Patent ID: 6191131
Filing Date: 2001-02-20
Classification: C07D

Abstract:
A compound of Formula (1): ##STR48##and isomers thereof, stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, and pharmaceutically acceptable salt forms thereof wherein:Ar is selected from phenyl, naphthyl, pyridyl, pyrimidinyl, triazinyl, furanyl, thienyl, benzothienyl, benzofuranyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, indanyl, 1,2-benzopyranyl, 3,4-dihydro-1,2-benzopyranyl, tetralinyl, each Ar optionally substituted with 1 to 5 R.sup.4 groups and each Ar is attached to an unsaturated carbon atom;R.sup.1 is independently selected at each occurrence from H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, halo, CN, C.sub.1 -C.sub.4 haloalkyl, C.sub.1 -C.sub.12 hydroxyalkyl, C.sub.2 -C.sub.12 alkoxyalkyl, C.sub.2 -C.sub.10 cyanoalkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, NR.sup.9 R.sup.10, C.sub.1 -C.sub.4 alkyl-NR.sup.9 R.sup.10, NR.sup.9 COR.sup.10, OR.sup.11, SH or S(O).sub.n R.sup.12 ;R.sup.2 is selected from H, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, C.sub.1 -C.sub.4 hydroxyalkyl, halo, CN, --NR.sup.6 R.sup.7, NR.sup.9 COR.sup.10, --NR.sup.6 S(O).sub.n R.sup.7, S(O).sub.n NR.sup.6 R.sup.7, C.sub.1 -C.sub.4 haloalkyl, --OR.sup.7, SH or --S(O).sub.n R.sup.12 ;R.sup.3 is selected from NR.sup.6a R.sup.7a and OR.sup.7 ;R.sup.4 is independently selected at each occurrence from: C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.12 cycloalkylalkyl, NO.sub.2, halo, CN, C.sub.1 -C.sub.4 haloalkyl, NR.sup.6 R.sup.7, NR.sup.8 COR.sup.7, NR.sup.8 CO.sub.2 R.sup.7, COR.sup.7, OR.sup.7, CONR.sup.6 R.sup.7, CO(NOR.sup.9)R.sup.7, CO.sub.2 R.sup.7, or S(O).sub.n R.sup.7, where each such C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl, C.sub.3 -C.sub.6 cycloalkyl and C.sub.4 -C.sub.12 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected at each occurrence from C.sub.1 -C.sub.4 alkyl, NO.sub.2, halo, CN, NR.sup.6 R.sup.7, NR.sup.8 COR.sup.7, NR.sup.8 CO.sub.2 R.sup.7, COR.sup.7 OR.sup.7, CONR.sup.6 R.sup.7, CO.sub.2 R.sup.7, CO(NOR.sup.9)R.sup.7, or S(O).sub.n R.sup.7 ;R.sup.6, R.sup.7, R.sup.6a and R.sup.7a are independently selected at each occurrence from:H,C.sub.1 -C.sub.10 alkyl, C.sub.3 -C.sub.10 alkenyl, C.sub.3 -C.sub.10 alkynyl, C.sub.1 -C.sub.10 haloalkyl with 1-10 halogens, C.sub.2 -C.sub.8 alkoxyalkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.12 cycloalkylalkyl, C.sub.5 -C.sub.10 cycloalkenyl, or C.sub.6 -C.sub.14 cycloalkenylalkyl, each optionally substituted with 1 to 3 substituents independently selected at each occurrence from C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, halo, C.sub.1 -C.sub.4 haloalkyl, cyano, OR.sup.15, SH, S(O).sub.n R.sup.13, COR.sup.15, CO.sub.2 R.sup.15, OC(O)R.sup.13, NR.sup.8 COR.sup.15, N(COR.sup.15).sub.2, NR.sup.8 CONR.sup.16 R.sup.15, NR.sup.8 CO.sub.2 R.sup.13, NR.sup.16 R.sup.15, CONR.sup.16 R.sup.15, aryl, heteroaryl or heterocyclyl,aryl, aryl(C.sub.1 -C.sub.4 alkyl), heteroaryl, heteroaryl(C.sub.1 -C.sub.4 alkyl), heterocyclyl or heterocyclyl(C.sub.1 -C.sub.4 alkyl),alternatively, NR.sup.6 R.sup.7 and NR.sup.6a R.sup.7a