US2008132521A1PendingUtilityA1
Isoquinolinone Derivatives and Their Use As Therapeutic Agents
Est. expiryDec 20, 2022(expired)· nominal 20-yr term from priority
C07D 409/04C07D 405/04C07D 217/24A61P 3/06A61P 9/00A61P 9/10
60
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Claims
Abstract
Compounds of formula (I): wherein n, R 1 , R 2 , R 3 and R 7 are disclosed herein, are useful in treating disease-states associated with nuclear receptor activity. Pharmaceutical compositions comprising and methods of using said compounds are also disclosed herein.
Claims
exact text as granted — not AI-modified1 . A compound of formula (I):
wherein:
n is 0 to 4;
each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
R 2 is alkynyl optionally substituted with —Si(R 4 ) 3 , hydroxyalkyl, optionally substituted aryl, or optionally substituted cycloalkyl,
or R 2 is aryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 2 is heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
R 3 is alkyl or cycloalkylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 3 is aralkyl wherein the aryl group of the aralkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 3 is heteroarylalkyl wherein the heteroaryl group of the heteroarylalkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl;
each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl;
each R 6 is a direct bond or a straight or branched alkylene chain; and
R 7 is hydrogen or aralkyl;
as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers; or as a solvate or polymorph; or as a pharmaceutically acceptable salt thereof;
with the following provisos:
(a) when n is 0, R 7 is hydrogen and R 3 is either benzyl or 4-methylbenzyl, R 2 can not be 4-chlorophenyl, 4-methoxyphenyl, or 3-chlorophenyl;
(b) when R 7 is hydrogen, n is 0 or 1, R 1 is chloro, methyl, trifluoromethyl or methoxy, and R 3 is methyl, R 2 can not be unsubstituted furanyl or thiophenyl optionally substituted by methyl;
(c) when R 7 is hydrogen, n is 0, 1 or 2, each R 1 is independently halo, trifluoromethyl, an alkyl group of 1 to 3 carbons or —R 6 —OR 4 where R 6 is a direct bond and
R 4 is an alkyl group of 1 to 3 carbons, and R 3 is an alkyl group of 1 to 3 carbons, R 2 can not be phenyl optionally substituted by halo, an alkyl group of 1 to 3 carbons or —R 6 —OR 4 where R 6 is a direct bond and R 4 is an alkyl group of 1 to 4 carbons;
(d) when R 7 is hydrogen, n is 0 or 1, R 1 is halo, methyl or methoxy, and R 3 is methyl, R 2 can not be oxazole.
2 . The compound of claim 1 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 2 is alkynyl optionally substituted with —Si(R 4 ) 3 , hydroxyalkyl, optionally substituted aryl, or optionally substituted cycloalkyl, R 3 is alkyl or cycloalkylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); or R 3 is aralkyl wherein the aryl group of the aralkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); or R 3 is heteroarylalkyl wherein the heteroaryl group of the heteroarylalkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen or aralkyl.
3 . The compound of claim 2 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, halo, haloalkyl or hydroxy; R 2 is alkynyl optionally substituted with —Si(R 4 ) 3 , hydroxyalkyl, optionally substituted aryl, or optionally substituted cycloalkyl, R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; R 5 is selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen.
4 . The compound of claim 3 wherein:
n is 0; R 2 is ethynyl optionally substituted with —Si(R 4 ) 3 , hydroxyalkyl, phenyl or cyclohexyl optionally substituted by hydroxy, R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl and aryl; and each R 4 is independently selected from the group consisting of hydrogen, methyl, phenyl and benzyl.
5 . The compound of claim 4 selected from the group consisting of the following:
2-biphenyl-4-ylmethyl-3-trimethylsilanylethynyl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(3-hydroxy-3-methylbut-1-ynyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-trimethylsilanylethynyl-2H-isoquinolin-1-one;
2-benzyl-3-(3-hydroxy-3-methylbut-1-ynyl)-2H-isoquinolin-1-one;
3-(3-hydroxy-3-methylbut-1-ynyl)-2-(4-methylbenzyl)-2H-isoquinolin-1-one;
2-benzyl-3-trimethylsilanylethynyl-2H-isoquinolin-1-one;
2-(4-methylbenzyl)-3-trimethylsilanylethynyl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-phenylethynyl-2H-isoquinolin-1-one; and
2-(2,4-dimethylbenzyl)-3-(1-hydroxycyclohexylethynyl)-2H-isoquinolin-1-one.
