazin-1-yl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-(4-pyridin-2-ylmethyl-piperazin-1-yl)-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-4-[4-(2-hydroxy-benzyl)-piperazin-1-yl]-isoindole-1,3-dione,
(E)-2-(3,4-dimethoxy-benzyl)-4-[4-(2-methyl-but-2-phenyl)-piperazin-1-yl]-isoindole-1,3-dione,
4-(4-adamantan-2-yl-piperazin-1-yl)-2-(3,4-dimethoxy-benzyl)-isoindole-1,3-dione,
5-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butylsulfamoyl)-4-methoxy-thiophene-3-carboxylic acid methyl ester,
5-methyl-2-trifluoromethyl-furan-3-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
5-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butylsulfamoyl)-furan-2-carboxylic acid methyl ester,
1,3,5-trimethyl-1H-pyrazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
4-benzenesulfonyl-thiophene-2-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
6-chloro-imidazo[2,1-b]thiazole-5-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
3-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butylsulfamoyl)-thiophene-2-carboxylic acid methyl ester,
5-isoxazol-3-yl-thiophene-2-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-benzenesulfonamide,
N-[5-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butylsulfamoyl)-4-methyl-thiazol-2-yl]-acetamide,
1-methyl-1H-imidazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
2,5-dimethyl-furan-3-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
5-bromo-thiophene-2-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
N-(2-(3,4-dimethoxy-phenyl)-2-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-ethyl)-2-pyridin-4-yl-acetamide,
N-(3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-2-pyridin-4-yl-acetamide,
thiophene-2-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
thiophene-3-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
pyridine-3-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
pyridine-2-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
5-methyl-isoxazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
quinoline-8-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-C-methanesulfonyl-methanesulfonamide,
2-phenyl-ethenesulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
3,5-dimethyl-isoxazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
2,5-dichloro-thiophene-3-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
1,2-dimethyl-1H-imidazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
N′-[(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)]-N,N-dimethyl-sulfamide,
benzo[b]thiophene-3-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-C-phenyl-methanesulfonamide,
(R)-thiophene-2-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(S)-thiophene-2-sulfonic acid 4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
1-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-3-thiophen-2-yl-urea,
1-(3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-3-thiophen-2-yl-urea,
N′-[(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)]-sulfamide,
2-[1,2-bis-(3,4-dimethoxy-phenyl)-ethyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
(R)-2,4-dimethyl-thiazole-5-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-3,5-dimethyl-1H-pyrazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-5-methyl-thiophene-2-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-2,3-dimethyl-3H-imidazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1,3-dimethyl-1H-pyrazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-sulfamic acid,
(R)-N-[5-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butylsulfamoyl)-4-methyl-thiazol-2-yl]-acetamide,
(R)-2,5-dimethyl-thiophene-3-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1,5-dimethyl-1H-pyrazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1,1-dioxo-tetrahydro-1λ6-thiophene-3-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1-ethyl-1H-pyrazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-(1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1-methyl-3-trifluoromethyl-1H-pyrazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1-methyl-1H-pyrazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-5-fluoro-3-methyl-benzo[b]thiophene-2-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-5-methyl-isoxazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-3,5-dimethyl-isoxazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1,2-dimethyl-1H-imidazole-4-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-N′-[(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)]-sulfamide,
