US 7,741,356 B2Granted

Compounds as opioid receptor modulators

AssigneeJanssen Pharmaceutica NV

InventorsHenry J. Breslin, Chaozhong Cai, Wei He, Robert W. Kavash

Life of this patent

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Abstract

The present invention is directed to novel opioid receptor modulators of Formula (I). The invention further relates to methods for preparing such compounds, pharmaceutical compositions containing them, and their use in the treatment of disorders that may be ameliorated or treated by the modulation of opioid receptors.

Claims43

Dependent claims

A compound of Formula (I)

wherein:
R1 is selected from the group consisting of hydrogen, C1-6alkyl, cycloalkyl, heterocyclyl, aryl(C1-6)alkyl, and heteroaryl(C1-6)alkyl;
wherein when R1 is phenyl(C1-6)alkyl, phenyl is optionally fused to a heterocyclyl or cycloalkyl;
wherein when R1 is C1-2alkyl, said C1-2alkyl is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkoxy, aryl, cycloalkyl, heterocyclyl, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, and carboxy;
and further, wherein when R1 is C3-6alkyl, said C3-6alkyl is optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkoxy, aryl, cycloalkyl, heterocyclyl, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, and carboxy;
wherein the cycloalkyl and heterocyclyl of C1-2alkyl and C3-6alkyl are optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, carboxy, aryl(C1-6)alkoxycarbonyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, and aminosulfonyl;
furthermore, wherein the cycloalkyl and heterocyclyl of R1 are optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, carboxy, aryl(C1-6)alkoxycarbonyl, C1-6alkoxycarbonyl, aminocarbonyl,
C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, and aminosulfonyl;
furthermore, wherein the aryl and heteroaryl portion of the R1 substituents aryl(C1-6)alkyl and heteroaryl(C1-6)alkyl, are optionally substituted with one to three R11 substituents independently selected from the group consisting of C1-6alkyl;
hydroxy(C1-6)alkyl;
C1-6alkoxy;
C6-10aryl(C1-6)alkyl;
C6-10aryl(C1-6) alkoxy;
C6-10aryl;
heteroaryl optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and carboxy;
cycloalkyl;
heterocyclyl;
C6-10aryloxy;
heteroaryloxy;
cycloalkyloxy;
heterocyclyloxy;
amino;
C1-6alkylamino;
(C1-6alkyl)2amino;
C3-6cycloalkylaminocarbonyl;
hydroxy(C1-6) alkylaminocarbonyl;
C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl;
heterocyclylcarbonyl;
carboxy;
C1-6alkoxycarbonyl;
C1-6alkoxycarbonyloxy;
C1-6alkylcarbonyl;
C1-6alkylcarbonylamino;
aminocarbonyl;
C1-6alkylaminocarbonyl;
(C1-6alkyl)2aminocarbonyl;
cyano;
halogen;
trifluoromethyl;
trifluoromethoxy;
and hydroxy;
provided that no more than one R11 substituent is selected from the group consisting of C6-10aryl(C1-6)alkyl;
C6-10aryl(C1-6)alkoxy;
C6-10aryl;
heteroaryl optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and carboxy;
cycloalkyl;
heterocyclyl;
C6-10aryloxy;
heteroaryloxy;
cycloalkyloxy;
C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl;
heterocyclylcarbonyl, and heterocyclyloxy;
R2 is hydrogen, C1-8alkyl, hydroxy(C1-8)alkyl, C6-10aryl(C1-6)alkoxy(C1-6)alkyl, or C6-10aryl(C1-8)alkyl;
wherein the C6-10aryl group in the C6-10aryl-containing substituents of R2 are optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, hydroxy, amino, C1-6alkylamino, (C1-6alkyl)2amino, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, cyano, fluoro, chloro, bromo, trifluoromethyl, and trifluoromethoxy;
and, wherein the C1-6alkyl and C1-6alkoxy substituents of aryl are optionally substituted with hydroxy, amino, C1-6alkylamino, (C1-6alkyl)2amino, or aryl;
A is a-1, optionally substituted with R3 and R5;
wherein
A-B is N—C;
R3 is one to two substituents independently selected from the group consisting of C1-6alkyl, aryl, aryl(C1-6)alkyl, aryl(C2-6)alkenyl, aryl(C2-6)alkynyl, heteroaryl, heteroaryl(C1-6)alkyl, heteroaryl(C2-6)alkenyl, heteroaryl(C2-6)alkynyl, amino, C1-6alkylamino, (C1-6alkyl)2amino, arylamino, heteroarylamino, aryloxy, heteroaryloxy, trifluoromethyl, and halogen;
wherein the aryl, heteroaryl, and the aryl and heteroaryl of aryl(C1-6)alkyl, aryl(C2-6)alkenyl, aryl(C2-6)alkynyl, heteroaryl(C1-6)alkyl, heteroaryl(C2-6)alkenyl, heteroaryl(C2-6)alkynyl, arylamino, heteroarylamino, aryloxy, and heteroaryloxy, are optionally substituted with one to five fluoro substituents or one to three substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, C6-10aryl(C1-6)alkyl, C6-10aryl(C1-6)alkoxy, C6-10aryl, C6-10aryloxy, heteroaryl(C1-6)alkyl, heteroaryl(C1-6)alkoxy, heteroaryl, heteroaryloxy, C6-10arylamino, heteroarylamino, amino, C1-6alkylamino, (C1-6alkyl)2amino, carboxy(C1-6)alkylamino, carboxy, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, C1-6alkylcarbonylamino, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, carboxy(C1-6)alkylaminocarbonyl, cyano, halogen, trifluoromethyl, trifluoromethoxy, hydroxy, C1-6alkylsulfonyl, and C1-6alkylsulfonylamino;
provided that no more than one such substituent on the aryl or heteroaryl portion of R3 is selected from the group consisting of C6-10aryl(C1-6)alkyl, C6-10aryl(C1-6)alkoxy, C6-10aryl, C6-10aryloxy, heteroaryl(C1-6)alkyl, heteroaryl(C1-6)alkoxy, heteroaryl, heteroaryloxy, C6-10arylamino, heteroarylamino;
and wherein C1-6alkyl and C1-6alkyl of aryl(C1-6)alkyl and heteroaryl(C1-6)alkyl are optionally substituted with a substituent selected from the group consisting of hydroxy, carboxy, C1-4alkoxycarbonyl, amino, C1-6alkylamino, (C1-6alkyl)2amino, aminocarbonyl, (C1-4)alkylaminocarbonyl, di(C1-4)alkylaminocarbonyl, aryl, heteroaryl, arylamino, heteroarylamino, aryloxy, heteroaryloxy, aryl(C1-4)alkoxy, and heteroaryl(C1-4)alkoxy;
R4 is C6-10aryl or a heteroaryl selected from the group consisting of furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolinyl, benzofuryl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolizinyl, quinolinyl, isoquinolinyl and quinazolinyl;
wherein R4 is optionally substituted with one to three R41 substituents independently selected from the group consisting of (C1-6)alkyl optionally substituted with amino, C1-6alkylamino, or (C1-6alkyl)2amino;
(C1-6)alkoxy;
phenyl(C1-6)alkoxy;
phenyl(C1-6)alkylcarbonyloxy wherein C1-6 alkyl is optionally substituted with amino;
a non fused 5-membered-heteroaryl(C1-6)alkylcarbonyloxy;
a non fused 5-membered-heteroaryl;
hydroxy;
halogen;
aminosulfonyl;
formylamino;
aminocarbonyl;
C1-6alkylaminocarbonyl wherein (C1-6)alkyl is optionally substituted with amino, C1-6alkylamino, or (C1-6alkyl)2amino;
(C1-6alkyl)2aminocarbonyl wherein each (C1-6)alkyl is optionally substituted with amino, C1-6alkylamino, or (C1-6alkyl)2amino;
heterocyclylcarbonyl wherein heterocyclyl is a 5-7 membered nitrogen-containing ring and said heterocyclyl is attached to the carbonyl carbon via a nitrogen atom;
carboxy;
or cyano;
and wherein the phenyl portion of phenyl(C1-6)alkylcarbonyloxy is optionally substituted with (C1-6)alkyl (C1-6) alkoxy, halogen, cyano, amino, or hydroxy;
provided that no more than one R41 is C1-6alkyl substituted with C1-6alkylamino or (C1-6alkyl)2amino;
aminosulfonyl;
formylamino;
aminocarbonyl;
C1-6alkylaminocarbonyl;
(C1-6alkyl)2aminocarbonyl;
heterocyclylcarbonyl;
hydroxy;
carboxy;
or a phenyl- or heteroaryl-containing substituent;
R5 is a substituent on a nitrogen atom of ring A selected from the group consisting of hydrogen and C1-4alkyl;
R6 is hydrogen or C1-6alkyl;
R7 is hydrogen or C1-6alkyl;
Ra and Rb are independently selected from the group consisting of hydrogen, C1-6alkyl, and C1-6alkoxycarbonyl;
alternatively, when Ra and Rb are each other than hydrogen, Ra and Rb are optionally taken together with the nitrogen atom to which they are both attached to form a five to eight membered monocyclic ring;
L is O;
and pharmaceutically acceptable enantiomers, diastereomers, racemates, and salts thereof.