6 . The compound of claim 1 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 2 is heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 3 is alkyl or cycloalkylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); or R 3 is aralkyl wherein the aryl group of the aralkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); or R 3 is heteroarylalkyl wherein the heteroaryl group of the heteroarylalkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen or aralkyl.
7 . The compound of claim 6 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 2 is heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 3 is aralkyl wherein the aryl group of the aralkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen or aralkyl.
8 . The compound of claim 7 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 2 is heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, aryl, cyano, nitro, halo, haloalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; R 5 is selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen.
9 . The compound of claim 8 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, halo, haloalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 2 is thiophenyl, benzothiophenyl, furanyl or benzofuranyl, each optionally substituted with one or more substituents selected from the group consisting of alkyl, cyano, nitro, halo, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, aryl, cyano, nitro, halo, haloalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen.
10 . The compound of claim 9 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, halo, haloalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 2 is thiophenyl, benzothiophenyl, furanyl or benzofuranyl, each of which are optionally substituted with one or more substituents independently selected from the group consisting of halo, —R 6 —OR 4 , optionally substituted phenyl and optionally substituted pyridinyl; R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, aryl, cyano, nitro, halo, haloalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; each R 4 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen.
11 . The compound of claim 10 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, halo, haloalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 2 is thiophenyl, benzothiophenyl, furanyl or benzofuranyl, each of which are optionally substituted with one or more substituents independently selected from the group consisting of halo and —R 6 —OR 4 ; R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, aryl, cyano, nitro, halo, haloalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; each R 4 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen.
12 . The compound of claim 11 selected from the group consisting of the following:
2-benzyl-3-thiophen-2-yl-2H-isoquinolin-1-one;
2-benzyl-3-furan-3-yl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-thiophen-3-yl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-furan-2-yl-2H-isoquinolin-1-one;
2-benzyl-3-thiophen-3-yl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-thiophen-2-yl-2H-isoquinolin-1-one;
3-benzo[b]thiophen-2-yl-2-(4-methylbenzyl)-2H-isoquinolin-1-one;
3-benzofuran-2-yl-2-(4-methylbenzyl)-2H-isoquinolin-1-one;
3-benzofuran-2-yl-2-(2,4-dimethylbenzyl)-2H-isoquinolin-1-one;
3-benzo[b]thiophen-2-yl-2-(2,4-dimethylbenzyl)-2H-isoquinolin-1-one; and
3-(5-bromothiophen-2-yl)-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one.
13 . The compound of claim 10 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, halo, haloalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 2 is thiophenyl or furanyl, each of which is substituted with phenyl or pyridinyl, where the phenyl and the pyridinyl are each optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 to 2); R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, aryl, cyano, nitro, halo, haloalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; each R 4 is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen.