(R)-2-[1-(3,4-dimethoxy-phenyl)-4-(pyridin-2-ylamino)-butyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-2-dimethylamino-acetamide,
(R)-5-methyl-isoxazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-2-[1-(3,4-dimethoxy-phenyl)-4-(pyrimidin-2-ylamino)-butyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-guanidine,
(R)-1-methyl-1H-pyrrole-2-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1-methyl-5-sulfamoyl-1H-pyrrole-2-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1-acetyl-pyrrolidine-2-carboxylic acid (R)-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-pyridine-2-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-nicotinamide,
(R)-3-methyl-3H-imidazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1-methyl-1H-imidazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-isonicotinamide,
(R)-tetrahydro-furan-2-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-2-methyl-thiazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-5-methanesulfonyl-thiophene-2-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-3-methyl-isoxazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-5-methyl-isoxazole-3-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-pyridazine-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1-methyl-1H-imidazole-2-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-4,5-dimethyl-furan-2-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-thiazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-3,5-dimethyl-isoxazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-2-[4-(4,5-dihydro-1H-pyrrol-2-ylamino)-1-(3,4-dimethoxy-phenyl)-butyl]-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-acetamidine,
(R)-thiophene-2-sulfonic acid [4-(3,4-dimethoxy-phenyl)-4-(1,3-dioxo-4-piperazin-1-yl-1,3-dihydro-isoindol-2-yl)-butyl]-amide,
(R)-thiophene-2-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[4-(4-ethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
(R)-thiophene-2-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[4-(4-methyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
(R)-thiophene-2-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[4-(4-furan-3-ylmethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
(R)-thiophene-2-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[1,3-dioxo-4-(4-pyridin-3-ylmethyl-piperazin-1-yl)-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
(R)-thiophene-2-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[1,3-dioxo-4-(4-thiophen-3-ylmethyl-piperazin-1-yl)-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
(R)-tetrahydro-furan-3-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-isobutyramide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-2-methoxy-acetamide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-butyramide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-3-methoxy-propionamide,
(R)-cyclobutanecarboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-cyclopentanecarboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-propionamide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-3-methyl-butyramide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-2-ethoxy-acetamide,
(R)-5-chloro-1-methyl-1H-pyrazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-1,3,5-trimethyl-1H-pyrazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-2,2-dimethyl-propionamide,
(R)-furan-3-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-isoxazole-5-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-2,5-dimethyl-1H-pyrrole-3-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-3-ethoxy-propionamide,
(R)-1H-pyrazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(S)-1-methyl-pyrrolidine-2-carboxylic acid (R)-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-thiophene-2-sulfonic acid [4-[4-(4-cyclobutyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-4-(3,4-dimethoxy-phenyl)-butyl]-amide,
(R)-thiophene-2-sulfonic acid [4-[4-(4-cyclopentyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-4-(3,4-dimethoxy-phenyl)-butyl]-amide,
(R)-thiophene-2-sulfonic acid [4-[4-(4-allyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-4-(3,4-dimethoxy-phenyl)-butyl]-amide,
(R)-thiophene-2-sulfonic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(2,2,2-trifluoro-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-thiophene-2-sulfonic acid [4-[4-(4-cyclohexyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-4-(3,4-dimethoxy-phenyl)-butyl]-amide,
(R)-{4-(3,4-dimethoxy-phenyl)-4-[4-(4-ethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-carbamic acid tert-butyl ester,