94 more elements

A compound of Formula (Ia):

wherein:
R1 is selected from the group consisting of hydrogen, C1-6alkyl, aryl(C1-4)alkyl, and heteroaryl(C1-4)alkyl;
wherein the aryl and heteroaryl portion of aryl(C1-4)alkyl and heteroaryl(C1-4) alkyl are optionally substituted with one to three R11 substituents independently selected from the group consisting of C1-6alkoxy;
heteroaryl optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and carboxy;
carboxy;
C1-4alkoxycarbonyl;
C1-4alkoxycarbonyloxy;
aminocarbonyl;
C1-4alkylaminocarbonyl;
C3-6cycloalkylaminocarbonyl;
hydroxy(C1-6) alkylaminocarbonyl;
C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl;
heterocyclylcarbonyl;
cyano;
halogen;
trifluoromethoxy;
and hydroxy;
provided that no more than one R11 is heteroaryl (optionally substituted with one to two C1-4alkyl substituents);
C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl;
or heterocyclylcarbonyl;
R2 is selected from the group consisting of hydrogen, C1-4alkyl, hydroxy(C1-4) alkyl, and phenyl(C1-6)alkoxy(C1-4)alkyl;
wherein said phenyl is optionally substituted with one to two substituents independently selected from the group consisting of C1-3alkyl, C1-3alkoxy, hydroxy, cyano, fluoro, chloro, bromo, trifluoromethyl, and trifluoromethoxy;
R3 is one to two substituents independently selected from the group consisting of C1-6alkyl, halogen, and aryl;
wherein aryl is optionally substituted with one to three substituents independently selected from the group consisting of halogen, carboxy, aminocarbonyl, C1-3alkylsulfonylamino, cyano, hydroxy, amino, C1-3alkylamino, and (C1-3alkyl)2amino;
R4 is C6-10aryl optionally substituted with one to three R41 substituents independently selected from the group consisting of (C1-3)alkyl, (C1-6) alkoxy, phenyl(C1-6)alkoxy;
hydroxy;
halogen;
formylamino;
aminocarbonyl;
C1-6alkylaminocarbonyl;
(C1-6alkyl)2aminocarbonyl;
heterocyclylcarbonyl wherein heterocyclyl is a 5-7 membered nitrogen-containing ring and said heterocyclyl is attached to the carbonyl carbon via a nitrogen atom;
carboxy;
and cyano;
provided that no more than one R41 substituent is formylamino, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, heterocyclylcarbonyl, hydroxy, carboxy, or a phenyl-containing substituent.
R5 is hydrogen or methyl;
Ra and Rb are independently hydrogen or C1-3alkyl;
or, when Ra and Rb are each other than hydrogen, Ra and Rb are optionally taken together with the nitrogen atom to which they are both attached to form a five to seven membered monocyclic ring;
and pharmaceutically acceptable enantiomers, diastereomers, racemates, and salts thereof.