14 . The compound of claim 13 selected from the group consisting of the following:
8-chloro-2-(2,4-difluorobenzyl)-3-[5-(3,4-dimethoxyphenyl)thiophen-2-yl]-2H-isoquinolin-1-one;
3-[5-(3,5-bis-trifluoromethylphenyl)thiophen-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[5-(4-methanesulfonylphenyl)thiophen-2-yl]-2H-isoquinolin-1-one;
8-chloro-3-[5-(3-chloro-4-ethoxyphenyl)thiophen-2-yl]-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-3-[5-(3-chloro-4-ethoxyphenyl)furan-2-yl]-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
3-[5-(3,5-bis-trifluoromethylphenyl)furan-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[5-(4-methanesulfonylphenyl)furan-2-yl]-2H-isoquinolin-1-one;
8-chloro-3-[4-(3-chloro-4-ethoxyphenyl)thiophen-2-yl]-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
3-[4-(3,5-bis-trifluoromethylphenyl)thiophen-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[4-(4-methanesulfonylphenyl)thiophen-2-yl]-2H-isoquinolin-1-one;
3-[4-(4-amino-3-trifluoromethylphenyl)thiophen-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
3-[4-(4-amino-3-chloro-phenyl)thiophen-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[4-(4-ethoxy-3-trifluoromethylphenyl)thiophen-2-yl]-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[5-(4-ethoxy-3-trifluoromethylphenyl)thiophen-2-yl]-2H-isoquinolin-1-one;
3-[5-(4-amino-3-trifluoromethylphenyl)thiophen-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
3-[5-(4-amino-3-chloro-phenyl)thiophen-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-3-[4-(3-chloro-4-diethylamino-phenyl)thiophen-2-yl]-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-3-[4-(3-chloro-4-ethylamino-phenyl)thiophen-2-yl]-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-3-[4-(3-chloro-4-ethoxyphenyl)furan-2-yl]-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
3-[4-(3,5-bis-trifluoromethylphenyl)furan-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[5-(4-ethylamino-3-trifluoromethylphenyl)thiophen-2-yl]-2H-isoquinolin-1-one;
8-chloro-3-[5-(3-trifluoromethyl-4-(bis-methanesulfonylamino)-phenyl)thiophen-2-yl]-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[4-(4-methanesulfonylphenyl)furan-2-yl]-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[5-(3-ethanesulfonyl-5-trifluoromethylphenyl)thiophen-2-yl]-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[4-(3-ethanesulfonyl-5-trifluoromethylphenyl)furan-2-yl]-2H-isoquinolin-1-one;
3-[4-(4-amino-3-trifluoromethylphenyl)furan-2-yl]-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[5-(3-ethylsulfanyl-5-trifluoromethylphenyl)furan-2-yl]-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[5-(3-ethanesulfonyl-5-trifluoromethylphenyl)furan-2-yl]-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[4-(4-ethylamino-3-trifluoromethylphenyl)furan-2-yl]-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[5-(6-ethoxy-pyridin-3-yl)-thiophen-2-yl]-2H-isoquinolin-1-one; and
5-{5-[8-chloro-2-(2,4-difluorobenzyl)-1-oxo-1,2-dihydro-isoquinolin-3-yl]-thiophen-2-yl}-2-ethoxy-nicotinonitrile.
15 . The compound of claim 1 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 2 is aryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 3 is alkyl or cycloalkylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); or R 3 is aralkyl wherein the aryl group of the aralkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); or R 3 is heteroarylalkyl wherein the heteroaryl group of the heteroarylalkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen or aralkyl.
16 . The compound of claim 15 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 2 is aryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 3 is aralkyl wherein the aryl group of the aralkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen or aralkyl.
17 . The compound of claim 16 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, halo, haloalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 2 is phenyl optionally substituted with one or more substituents selected from the group consisting of alkyl, cyano, nitro, halo, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , and —R 6 —N(R 4 )C(O)R 4 ; R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, aryl, cyano, nitro, halo, haloalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen.
18 . The compound of claim 17 wherein:
n is 0 or 1; R 1 is alkyl or halo; R 2 is phenyl optionally substituted with one or more substituents selected from the group consisting of alkyl, optionally substituted aryl and optionally substituted aralkyl; and R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, halo and aryl.