(R)-thiophene-2-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[4-(4-isopropyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
(R)-2-cyano-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-3-oxo-butyramide,
(R)-N-{4-(3,4-dimethoxy-phenyl)-4-[4-(1-methyl-pyrrolidin-3-yloxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-isobutyramide,
(R)-2-[4-benzyloxy-1-(3,4-dimethoxy-phenyl)-butyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione,
(R)-cyclobutanecarboxylic acid {4-(3,4-dimethoxy-phenyl)-4-[4-(4-ethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
(R)-1,2-dimethyl-1H-imidazole-4-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[4-(4-ethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
(R)-1,3,5-trimethyl-1H-pyrazole-4-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[4-(4-ethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
(R)-N-{4-(3,4-dimethoxy-phenyl)-4-[4-(1-methyl-piperidin-4-yloxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-isobutyramide,
(R)-2-[1-(3,4-dimethoxy-phenyl)-4-hydroxy-butyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione,
(R)-2-[1-(3,4-dimethoxy-phenyl)-4-ethoxy-butyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione,
(R)-thiophene-2-sulfonic acid 4-(3,4-dimethoxy-phenyl)-4-[4-(4-ethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl ester,
(R)-dimethyl-sulfamic acid 4-(3,4-dimethoxy-phenyl)-4-[4-(4-ethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl ester,
(R)-2-[1-(3,4-dimethoxy-phenyl)-4-isobutoxy-butyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione,
(R)-2-methyl-thiazole-4-carboxylic acid (3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-amide,
(R)-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-2,2,2-trifluoro-acetamide,
(R)-2-tert-butoxy-N-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-acetamide,
(R)-2-[1-(3,4-dimethoxy-phenyl)-4-(thiophen-2-ylmethoxy)-butyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione,
(R)-3,5-dimethyl-1H-pyrazole-4-carboxylic acid (4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-amide,
(R)-(3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-carbamic acid benzyl ester,
(R)-5-methyl-isoxazole-4-carboxylic acid (3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-amide,
(R)-{4-(3,4-dimethoxy-phenyl)-4-[4-(4-ethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butoxy}-acetic acid,
(R)-1,2-dimethyl-1H-imidazole-4-sulfonic acid (3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-amide,
(R)-(3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-sulfamic acid,
(R)-N-(3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-isonicotinamide,
(R)-N-(3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-C-phenyl-methanesulfonamide,
(R)-3,5-dimethyl-1H-pyrazole-4-sulfonic acid (3-(3,4-dimethoxy-phenyl)-3-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-propyl)-amide,
(R)-thiophene-2-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[4-(3-dimethylamino-propoxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
2-(2-bromo-4,5-dimethoxy-benzyl)-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
2-(3,4-dimethoxy-benzyl)-5-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-isoindole-1,3-dione,
(R)-2-[4-(2,6-difluoro-benzyloxy)-1-(3,4-dimethoxy-phenyl)-butyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione,
(R)-(4-(3,4-dimethoxy-phenyl)-4-{1,3-dioxo-4-[4-(1R)-(1-phenyl-ethyl)-piperazin-1-yl]-1,3-dihydro-isoindol-2-yl}-butyl)-methyl-sulfamic acid,
(R)-thiophene-2-sulfonic acid {4-(3,4-dimethoxy-phenyl)-4-[4-(2-dimethylamino-ethoxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-butyl}-amide,
2-[(3-benzylamino-phenyl)-(3,4-dimethoxy-phenyl)-methyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione,
(3-{(3,4-dimethoxy-phenyl)-[4-(4-ethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-methyl}-phenyl)-sulfamic acid,
2-[2-(1-benzyl-piperidin-4-yl)-1-(3,4-dimethoxy-phenyl)-ethyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione,
4-{2-(3,4-dimethoxy-phenyl)-2-[4-(4-ethyl-piperazin-1-yl)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-ethyl}-piperidine-1-sulfonic acid,
2-{1-(3,4-dimethoxy-phenyl)-2-[1-(thiophene-2-sulfonyl)-piperidin-4-yl]-ethyl}-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione,
(R)-2-[1-(3,4-dimethoxy-phenyl)-4-imidazol-1-yl-butyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione,
(R)-2-[4-(benzyl-methyl-amino)-1-(3,4-dimethoxy-phenyl)-butyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione, and
(R)-2-[4-benzoimidazol-1-yl-1-(3,4-dimethoxy-phenyl)-butyl]-4-(4-ethyl-piperazin-1-yl)-isoindole-1,3-dione.