36 more elements

A compound of Formula (Ia) wherein:

R1 is selected from the group consisting of phenyl(C1-3)alkyl, pyridinyl(C1-3) alkyl, and furanyl(C1-3)alkyl;
wherein phenyl, pyridinyl, and furanyl are optionally substituted with one to three R11 substituents independently selected from the group consisting of is C1-3alkoxy;
tetrazolyl, C3-6cycloalkylaminocarbonyl;
hydroxy(C1-4)alkylaminocarbonyl;
C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl;
morpholin-4-ylcarbonyl;
chloro;
fluoro;
trifluoromethoxy;
methoxycarbonyl;
and carboxy;
provided that no more than one R11 is C6-10arylaminocarbonyl;
R2 is hydrogen or methyl;
R3 is one to two substituents independently selected from the group consisting of methyl and phenyl;
wherein phenyl is optionally substituted with one to three substituents independently selected from the group consisting of chloro and carboxy;
R4 is phenyl substituted at the 4-position with hydroxy, C1-3alkylaminocarbonyl, or aminocarbonyl, and optionally substituted with one to two substituents independently selected from the group consisting of methyl, methoxy, and benzyloxy;
R5 is hydrogen;
Ra and Rb are each hydrogen;
and pharmaceutically acceptable enantiomers, diastereomers, racemates, and salts thereof.

16 more elements

A compound of Formula (Ib)