19 . The compound of claim 18 selected from the group consisting of the following:
2-biphenyl-4-ylmethyl-3-m-tolyl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-m-tolyl-2H-isoquinolin-1-one;
2-benzyl-3-m-tolyl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(3,5-dimethylphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-phenyl-2H-isoquinolin-1-one;
5-chloro-2-(2,4-dimethylbenzyl)-3-m-tolyl-2H-isoquinolin-1-one;
5-chloro-2-(4-methylbenzyl)-3-m-tolyl-2H-isoquinolin-1-one;
5-chloro-2-(2,4-dimethylbenzyl)-3-phenyl-2H-isoquinolin-1-one;
5-chloro-2-(4-methylbenzyl)-3-phenyl-2H-isoquinolin-1-one;
8-chloro-2-(2,4-dimethylbenzyl)-3-phenyl-2H-isoquinolin-1-one;
8-chloro-2-(2,4-dimethylbenzyl)-3-m-tolyl-2H-isoquinolin-1-one;
2-benzyl-8-chloro-3-m-tolyl-2H-isoquinolin-1-one;
2-benzyl-8-chloro-3-phenyl-2H-isoquinolin-1-one;
2-benzyl-8-methyl-3-m-tolyl-2H-isoquinolin-1-one;
8-methyl-2-(4-methylbenzyl)-3-m-tolyl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-8-methyl-3-m-tolyl-2H-isoquinolin-1-one;
2-benzyl-8-methyl-3-phenyl-2H-isoquinolin-1-one;
8-methyl-2-(4-methylbenzyl)-3-phenyl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-8-methyl-3-phenyl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-7-methyl-3-phenyl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-7-methyl-3-m-tolyl-2H-isoquinolin-1-one;
7-methyl-2-(4-methylbenzyl)-3-phenyl-2H-isoquinolin-1-one;
7-methyl-2-(4-methylbenzyl)-3-m-tolyl-2H-isoquinolin-1-one; and
7-chloro-2-(2,4-dimethylbenzyl)-3-m-tolyl-2H-isoquinolin-1-one.
2-benzyl-7-methyl-3-m-tolyl-2H-isoquinolin-1-one;
2-benzyl-7-methyl-3-phenyl-2H-isoquinolin-1-one;
2-benzyl-6-methyl-3-m-tolyl-2H-isoquinolin-1-one;
2-benzyl-6-methyl-3-phenyl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-6-methyl-3-phenyl-2H-isoquinolin-1-one;
6-methyl-2-(4-methylbenzyl)-3-m-tolyl-2H-isoquinolin-1-one;
6-methyl-2-(4-methylbenzyl)-3-phenyl-2H-isoquinolin-1-one;
7-chloro-2-(2,4-dimethylbenzyl)-3-phenyl-2H-isoquinolin-1-one;
2-(4-methylbenzyl)-3-phenyl-2H-isoquinolin-1-one;
2-benzyl-3-phenyl-2H-isoquinolin-1-one;
3-(4-benzylphenyl)-2-(2,4-dimethylbenzyl)-8-methyl-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-(4′-methanesulfonyl-biphenyl-3-yl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-(3′-ethanesulfonyl-5′-trifluoromethyl-biphenyl-3-yl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[3-(6-ethoxypyridin-3-yl)-phenyl]-2H-isoquinolin-1-one;
5-{3-[8-chloro-2-(2,4-difluorobenzyl)-1-oxo-1,2-dihydroisoquinolin-3-yl]-phenyl}-2-ethoxy-nicotinonitrile;
3-(3′,5′-bis-trifluoromethylbiphenyl-3-yl)-8-chloro-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one; and
8-chloro-3-(3′-chloro-4′-ethoxybiphenyl-3-yl)-2-(2,4-difluorobenzyl)-2H-isoquinolin-1-one.
20 . The compound of claim 16 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, halo, haloalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 2 is phenyl optionally substituted with one or more substituents selected from the group consisting of alkyl, —R 6 —OR 4 , and —R 6 —S(O) t R 4 (where t is 0 to 2); R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, cycloalkyl, heterocyclyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen or aralkyl.
21 . The compound of claim 20 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, halo, haloalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 2 is phenyl optionally substituted with one or more substituents selected from the group consisting of alkyl, —R 6 —OR 4 , and —R 6 —S(O) t R 4 (where t is 0 to 2); R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, and haloalkyl; each R 4 is independently selected from the group consisting of hydrogen, alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 6 is a direct bond; and R 7 is hydrogen or aralkyl.