234 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/651,848Filed 10 Jan 2007
Priority: 10 Jan 2006
Published: 16 Aug 2007
Term ends: Not estimatedThe source records don’t support an estimate.

Classification36 codes

C07D 209/48
Iso-indoles; Hydrogenated iso-indoles: with oxygen atoms in positions 1 and 3, e.g. phthalimide
A61P 1/12
Drugs for disorders of the alimentary tract or the digestive system: antidiarrhoeals
A61P 1/18
Drugs for disorders of the alimentary tract or the digestive system: for pancreatic disorders, e.g. pancreatic enzymes
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics

Family

Application60/757,692Us provisional application · filed 10 Jan 2006
US 7,915,260 B2Related patent
US 2007/0191391 A1This patent

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

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Abstract

A compound of Formula (I):

wherein:
when A is present, then G is selected from hydrogen, C1-8alkyl, C2-8alkenyl, C3-14cycloalkyl or a —C[(R1)(R11)]-L-D moiety:
wherein C1-8alkyl is optionally substituted with one, two or three fluoro substitutents, and
wherein C3-14cycloalkyl is optionally substituted with one, two or three C1-3alkyl substitutents;
or,
when A is absent and R2 is other than benzyloxymethyl, then G is C1-8alkoxy or heterocyclyloxy,
wherein C1-8alkoxy is substituted with one of amino, (C1-8alkyl)amino, di(C1-8alkyl)amino, (benzyl)amino or [(benzyl)(C1-4alkyl)]amino, and
wherein heterocyclyloxy is optionally substituted on heterocyclyl with one, two or three C1-3alkyl substitutents;
R1 is selected from the group consisting of hydrogen, C1-8alkyl, C2-8alkenyl, and C2-8alkynyl;
R11 is selected from the group consisting of hydrogen, C1-8alkyl and cyclopropyl;
L is absent or C1-4alkylene;
D is aryl (other than naphthalen-2-yl), C3-14cycloalkyl, C5-14cycloalkenyl, heterocyclyl, or heteroaryl,
wherein aryl and heteroaryl are optionally substituted with one, two, three or four substitutents independently selected from the group consisting of C1-3alkyl, C1-3alkoxy, C2-8alkenyl, C2-3alkenyloxy, hydroxy, C1-3alkylthio, fluoro, chloro, cyano, C1-3alkylcarbonyl, (C1-3alkylcarbonyl)amino, (C1-3alkyl)amino, di(C1-3alkyl)amino and C3-14cycloalkyl, wherein C3-14cycloalkyl is optionally substituted with one, two, three or four C1-3alkyl substitutents,
provided that D is other than 2-hydroxy-5-chloro-phenyl, 3-methoxy-phenyl, 4-ethyl-phenyl, 6,6-dimethyl-bicyclo[3.1.1]hept-2-en-2-yl-methyl, cyclohex-3-phenyl, 2,6-dichloro-phenyl and 2-chloro-4-fluoro-phenyl;
A is an optionally present biradical selected from the group consisting of a-1, optionally unsaturated a-2, a-3, a-4, optionally unsaturated a-5 and a-6,
wherein, the lower portion of A is attached, relative to the nitrogen atom of Formula (I), to the 3 or 4 position on the benzene ring portion of Formula (I);
wherein a-1, a-2, a-3, a-4 and a-5 are optionally substituted with one to two C1-4alkyl substitutents;
provided that A is other than cis-(1,2)-cyclohexyldiamino;
R4 is hydrogen or C1-8alkyl;
L2 is absent or —C(R2)(R5)—(CR6R7)r—, wherein r is 0, 1 or 2;
and wherein R5, R6, and R7 are independently hydrogen or C1-3alkyl;
provided that L2 is other than —CH(R-carboxymethyl);
R2 is selected from the group consisting of hydrogen, a heteroaryl that is not fused to another ring, phenyl, and C1-6alkyl, wherein phenyl is optionally substituted with (R200—C1-6alkyl)amino, or [(hydroxysulfonyl)(Ra)]amino, and
wherein C1-6alkyl is optionally substituted with carboxy, hydroxy, R200, NRaRb, C1-6alkoxy, R200—C1-6alkoxy, R200-oxy, aminocarbonyl, carboxy-C1-6alkoxy, aminocarbonyl-C1-6alkoxy, (C1-6alkyl)aminocarbonyl, di(C1-6alkyl)aminocarbonyl, [(R200—C1-6alkyl)(Ra)]amino, (C1-6alkylcarbonyl)amino, (trihalo-C1-4alkylcarbonyl)amino, (R200—C1-16alkylcarbonyl)amino, (C1-6alkoxycarbonyl)amino, (R200—C1-16alkoxycarbonyl)amino, (C1-6alkoxy-C1-6alkylcarbonyl)amino, (R200-carbonyl)amino, (amino-C1-6alkylcarbonyl)amino, [(C1-6alkyl)amino-C1-16alkylcarbonyl]amino, [di(C1-6alkyl)amino-C1-6alkylcarbonyl]amino, (C1-6alkylcarbonyl-acetonitrile-carbonyl)amino, ureido, thioureido, acetamidino, guanidino, {[(R200)(Ra)]aminocarbonyl-(Rc)}amino, [(R200-oxycarbonyl)(Ra)]amino, [(R200)(Ra)]aminocarbonyloxy, aminosulfonyl, C1-6alkylsulfonyl, (C1-6alkylsulfonyl)amino, (R200—C1-6alkylsulfonyl)amino, (R200—C2-6alkenylsulfonyl)amino, (C1-6alkylsulfonyl-C1-6alkylsulfonyl)amino, R200-sulfonyloxy, aminosulfonyloxy, (C1-6alkyl)aminosulfonyloxy, di(C1-6alkyl)aminosulfonyloxy, aminosulfonylamino, (C1-6alkyl)aminosulfonylamino, [di(C1-6alkyl)aminosulfonyl]amino, [(hydroxysulfonyl)(Ra)]amino, [(R200-oxysulfonyl)(Ra)]amino, [(R200-sulfonyl)(Ra)]amino, [(R200)(Ra)]aminosulfonyloxy, or ({[(R200)(Ra)]aminosulfonyl}(Rc))amino;