Formula (Ib)
wherein L is O and R1, R2, R3-1, R3-2, R5, Ra,
Rb, and R41 are dependently selected from the
group consisting of:
R1
R2
R3-1
R3-2
R5
R41
Ra/Rb
2-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
Aminocarbonyl-
aminocarbonyl
phenylmethyl
2-Cyano-phenyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
aminocarbonyl
2-Bromo-phenyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
aminocarbonyl
3-Carboxy-4-
methyl
phenyl
H
H
4-aminocarbonyl
H
methoxy-phenyl
methyl
3-Carboxy-4-
H
phenyl
H
H
4-aminocarbonyl
H
methoxy-phenyl
methyl
3-Carboxy-4-
H
phenyl
H
H
2,6-dimethyl-4-
H
methoxy-phenyl
aminocarbonyl
methyl
3-
H
phenyl
H
H
2,6-dimethyl-4-
H
Methoxycarbonyl-
aminocarbonyl
4-methoxy-
phenylmethyl
3-(1H-tetrazol-5-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
yl)-4-methoxy-
phenylmethyl
3-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
Methoxycarbonyl-
aminocarbonyl
phenylmethyl
3-Methoxy
methyl
naphthalen-
H
H
2,6-dimethyl-4-
H
carbonyl-
1-yl
aminocarbonyl
phenylmethyl
3-Carboxy-
methyl
naphthalen-
H
H
2,6-dimethyl-4-
H
phenylmethyl
1-yl
3-Carboxy-
methyl
4-chloro-
Me
H
2 ,6-dimethyl-4-
H
phenylmethyl
phenyl
4-Carboxy-
methyl
naphthalen-
H
H
2,6-dimethyl-4-
H
phenylmethyl
1-yl
3-Methoxy-4-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
carboxy-
aminocarbonyl
phenylmethyl
3,4-Dihydroxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
Piperidin-4-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
ylmethyl
hydroxy
3-Methoxy
methyl
phenyl
H
H
2,6-dimethyl-4-
H
carbonyl-4-
aminocarbonyl
methoxy-phenyl
methyl
3-Carboxy-4-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methoxy-
aminocarbonyl
phenylmethyl
3,4-Dimethoxy-
methyl
3-bromo
H
H
2,6-dimethyl-4-
H
phenylmethyl
phenyl
aminocarbonyl
3,4-Dimethoxy-
methyl
3-carboxy
H
H
2,6-dimethyl-4-
H
phenylmethyl
phenyl
aminocarbonyl
3,4-Dimethoxy-
benzyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
oxy
hydroxy
methyl
3,4-Dimethoxy-
methyl
3-amino
H
H
2,6-dimethyl-4-
H
phenylmethyl
carbonyl
aminocarbonyl
phenyl
3,4-Dimethoxy-
methyl
3-cyano
H
H
2,6-dimethyl-4-
H
phenylmethyl
phenyl
aminocarbonyl
Isopropyl
H
quinoxalin-
Me
H
2,6-dimethyl-4-
H
8-yl
hydroxy
3,4-Dimethoxy-
methyl
2-bromo
H
H
2,6-dimethyl-4-
H
phenylmethyl
phenyl
aminocarbonyl
3,4-Dimethoxy-
methyl
2-cyano
H
H
2,6-dimethyl-4-
H
phenylmethyl
phenyl
aminocarbonyl
3,4-Dimethoxy-
methyl
2-amino
2,6-dimethyl-4-
H
phenylmethyl
carbonyl
aminocarbonyl
phenyl
3,4-Dimethoxy-
methyl
2-carboxy
H
H
2,6-dimethyl-4-
H
phenylmethyl
phenyl
aminocarbonyl
3,4-Dibenzyloxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
[1,3]benzo
methyl
phenyl
H
H
2,6-dimethyl, 4-
H
dioxal-5-yl
hydroxy
4-Methoxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
3-Methoxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
2,4-Dimethoxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
3,4-Dimethoxy-
H
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
Isopropyl
H
4-methyl
H
H
2,6-dimethyl-4-
H
carbonyl
hydroxy
phenyl
Isopropyl
H
3-fluoro, 4-
Me
H
2,6-dimethyl-4-
H
carboxy-
hydroxy
phenyl
Isopropyl
H
2-phenyl-
Me
H
2,6-dimethyl-4-
H
ethyl
hydroxy
en-1-yl
Isopropyl
H
4-hydroxy
Me
H
2,6-dimethyl-4-
H
methyl
hydroxy
phenyl
Benzhydryl
H
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
4-cyano
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Benzyl
methyl
4-trifluoro
H
H
2,6-dimethyl-4-
H
methyl
aminocarbonyl
phenyl
Isopropyl
H
3-trifluoro
Me
H
2,6-dimethyl-4-
H
methoxy
hydroxy
phenyl
Isopropyl
H
4-trifluoro
Me
H
2,6-dimethyl-4-
H
methoxy
hydroxy
phenyl
Isopropyl
H
3-methane
Me
H
2,6-dimethyl-4-
H
sulfonyl
hydroxy
amino
phenyl
Isopropyl
H
4-(2-
Me
H
2,6-dimethyl-4-
H
carboxy
hydroxy
ethyl)
phenyl
Isopropyl
H
3-amino-5-
Me
H
2,6-dimethyl-4-
H
carboxy
hydroxy
phenyl
3-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
4-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
carboxy
4-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
aminocarbonyl
4-Methoxy
methyl
phenyl
H
H
2,6-dimethyl-4-
H
carbonyl-
aminocarbonyl
phenylmethyl
3-Methoxy
methyl
phenyl
H
H
2,6-dimethyl-4-
H
carbonyl-
hydroxy
phenylmethyl
1-Benzyloxy
methyl
phenyl
H
H
2,6-dimethyl-4-
H
carbonyl-
hydroxy
piperadin-4-
ylmethyl
Furan-2-yl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
Furan-3-yl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
Cyclohexyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
Pyridin-4-yl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
Benzyl
methyl
4-chloro
Me
H
2,6-dimethyl-4-
H
phenyl
aminocarbonyl
Benzyl
methyl
3-fluoro
H
H
2,6-dimethyl-4-
H
phenyl
aminocarbonyl
Isopropyl
H
3-cyano
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
2,5-difluoro
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
4-methane
Me
H
2,6-dimethyl-4-
H
sulfonyl
hydroxy
phenyl
Benzyl
benzyl
phenyl
H
H
2,6-dimethyl-4-
H
oxy
aminocarbonyl
methyl
Isopropyl
H
Br
Me
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
4-dimethyl
Me
H
2,6-dimethyl-4-
H
amino
hydroxy
phenyl
Isopropyl
H
3-dimethyl
Me
H
2,6-dimethyl-4-