22 . The compound of claim 21 selected from the group consisting of the following:
2-benzyl-3-(4-hydroxy-3,5-dimethylphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(4-hydroxy-3,5-dimethylphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(4-methoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-3-(4-hydroxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(4-hydroxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(4-hydroxy-3-methoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-[3-methyl-4-(tetrahydropyran-2-yloxy)phenyl]-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(4-hydroxy-3-methylphenyl)-2H-isoquinolin-1-one;
2-(4-methylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(4-methylsulfanylphenyl)-2H-isoquinolin-1-one;
2-(4-methyl-benzyl)-3-(4-methylsulfanylphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(3-methyl-4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
5-chloro-2-(2,4-dimethylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
5-chloro-2-(4-methylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-5-fluoro-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-5-fluoro-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-dimethylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-8-chloro-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-8-methyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
8-methyl-2-(4-methylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-8-methyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-7-methyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
7-methyl-2-(4-methylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-7-methyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-6-methyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-6-methyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
6-methyl-2-(4-methylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
7-chloro-2-(2,4-dimethylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-7-chloro-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-6-chloro-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
6-chloro-2-(2,4-dimethylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-6,8-dimethyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-6,8-dimethyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-5-methyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-5,6,7,8-tetramethyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-5-methyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-8-methoxy-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-8-fluoro-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-dichloro-benzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-benzyl-8-fluoro-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-3-(4-phenoxyphenyl)-8-trifluoromethyl-2H-isoquinolin-1-one;
2-(2,4-dimethylbenzyl)-8-methoxy-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
7,8-dichloro-2-(2,4-dimethylbenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-5-methyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
6,7-dichloro-2-(2,4-difluorobenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
8-chloro-2-(2-chloro-4-fluoro-benzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
5,6-dichloro-2-(2,4-difluorobenzyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-{4-[8-chloro-2-(2,4-difluorobenzyl)-1-oxo-1,2-dihydro-isoquinolin-3-yl]-phenoxy}-nicotinonitrile;
8-chloro-2-(2,4-difluorobenzyl)-3-(4-hydroxyphenyl)-2H-isoquinolin-1-one;
8-chloro-2-(2,4-difluorobenzyl)-3-[4-(pyrazin-2-yloxy)phenyl]-2H-isoquinolin-1-one;
2-{4-[2-(2,4-difluorobenzyl)-7-fluoro-1-oxo-1,2-dihydro-isoquinolin-3-yl]-phenoxy}-nicotinonitrile;
2-(2,4-difluorobenzyl)-7-fluoro-3-[4-(pyrazin-2-yloxy)phenyl]-2H-isoquinolin-1-one;
2-(2,4-difluorobenzyl)-7-fluoro-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one;
2-(2,4-difluorobenzyl)-5-fluoro-3-[4-(pyrazin-2-yloxy)phenyl]-2H-isoquinolin-1-one;
2-{4-[2-(2,4-difluorobenzyl)-5-fluoro-1-oxo-1,2-dihydro-isoquinolin-3-yl]-phenoxy}-nicotinonitrile; and
2-(2,4-difluorobenzyl)-5-fluoro-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one.
23 . The compound of claim 16 wherein:
n is 0 or 1; R 1 is alkyl or halo; R 2 is phenyl optionally substituted with one or more substituents selected from the group consisting of cyano, halo, haloalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —N(R 4 )C(O)R 4 ; R 3 is benzyl optionally substituted with one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, cycloalkyl, heterocyclyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, aryl, and aralkyl; each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen or aralkyl.
24 . The compound of claim 23 wherein:
n is 0 or 1; R 1 is alkyl or halo; R 2 is phenyl optionally substituted with one or more substituents selected from the group consisting of cyano, halo, haloalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —N(R 4 )C(O)R 4 ; R 3 is benzyl wherein the phenyl group is optionally substituted with one or more alkyl substituents; each R 4 is independently selected from the group consisting of hydrogen, alkyl, aryl, and aralkyl; and each R 6 is a direct bond.