Ra and Rc are independently selected from the group consisting of hydrogen and C1-6alkyl;
and Rb is hydrogen, C1-6alkyl, C1-10aryl, heteroaryl, C3-8cycloalkyl, or heterocyclyl;
R200 is C1-10aryl, heteroaryl, C3-8cycloalkyl, or heterocyclyl, each optionally substituted with one, two or three substitutents independently selected from the group consisting of C1-4alkyl, trihalo-C1-4alkyl, C1-4alkoxy, trihalo-C1-4alkoxy, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, (C1-6alkylcarbonyl)amino, C1-6alkylsulfonyl, hydroxysulfonyl, aminosulfonyl, chloro, fluoro, bromo, aryl, heteroaryl, aryl-C1-6alkyl, aryl-sulfonyl and heteroaryl-sulfonyl,
wherein heterocyclyl is optionally substituted with one, two or three oxo substitutents;
B is C1-10aryl, tetralinyl, indanyl, or a heteroaryl selected from the group consisting of pyridin-2-yl, pyridin-4-yl, pyrazol-4-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyrazin-2-yl, imidazol-1-yl, thien-2-yl, isoquinolinyl, indolyl, quinolinyl, and thiazol-5-yl,
wherein B is optionally substituted with one, two or three substitutents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, fluorinated (C1-4)alkoxy, halogen, cyano, hydroxy, aminocarbonyl, (C1-4)alkylaminocarbonyl, di(C1-4)alkylaminocarbonyl, aminosulfonyl, (C1-4)alkylaminosulfonyl, di(C1-4)alkylaminosulfonyl, hydroxysulfonyl, aminosulfonylamino, (C1-4)alkylaminosulfonylamino, di(C1-4)alkylaminosulfonylamino, aminosulfonyloxy, (C1-4)alkylaminosulfonyloxy, and di(C1-4)alkylaminosulfonyloxy,
provided that when B is selected from the group consisting of C6-10aryl, tetralinyl, indanyl, thien-2-yl, and indolyl, then B is independently substituted with two to three substitutents selected from the group consisting of C1-3alkoxy and hydroxy,
provided that, when B is phenyl substituted at the 3,4-, 3,5- or 4,5-positions with an unbranched C1-3alkoxy substitutent at each position, then phenyl may be further optionally substituted at a remaining open 3-, 4-, or 5-position with an additional C1-3alkoxy or hydroxy substitutent, and
provided that B is other than 3-hydroxy-4-methoxy-phenyl and 3-(n-propyloxy)-4-methoxy-phenyl;
E is hydrogen, halogen, C1-3alkoxy, C2-5alkyl-RE, or —CH═CH—C0-3alkyl-RE;
wherein RE is selected from the group consisting of carboxy, amino, (C1-6alkyl)amino, di(C1-6alkyl)amino, aminocarbonyl, (C1-6alkyl)aminocarbonyl, di(C1-6alkyl)aminocarbonyl, (C1-6alkyl)carbonylamino, C1-6alkoxycarbonylamino, aminocarbonyl(C1-6)alkoxy, ureido, thioureido, aminosulfonyl, C1-6alkylsulfonyl, C1-6alkylsulfonylamino, aminosulfonyloxy, (C1-6alkyl)aminosulfonyloxy, di(C1-6alkyl)aminosulfonyloxy, aminosulfonylamino, (C1-6alkyl)aminosulfonylamino, di(C1-6alkyl)aminosulfonylamino, (R200)(Ra)aminocarbonyl-(Rc)amino, R200carbonylamino, R200oxycarbonyl-(Ra)amino, (R200)(Ra)aminocarbonyloxy, R200oxysulfonyl-(Ra)amino, R200sulfonyl-(Ra)amino, (R200)(Ra)aminosulfonyloxy, and (R200)(Ra)aminosulfonyl-(Rc)amino;
X and Y are independently O or S;
and enantiomers, diastereomers, tautomers, solvates, and pharmaceutically acceptable salts thereof.

34 more elements

Facts

Application

11/651,848Filed 10 Jan 2007

Priority

10 Jan 2006

Published

16 Aug 2007

Term ends

Not estimatedThe source records don’t support an estimate.

Classification36 codes

C07D 209/48
Iso-indoles; Hydrogenated iso-indoles: with oxygen atoms in positions 1 and 3, e.g. phthalimide
A61P 1/12
Drugs for disorders of the alimentary tract or the digestive system: antidiarrhoeals
A61P 1/18
Drugs for disorders of the alimentary tract or the digestive system: for pancreatic disorders, e.g. pancreatic enzymes
A61P 3/10
For glucose homeostasis: for hyperglycaemia, e.g. antidiabetics