H
amino
hydroxy
carbonyl
phenyl
Isopropyl
H
3-hydroxy
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
4-amino
Me
H
2,6-dimethyl-4-
H
carbonyl
hydroxy
phenyl
Isopropyl
H
3-chloro
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
2,4-difluoro
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
3-methane
Me
H
2,6-dimethyl-4-
H
sulfonyl
hydroxy
phenyl
Isopropyl
H
3-amino
Me
H
2,6-dimethyl-4-
H
carbonyl
hydroxy
phenyl
Benzyl
methyl
4-trifluoro
Me
H
2,6-dimethyl-4-
H
methyl
aminocarbonyl
phenyl
3,4-Dimethoxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
aminocarbonyl
Benzyl
methyl
4-fluoro
H
H
2,6-dimethyl-4-
H
phenyl
aminocarbonyl
4-Dimethylamino-
methyl
phenyl
H
Me
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
4-Methylamino-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
4-Methylcarbonyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
amino-phenyl
hydroxy
methyl
4-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
4-Hydroxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
Benzyl
methyl
4-fluoro
H
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
methyl
4-fluoro
H
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
hydroxy
phenyl
H
H
2,6-dimethyl-4-
H
methyl
aminocarbonyl
Isopropyl
H
phenyl
H
H
2,6-dimethyl, 4-
H
aminocarbonyl
3,4-Dichloro-
H
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
4-Methylcarbonyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
oxy-phenyl
hydroxy
methyl
4-Methoxy
methyl
phenyl
H
H
2,6-dimethyl-4-
H
carbonyl-
hydroxy
phenylmethyl
3-Aminocarbonyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
3-Cyano-phenyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
Pyridin-3-yl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
Pyridin-2-yl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
1-(R)-Phenylethyl
H
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
1-(R)-Phenylethyl
H
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
2-Methoxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
2,6-Dichloro-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
3-Phenoxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
Naphthalen-1-yl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
Naphthalen-2-yl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
3-Bromo-phenyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
3,4-Dimethoxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
2,4-Dichloro-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
Benzyl
isobutyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Benzyl
benzyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Benzyl
isopropyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Benzyl
H
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
3-Phenyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
prop-1-yl
aminocarbonyl
2-Phenylethyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
1-Phenylethyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
diastereomer A
aminocarbonyl
1-Phenylethyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
diasteromer B
aminocarbonyl
Benzyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
Isopropyl
H
4-biphenyl
Me
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
3-fluoro
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
2-fluoro
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
hydroxy
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
H
hydroxy
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
Isopropyl
3-(amino
phenyl
H
H
2,6-dimethyl-4-
H
methyl)
hydroxy
phenyl
methyl
Isopropyl
3-amino
phenyl
H
H
2,6-dimethyl-4-
H
carbonyl
hydroxy
phenyl
methyl
Isopropyl
3-cyano
phenyl
H
H
2,6-dimethyl-4-
H
phenyl
hydroxy
methyl
Isopropyl
H
4-carboxy
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
pyridin-3-yl
Me
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
4-methoxy
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
3,5-difluoro
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Cyclohexyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
Carboxymethyl
H
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
3-hydroxy
Me
H
2,6-dimethyl-4-
H
methyl
hydroxy
phenyl
Isopropyl
H
pyrimidin-5-
Me
H
2,6-dimethyl-4-
H
yl
hydroxy
Isopropyl
H
pyrimidin-5-
Me
H
4-hydroxy
H
yl
Isopropyl
H
3-carboxy
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
3-biphenyl
Me
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
2-methoxy
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
benzyl
phenyl
H
H
3-aminocarbonyl
H
Isopropyl
isopropyl
phenyl
H
H
3-aminocarbonyl
H
Isopropyl
benzyl
phenyl
H
H
2,6-dimethyl-4-
H
oxy
hydroxy
methyl
Isopropyl
isobutyl
phenyl
H
H
2,6-dimethyl-4-[2-
H
(2,6-dimethyl-4-
hydroxyphenyl)-1-
amino-
ethylcarbonxyloxy]
phenyl
Isopropyl
isobutyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
3,5-dichloro
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
3-methoxy
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
Isopropyl
H
2-biphenyl
Me
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