25 . The compound of claim 24 selected from the group consisting of the following:
N-[4-(2-benzyl-1-oxo-1,2-dihydroisoquinolin-3-yl)phenyl]acetamide;
3-(4-aminophenyl)-2-(2,4-dimethylbenzyl)-2H-isoquinolin-1-one;
3-(3,5-bis-trifluoromethylphenyl)-2-(2,4-dimethylbenzyl)-2H-isoquinolin-1-one;
4-[2-(2,4-dimethylbenzyl)-1-oxo-1,2-dihydroisoquinolin-3-yl]benzoic acid methyl ester;
2-(2,4-dimethylbenzyl)-3-(4-methoxy-3-trifluoromethylphenyl)-2H-isoquinolin-1-one;
N-{4-[2-(2,4-dimethylbenzyl)-1-oxo-1,2-dihydroisoquinolin-3-yl]phenyl}-acetamide;
4-[2-(2,4-dimethylbenzyl)-1-oxo-1,2-dihydroisoquinolin-3-yl]benzonitrile;
2-(2,4-dimethylbenzyl)-3-(3-trifluoromethylphenyl)-2H-isoquinolin-1-one;
2-(4-methylbenzyl)-3-(3-trifluoromethylphenyl)-2H-isoquinolin-1-one;
2-benzyl-3-(3-trifluoromethylphenyl)-2H-isoquinolin-1-one;
3-(4-bromophenyl)-2-(2,4-dimethylbenzyl)-2H-isoquinolin-1-one; and
3-(4-bromophenyl)-2-(4-methylbenzyl)-2H-isoquinolin-1-one.
26 . The compound of claim 1 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 2 is aryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); R 3 is alkyl or cycloalkylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); or R 3 is heteroarylalkyl wherein the heteroaryl group of the heteroarylalkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2); each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen or aralkyl.
27 . The compound of claim 26 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, halo, haloalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 2 is phenyl optionally substituted with one or more substituents selected from the group consisting of alkyl, cyano, nitro, halo, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 3 is alkyl or cycloalkylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, cyano, nitro, halo, haloalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; each R 4 is independently selected from the group consisting of hydrogen, alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen or aralkyl.
28 . The compound of claim 27 selected from the group consisting of the following:
8-chloro-2-cyclohexylmethyl-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one; and
8-chloro-2-(2,2-dimethyl-propyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one.
29 . The compound of claim 26 wherein:
n is 0 to 4; each R 1 is independently selected from the group consisting of alkyl, halo, haloalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; R 2 is phenyl optionally substituted with one or more substituents selected from the group consisting of alkyl, cyano, nitro, halo, haloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; or R 3 is heteroarylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , and —R 6 —C(O)N(R 4 ) 2 ; each R 4 is independently selected from the group consisting of hydrogen, alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl; each R 6 is a direct bond or a straight or branched alkylene chain; and R 7 is hydrogen or aralkyl.
30 . The compound of claim 29 selected from the group consisting of:
8-chloro-3-(4-phenoxyphenyl)-2-pyridin-3-ylmethyl-2H-isoquinolin-1-one-trifluoroacetic acid salt;
8-chloro-2-(5-methyl-furan-2-ylmethyl)-3-(4-phenoxyphenyl)-2H-isoquinolin-1-one; and
8-chloro-3-(4-phenoxyphenyl)-2-thiophen-2-ylmethyl-2H-isoquinolin-1-one.
31 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula (I):
wherein:
n is 0 to 4;
each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
R 2 is alkynyl optionally substituted with —Si(R 4 ) 3 , hydroxyalkyl, optionally substituted aryl, or optionally substituted cycloalkyl,
or R 2 is aryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 2 is heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
R 3 is alkyl or cycloalkylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 3 is aralkyl wherein the aryl group of the aralkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 3 is heteroarylalkyl wherein the heteroaryl group of the heteroarylalkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl;
each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl;
each R 6 is a direct bond or a straight or branched alkylene chain; and
R 7 is hydrogen or aralkyl;
as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers; or as a solvate or polymorph; or as a pharmaceutically acceptable salt thereof;
with the following provisos:
(a) when n is 0, R 7 is hydrogen and R 3 is either benzyl or 4-methylbenzyl, R 2 can not be 4-chlorophenyl, 4-methoxyphenyl, or 3-chlorophenyl;
(b) when R 7 is hydrogen, n is 0 or 1, R 1 is chloro, methyl, trifluoromethyl or methoxy, and R 3 is methyl, R 2 can not be unsubstituted furanyl or thiophenyl optionally substituted by methyl;
(c) when R 7 is hydrogen, n is 0, 1 or 2, each R 1 is independently halo, trifluoromethyl, an alkyl group of 1 to 3 carbons or —R 6 —OR 4 where R 6 is a direct bond and R 4 is an alkyl group of 1 to 3 carbons, and R 3 is an alkyl group of 1 to 3 carbons, R 2 can not be phenyl optionally substituted by halo, an alkyl group of 1 to 3 carbons or —R 6 —OR 4 where R 6 is a direct bond and R 4 is an alkyl group of 1 to 4 carbons;
(d) when R 7 is hydrogen, n is 0 or 1, R 1 is halo, methyl or methoxy, and R 3 is methyl, R 2 can not be oxazole.
32 . A method of treating a disease-state in a mammal where the disease-state is associated with the activity of a nuclear receptor, wherein the method comprises administering to the mammal a therapeutically effective amount of a compound of formula (I):
wherein:
n is 0 to 4;
each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
R 2 is alkynyl optionally substituted with —Si(R 4 ) 3 , hydroxyalkyl, optionally substituted aryl, or optionally substituted cycloalkyl,
or R 2 is aryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 2 is heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
R 3 is alkyl or cycloalkylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 3 is aralkyl wherein the aryl group of the aralkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 3 is heteroarylalkyl wherein the heteroaryl group of the heteroarylalkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl;
each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl;
each R 6 is a direct bond or a straight or branched alkylene chain; and
R 7 is hydrogen or aralkyl;
as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers; or as a solvate or polymorph; or as a pharmaceutically acceptable salt thereof.
33 . A method of treating, preventing or ameliorating one or more symptoms or causes of atherosclerosis in a mammal, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound of formula (I):
wherein:
n is 0 to 4;
each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
R 2 is alkynyl optionally substituted with —Si(R 4 ) 3 , hydroxyalkyl, optionally substituted aryl, or optionally substituted cycloalkyl,
or R 2 is aryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 2 is heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
R 3 is alkyl or cycloalkylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)R 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 3 is aralkyl wherein the aryl group of the aralkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 3 is heteroarylalkyl wherein the heteroaryl group of the heteroarylalkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl;
each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl;
each R 6 is a direct bond or a straight or branched alkylene chain; and
R 7 is hydrogen or aralkyl;
as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers; or as a solvate or polymorph; or as a pharmaceutically acceptable salt thereof.
34 . A method of treating, preventing or ameliorating one or more symptoms or causes of hyperlipidemia in a mammal, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound of formula (I):
wherein:
n is 0 to 4;
each R 1 is independently selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, cyano, nitro, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
R 2 is alkynyl optionally substituted with —Si(R 4 ) 3 , hydroxyalkyl, optionally substituted aryl, or optionally substituted cycloalkyl,
or R 2 is aryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 2 is heteroaryl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
R 3 is alkyl or cycloalkylalkyl optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, cyano, nitro, halo, haloalkyl, haloalkenyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 3 is aralkyl wherein the aryl group of the aralkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
or R 3 is heteroarylalkyl wherein the heteroaryl group of the heteroarylalkyl substituent is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkenyl, aryl, aralkyl, cyano, nitro, halo, haloalkyl, haloalkenyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl, optionally substituted heteroarylalkyl, —R 6 —OR 4 , —R 6 —N(R 4 ) 2 , —R 6 —C(O)OR 4 , —R 6 —C(O)N(R 4 ) 2 , —R 6 —N(R 4 )C(O)R 4 , —R 6 —N(R 4 )C(O)OR 5 , —R 6 —N[S(O) t R 4 ] 2 (where t is 0 to 2), —R 6 —N(R 4 )(S(O) t R 4 ) (where t is 0 to 2), —R 6 —S(O) t R 4 (where t is 0 to 2), and —R 6 —S(O) p N(R 4 ) 2 (where p is 1 or 2);
each R 4 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl and optionally substituted heteroaryl;
each R 5 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, haloalkyl, hydroxyalkyl, cycloalkyl, cycloalkylalkyl, and aralkyl;
each R 6 is a direct bond or a straight or branched alkylene chain; and
R 7 is hydrogen or aralkyl;
as a single stereoisomer, a mixture of stereoisomers, or as a racemic mixture of stereoisomers; or as a solvate or polymorph; or as a pharmaceutically acceptable salt thereof.Join the waitlist — get patent alerts
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