thiophen-3-
Me
H
2,6-dimethyl-4-
H
yl
hydroxy
Isopropyl
H
4-chloro
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
3-methyl
Me
H
2,6-dimethyl-4-
H
carbonyl
hydroxy
amino
phenyl
Isopropyl
H
4-trifluoro
Me
H
2,6-dimethyl-4-
H
methyl
hydroxy
phenyl
Isopropyl
H
naphthal
Me
H
2,6-dimethyl-4-
H
en-2-yl
hydroxy
Isopropyl
H
2-trifluoro
Me
H
2,6-dimethyl-4-
H
methyl
hydroxy
phenyl
Isopropyl
H
thiophen-3-yl
Me
H
4-hydroxy
H
Isopropyl
H
pyridin-3-yl
Me
H
4-hydroxy
H
Isopropyl
H
phenyl
Me
H
4-hydroxy
H
Isopropyl
H
2-chloro
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
naphthal
Me
H
2,6-dimethyl-4-
H
en-1-yl
hydroxy
Isopropyl
benzyl
phenyl
H
H
3-cyano
H
Isopropyl
benzyl
phenyl
H
H
4-hydroxy
H
Isopropyl
benzyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
isopropyl
phenyl
H
H
3-cyano
H
Isopropyl
isopropyl
phenyl
H
H
4-hydroxy
H
Isopropyl
isopropyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
4-fluoro
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
3,5-bis-
Me
H
2,6-dimethyl-4-
H
trifluoro
hydroxy
methyl
phenyl
Isopropyl
H
2-methyl
Me
H
2,6-dimethyl-4-
H
phenyl
hydroxy
Isopropyl
H
phenyl
Me
H
2,6-dimethyl-4-
H
hydroxy
2-Dimethylamino-
H
phenyl
H
H
2,6-dimethyl-4-
H
1-methyl-eth-1-yl
hydroxy
Methyl
isobutyl
phenyl
H
H
3-aminocarbonyl
H
Methyl
isobutyl
phenyl
H
H
3-cyano
H
Ethyl
isopropyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Methyl
isopropyl
phenyl
H
H
4-hydroxy
H
H
3-amino
phenyl
H
H
2,6-dimethyl-4-
H
carbonyl
hydroxy
phenyl
methyl
H
3-cyano
phenyl
H
H
2,6-dimethyl-4-
H
phenyl
hydroxy
methyl
Methyl
isobutyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
H
benzyl
phenyl
H
H
2,6-dimethyl-4-
H
oxy
hydroxy
methyl
H
isobutyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
H
benzyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
Methyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
morpholin-1-
ylcarbonyl
Methyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
ethylamino
carbonyl
Methyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methylamino
carbonyl
H
isopropyl
phenyl
H
H
3-aminocarbonyl
H
H
isopropyl
phenyl
H
H
3-cyano
H
H
isopropyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
H
isopropyl
phenyl
H
H
4-hydroxy
H
Methyl
methyl
phenyl
H
H
4-aminosulfonyl
H
Cyclohexyl
H
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Cyclohexyl
H
phenyl
H
H
2,6-dimethyl-4-
H
4-hydroxy
Cyclopropyl
H
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
Cyclopropyl
H
phenyl
H
H
4-hydroxy
H
methyl
Isopropyl
H
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
H
phenyl
H
H
4-hydroxy
H
Methyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
Ethyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
Methyl
H
phenyl
H
H
4-hydroxy
H
Methyl
H
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Methyl
methyl
phenyl
H
H
4-aminocarbonyl
H
Methyl
methyl
benzyl
H
H
4-hydroxy
H
Methyl
methyl
benzyl
H
H
2,6-dimethyl-4-
H
hydroxy
Methyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
H
methyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Methyl
methyl
phenyl
H
H
4-hydroxy
H
H
methyl
phenyl
H
H
4-hydroxy
H
Ethyl
methyl
phenyl
H
H
4-hydroxy
H
Ethyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Benzyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Benzyl
methyl
phenyl
H
H
4-hydroxy
H
Isopropyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
hydroxy
Isopropyl
methyl
phenyl
H
H
4-hydroxy
H
2-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenyl
aminocarbonyl
methyl
3-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenyl
aminocarbonyl
methyl
2-Bromo-4,5-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
dimethoxy-
aminocarbonyl
phenylmethyl
2-Carboxy-4,5-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
dimethoxy-
aminocarbonyl
phenylmethyl
3-Carboxy-4-
methyl
phenyl
H
H
H
H
methoxy-phenyl
methyl
3-Carboxy-4-
methyl
phenyl
H
H
2,6-dimethyl
H
methoxy-phenyl
methyl
3-Methoxycarbonyl-
methyl
phenyl
H
H
2,6-dimethyl
H
4-methoxy-
phenylmethyl
3,4-Dimethoxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
imidazol-2-yl
3,4-Dimethoxy-
methyl
phenyl
H
H
2,6-dimethyl
H
phenylmethyl
3-Carboxy-4-
methyl
4-chloro
H
H
2,6-dimethyl-4-
H
methoxy-phenyl
aminocarbonyl
methyl
3-Carboxy-4-
methyl
4-chloro
H
H
2,6-dimethyl-4-
H
methoxy-phenyl
aminocarbonyl
methyl
3-Carboxy-4-
methyl
4-chloro
H
H
2,6-dimethyl-4-
H
methoxy-phenyl
aminocarbonyl
methyl
4-Carboxy-
methyl
4-chloro
Me
H
2,6-dimethyl-4-
H
phenylmethyl
phenyl
aminocarbonyl
3-Carboxy-4-
methyl
4-chloro
Cl
H
2,6-dimethyl-4-
H
methoxy-phenyl
phenyl
aminocarbonyl
methyl
3-(1H-tetrazol-5-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
yl)-phenylmethyl
aminocarbonyl
3-Carboxy-4-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
trifluoromethoxy-
aminocarbonyl
phenylmethyl
Bis-3,4-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
trifluoromethoxy-
aminocarbonyl
phenylmethyl
3-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
aminocarbonyl
Quinolin-4-yl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
4-Methoxy
methyl
phenyl
H
H
2,6-dimethyl-4-
H
naphthalen-1-
hydroxy
ylmethyl
4-Trifluoromethoxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
4-Trifluoromethyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
4-Isopropyloxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
hydroxy
3-Ethoxyphenyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methyl
hydroxy
5-Methoxycarbonyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
pyridin-2-yl
aminocarbonyl
methyl
5-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
pyridin-2-
aminocarbonyl
ylmethyl
6-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
pyridin-3-
aminocarbonyl
ylmethyl
6-Methoxycarbonyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
pyridin-3-
aminocarbonyl
ylmethyl
5-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
furan-2-ylmethyl
aminocarbonyl
5-Methoxy
methyl
phenyl
H
H
2,6-dimethyl-4-
H
carbonyl-
aminocarbonyl
furan-2-ylmethyl
3,4-Dimethoxy-
hydroxy
phenyl
H
H
2,6-dimethyl-4-
H
phenylmethyl
methyl
aminocarbonyl
Benzyl
hydroxy
phenyl
H
H
2,6-dimethyl-4-
H
methyl
aminocarbonyl
3-Carboxy-4-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
methoxy-phenyl
hydroxy
methyl
3-Carboxy-4-
methyl
phenyl
H
H
4-hydroxy
H
methoxy-phenyl
methyl
3-Carboxy-4-
methyl
phenyl
H
H
4-hydroxy
H/Me
methoxy-phenyl
methyl
3-Carboxy-4-
H
phenyl
H
H
4-hydroxy
H
methoxy-phenyl
methyl
3-Carboxy-4-
H
phenyl
H
H
4-hydroxy
H/Me
methoxy-phenyl
methyl
3-Carboxy-4-
H
phenyl
H
H
2,6-dimethyl-4-
H
methoxy-phenyl
hydroxy
methyl
3-Methoxycarbonyl-
methyl
phenyl
H
H
H
H
4-methoxy-
phenylmethyl
3-(1H-tetrazol-5-
methyl
phenyl
H
H
4-aminocarbonyl
H
yl)-phenylmethyl
3-Methoxycarbonyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
4-methoxy-
hydroxy
phenylmethyl
3-Methoxycarbonyl
methyl
phenyl
H
H
4-aminocarbonyl
H
3-Carboxy
methyl
phenyl
H
H
4-aminocarbonyl
H
3-Methoxycarbonyl
H
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
3-Carboxy
H
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl
3-Carboxy-4-
methyl
phenyl
H
H
4-benzyloxy-
H/Me
methoxy-
phenylmethyl
3-Carboxy-4-
methyl
phenyl
H
H
4-aminocarbonyl
H
methoxy-
phenylmethyl
3-Carboxy-
methyl
4-chloro
Me
H
4-aminocarbonyl
H
phenyl
3-Methoxycarbonyl-
methyl
phenyl
H
H
4-hydroxy
H
4-methoxy-
phenylmethyl
5-Methoxycarbonyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
furan-2-ylmethyl
hydroxy
5-Carboxy-furan-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
2-ylmethyl
hydroxy
3-Carboxy-4-
methyl
3-bromo
H
H
2,6-dimethyl-4-
H
methoxy-
phenyl
aminocarbonyl
phenylmethyl
3-Carboxy-4-
methyl
4-iodo
H
H
2,6-dimethyl-4-
H
methoxy-
aminocarbonyl
phenylmethyl
3-Carboxy-4-
methyl
2-bromo
H
H
2,6-dimethyl-4-
H
methoxy-
phenyl
aminocarbonyl
phenylmethyl
3-Carboxy-4-
methyl
4-bromo
H
H
2,6-dimethyl-4-
H
methoxy-
aminocarbonyl
phenylmethyl
3-Carboxy-4-
methyl
phenyl
H
H
2,6-dimethyl
H
methoxy-
phenylmethyl
3-Carboxy-4-
methyl
4-chloro
methyl
H
4-hydroxy
H
methoxy-
phenylmethyl
3-Aminocarbonyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
4-methoxy
aminocarbonyl
phenylmethyl
3-(Morpholin-4-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
ylcarbonyl)-4-
aminocarbonyl
methoxy
phenylmethyl
-3-Aminocarbonyl-
methyl
phenyl
H
H
4-hydroxy
H
4-methoxy-
phenylmethyl
3-(Morpholin-4-
methyl
phenyl
H
H
4-hydroxy
H
ylcarbonyl)-4-
methoxy-
phenylmethyl
3-(2-Hydroxy
methyl
phenyl
H
H
2,6-dimethyl-4-
H
eth-1-yl-
aminocarbonyl
aminocarbonyl)-
4-methoxy
phenylmethyl
3-(Cyclopropyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl)-
aminocarbonyl
4-methoxy-
phenylmethyl
3-(Phenylamino
methyl
phenyl
H
H
2,6-dimethyl-4-
H
carbonyl)-4-
aminocarbonyl
methoxy-
phenylmethyl
5-Methoxycarbonyl-
methyl
phenyl
H
H
4-aminocarbonyl
H
furan-2-ylmethyl
5-Carboxy-furan-
methyl
phenyl
H
H
4-aminocarbonyl
H
2-ylmethyl
3-(Phenylamino
methyl
phenyl
H
H
2,6-dimethyl-4-
H
carbonyl)-4-
hydroxy
methoxy-
phenylmethyl
3-(3-carboxyphenyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl)-
hydroxy
4-methoxy-
phenylmethyl
3-(1H-Tetrazol-5-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
yl)-4-methoxy-
hydroxy
phenylmethyl
3-(4-Carboxyphenyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
aminocarbonyl)-
hydroxy
4-methoxy-
phenylmethyl
3-(2-t-Butyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
tetrazol-5-yl)-4-
aminocarbonyl
methoxy-
phenylmethyl
3-Methoxycarbonyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
Methoxy-
4-methoxy-
aminocarbonyl
carbonyl
phenylmethyl
2-Methoxycarbonyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
pyridin-4-yl
aminocarbonyl
methyl
4-Methoxycarbonyl
methyl
phenyl
H
H
2,6-dimethyl-4-
H
pyridin-2-yl
aminocarbonyl
methyl
6-Methoxycarbonyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
pyridin-2-
aminocarbonyl
ylmethyl
3-Methoxycarbonyl-
methyl
phenyl
H
H
2,6-dimethyl-4-
Methoxy-
4-methoxy-
aminocarbonyl
carbonyl
phenylmethyl
2-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H
pyridin-4-
aminocarbonyl
ylmethyl
and
6-Carboxy-
methyl
phenyl
H
H
2,6-dimethyl-4-
H.
pyridin-2-
aminocarbonyl
ylmethyl

2,552 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/079,647Filed 14 Mar 2005 · us provisional application
Priority: 15 Mar 2004
Published: US 2005/0203143 A115 Sep 2005
Granted: 22 Jun 2010
Term ends: Not estimatedThe source records don’t support an estimate.

Classification18 codes

A61K 31/4164
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: 1,3-Diazoles
A61K 9/20
Medicinal preparations characterised by special physical form: pills, tablets, discs, rods
A61K 9/2806
Dragees; Coated pills or tablets , e.g. with film or compression coating: coating materials
A61K 31/4174
1,3-Diazoles: arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole

Family

Application60/553,342Us provisional application · filed 15 Mar 2004
US 2005/0203143 A1Pre-grant publication · published 15 Sep 2005
US 7,741,356 B2This patent

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

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Abstract

A compound of Formula (I)

wherein:
R1 is selected from the group consisting of hydrogen, C1-6alkyl, cycloalkyl, heterocyclyl, aryl(C1-6)alkyl, and heteroaryl(C1-6)alkyl;
wherein when R1 is phenyl(C1-6)alkyl, phenyl is optionally fused to a heterocyclyl or cycloalkyl;
wherein when R1 is C1-2alkyl, said C1-2alkyl is optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkoxy, aryl, cycloalkyl, heterocyclyl, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, and carboxy;
and further, wherein when R1 is C3-6alkyl, said C3-6alkyl is optionally substituted with one to three substituents independently selected from the group consisting of C1-6alkoxy, aryl, cycloalkyl, heterocyclyl, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, and carboxy;
wherein the cycloalkyl and heterocyclyl of C1-2alkyl and C3-6alkyl are optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, carboxy, aryl(C1-6)alkoxycarbonyl, C1-6alkoxycarbonyl, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, and aminosulfonyl;
furthermore, wherein the cycloalkyl and heterocyclyl of R1 are optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, hydroxy, cyano, amino, C1-6alkylamino, (C1-6alkyl)2amino, trifluoromethyl, carboxy, aryl(C1-6)alkoxycarbonyl, C1-6alkoxycarbonyl, aminocarbonyl,
C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, and aminosulfonyl;
furthermore, wherein the aryl and heteroaryl portion of the R1 substituents aryl(C1-6)alkyl and heteroaryl(C1-6)alkyl, are optionally substituted with one to three R11 substituents independently selected from the group consisting of C1-6alkyl;
hydroxy(C1-6)alkyl;
C1-6alkoxy;
C6-10aryl(C1-6)alkyl;
C6-10aryl(C1-6) alkoxy;
C6-10aryl;
heteroaryl optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and carboxy;
cycloalkyl;
heterocyclyl;
C6-10aryloxy;
heteroaryloxy;
cycloalkyloxy;
heterocyclyloxy;
amino;
C1-6alkylamino;
(C1-6alkyl)2amino;
C3-6cycloalkylaminocarbonyl;
hydroxy(C1-6) alkylaminocarbonyl;
C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl;
heterocyclylcarbonyl;
carboxy;
C1-6alkoxycarbonyl;
C1-6alkoxycarbonyloxy;
C1-6alkylcarbonyl;
C1-6alkylcarbonylamino;
aminocarbonyl;
C1-6alkylaminocarbonyl;
(C1-6alkyl)2aminocarbonyl;
cyano;
halogen;
trifluoromethyl;
trifluoromethoxy;
and hydroxy;
provided that no more than one R11 substituent is selected from the group consisting of C6-10aryl(C1-6)alkyl;
C6-10aryl(C1-6)alkoxy;
C6-10aryl;
heteroaryl optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and carboxy;
cycloalkyl;
heterocyclyl;
C6-10aryloxy;
heteroaryloxy;
cycloalkyloxy;
C6-10arylaminocarbonyl wherein C6-10aryl is optionally substituted with carboxy or C1-4alkoxycarbonyl;
heterocyclylcarbonyl, and heterocyclyloxy;
R2 is hydrogen, C1-8alkyl, hydroxy(C1-8)alkyl, C6-10aryl(C1-6)alkoxy(C1-6)alkyl, or C6-10aryl(C1-8)alkyl;
wherein the C6-10aryl group in the C6-10aryl-containing substituents of R2 are optionally substituted with one to two substituents independently selected from the group consisting of C1-6alkyl, C1-6alkoxy, hydroxy, amino, C1-6alkylamino, (C1-6alkyl)2amino, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, cyano, fluoro, chloro, bromo, trifluoromethyl, and trifluoromethoxy;
and, wherein the C1-6alkyl and C1-6alkoxy substituents of aryl are optionally substituted with hydroxy, amino, C1-6alkylamino, (C1-6alkyl)2amino, or aryl;
A is a-1, optionally substituted with R3 and R5;
wherein
A-B is N—C;
R3 is one to two substituents independently selected from the group consisting of C1-6alkyl, aryl, aryl(C1-6)alkyl, aryl(C2-6)alkenyl, aryl(C2-6)alkynyl, heteroaryl, heteroaryl(C1-6)alkyl, heteroaryl(C2-6)alkenyl, heteroaryl(C2-6)alkynyl, amino, C1-6alkylamino, (C1-6alkyl)2amino, arylamino, heteroarylamino, aryloxy, heteroaryloxy, trifluoromethyl, and halogen;
wherein the aryl, heteroaryl, and the aryl and heteroaryl of aryl(C1-6)alkyl, aryl(C2-6)alkenyl, aryl(C2-6)alkynyl, heteroaryl(C1-6)alkyl, heteroaryl(C2-6)alkenyl, heteroaryl(C2-6)alkynyl, arylamino, heteroarylamino, aryloxy, and heteroaryloxy, are optionally substituted with one to five fluoro substituents or one to three substituents independently selected from the group consisting of C1-6alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy, C6-10aryl(C1-6)alkyl, C6-10aryl(C1-6)alkoxy, C6-10aryl, C6-10aryloxy, heteroaryl(C1-6)alkyl, heteroaryl(C1-6)alkoxy, heteroaryl, heteroaryloxy, C6-10arylamino, heteroarylamino, amino, C1-6alkylamino, (C1-6alkyl)2amino, carboxy(C1-6)alkylamino, carboxy, C1-6alkylcarbonyl, C1-6alkoxycarbonyl, C1-6alkylcarbonylamino, aminocarbonyl, C1-6alkylaminocarbonyl, (C1-6alkyl)2aminocarbonyl, carboxy(C1-6)alkylaminocarbonyl, cyano, halogen, trifluoromethyl, trifluoromethoxy, hydroxy, C1-6alkylsulfonyl, and C1-6alkylsulfonylamino;
provided that no more than one such substituent on the aryl or heteroaryl portion of R3 is selected from the group consisting of C6-10aryl(C1-6)alkyl, C6-10aryl(C1-6)alkoxy, C6-10aryl, C6-10aryloxy, heteroaryl(C1-6)alkyl, heteroaryl(C1-6)alkoxy, heteroaryl, heteroaryloxy, C6-10arylamino, heteroarylamino;
and wherein C1-6alkyl and C1-6alkyl of aryl(C1-6)alkyl and heteroaryl(C1-6)alkyl are optionally substituted with a substituent selected from the group consisting of hydroxy, carboxy, C1-4alkoxycarbonyl, amino, C1-6alkylamino, (C1-6alkyl)2amino, aminocarbonyl, (C1-4)alkylaminocarbonyl, di(C1-4)alkylaminocarbonyl, aryl, heteroaryl, arylamino, heteroarylamino, aryloxy, heteroaryloxy, aryl(C1-4)alkoxy, and heteroaryl(C1-4)alkoxy;
R4 is C6-10aryl or a heteroaryl selected from the group consisting of furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, pyrazinyl, indolyl, isoindolyl, indolinyl, benzofuryl, benzothienyl, benzimidazolyl, benzthiazolyl, benzoxazolyl, quinolizinyl, quinolinyl, isoquinolinyl and quinazolinyl;
wherein R4 is optionally substituted with one to three R41 substituents independently selected from the group consisting of (C1-6)alkyl optionally substituted with amino, C1-6alkylamino, or (C1-6alkyl)2amino;
(C1-6)alkoxy;
phenyl(C1-6)alkoxy;
phenyl(C1-6)alkylcarbonyloxy wherein C1-6 alkyl is optionally substituted with amino;
a non fused 5-membered-heteroaryl(C1-6)alkylcarbonyloxy;
a non fused 5-membered-heteroaryl;
hydroxy;
halogen;
aminosulfonyl;
formylamino;
aminocarbonyl;
C1-6alkylaminocarbonyl wherein (C1-6)alkyl is optionally substituted with amino, C1-6alkylamino, or (C1-6alkyl)2amino;
(C1-6alkyl)2aminocarbonyl wherein each (C1-6)alkyl is optionally substituted with amino, C1-6alkylamino, or (C1-6alkyl)2amino;
heterocyclylcarbonyl wherein heterocyclyl is a 5-7 membered nitrogen-containing ring and said heterocyclyl is attached to the carbonyl carbon via a nitrogen atom;
carboxy;
or cyano;
and wherein the phenyl portion of phenyl(C1-6)alkylcarbonyloxy is optionally substituted with (C1-6)alkyl (C1-6) alkoxy, halogen, cyano, amino, or hydroxy;
provided that no more than one R41 is C1-6alkyl substituted with C1-6alkylamino or (C1-6alkyl)2amino;
aminosulfonyl;
formylamino;
aminocarbonyl;
C1-6alkylaminocarbonyl;
(C1-6alkyl)2aminocarbonyl;
heterocyclylcarbonyl;
hydroxy;
carboxy;
or a phenyl- or heteroaryl-containing substituent;
R5 is a substituent on a nitrogen atom of ring A selected from the group consisting of hydrogen and C1-4alkyl;
R6 is hydrogen or C1-6alkyl;
R7 is hydrogen or C1-6alkyl;
Ra and Rb are independently selected from the group consisting of hydrogen, C1-6alkyl, and C1-6alkoxycarbonyl;
alternatively, when Ra and Rb are each other than hydrogen, Ra and Rb are optionally taken together with the nitrogen atom to which they are both attached to form a five to eight membered monocyclic ring;
L is O;
and pharmaceutically acceptable enantiomers, diastereomers, racemates, and salts thereof.

94 more elements

Facts

Application

11/079,647Filed 14 Mar 2005 · us provisional application

Priority

15 Mar 2004

Published

US 2005/0203143 A115 Sep 2005

Granted

22 Jun 2010

Term ends

Not estimatedThe source records don’t support an estimate.

Classification18 codes

A61K 31/4164
Having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole: 1,3-Diazoles
A61K 9/20
Medicinal preparations characterised by special physical form: pills, tablets, discs, rods
A61K 9/2806
Dragees; Coated pills or tablets , e.g. with film or compression coating: coating materials
A61K 31/4174
1,3-Diazoles: arylalkylimidazoles, e.g. oxymetazolin, naphazoline, miconazole