are independently piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine, each optionally substituted with 1-3 C.sub.1 -C.sub.4 alkyl groups;R.sup.8 is independently selected at each occurrence from H or C.sub.1 -C.sub.4 alkyl;R.sup.9 and R.sup.10 are independently selected at each occurrence from H, C.sub.1 -C.sub.4 alkyl, or C.sub.3 -C.sub.6 cycloalkyl;R.sup.11 is selected from H, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 haloalkyl, or C.sub.3 -C.sub.6 cycloalkyl;R.sup.12 is C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 haloalkyl;R.sup.13 is selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 haloalkyl, C.sub.2 -C.sub.8 alkoxyalkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.12 cycloalkylalkyl, aryl, aryl(C.sub.1 -C.sub.4 alkyl)-, heteroaryl or heteroaryl(C.sub.1 -C.sub.4 alkyl)-;R.sup.15 and R.sup.16 are independently selected at each occurrence from H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.10 cycloalkyl, C.sub.4 -C.sub.16 cycloalkylalkyl, except that for S(O).sub.n R.sup.15, R.sup.15 cannot be H;aryl is phenyl or naphthyl, each optionally substituted with 1 to 5 substituents independently selected at each occurrence from C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, halo, C.sub.1 -C.sub.4 haloalkyl, cyano, OR.sup.15, SH, S(O).sub.n R.sup.15, COR.sup.15, CO.sub.2 R.sup.15, OC(O)R.sup.15, NR.sup.8 COR.sup.15, N(COR.sup.15).sub.2, NR.sup.8 CONR.sup.16 R.sup.15, NR.sup.8 CO.sub.2 R.sup.15, NR.sup.16 R.sup.15, and CONR.sup.16 R.sup.15 ;heteroaryl is pyridyl, pyrimidinyl, triazinyl, furanyl, pyranyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, isoxazolyl, pyrazolyl, 2,3-dihydrobenzothienyl or 2,3-dihydrobenzofuranyl, each being optionally substituted with 1 to 5 substituents independently selected at each occurrence from C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, halo, C.sub.1 -C.sub.4 haloalkyl, cyano, OR.sup.15, SH, S(O).sub.n R.sup.15, --COR.sup.15, CO.sub.2 R.sup.15, OC(O)R.sup.15, NR.sup.8 COR.sup.15, N(COR.sup.15).sub.2, NR.sup.8 CONR.sup.16 R.sup.15, NR.sup.8 CO.sub.2 R.sup.15, NR.sup.16 R.sup.15, and CONR.sup.16 R.sup.15 ;heterocyclyl is saturated or partially saturated heteroaryl, optionally substituted with 1 to 5 substituents independently selected at each occurrence from C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, halo, C.sub.1 -C.sub.4 haloalkyl, cyano, OR.sup.15, SH, S(O).sub.n R.sup.15, COR.sup.15, CO.sub.2 R.sup.15, OC(O)R.sup.15, NR.sup.8 COR.sup.15, N(COR.sup.15).sub.2, NR.sup.8 CONR.sup.16 R.sup.15, NR.sup.8 CO.sub.2 R.sup.15, NR.sup.15 R.sup.16, and CONR.sup.16 R.sup.15 ;n is independently at each occurrence 0, 1 or 2;with the provisos that:(1) when R.sup.2 is H and R.sup.3 is --OR.sup.7 and R.sup.7 is H, then R.sup.1 is not H, OH or SH;(2) when R.sup.1 is CH.sub.3 or C.sub.2 H.sub.5 and R.sup.2 is H, and R.sup.3 is OH, NHC.sub.4 H.sub.9, or N(C.sub.2 H.sub.5).sub.2, then Ar is not phenyl or m-CH.sub.3 -phenyl;(3) when R.sup.2 is H and Ar is pyridyl, pyrimidinyl or pyrazinyl, and R.sup.3 is NR.sup.6a R.sup.7a, then R.sup.6a and R.sup.7a are not H or alkyl;(4) when R.sup.2 is SO.sub.2 NR.sup.6 R.sup.7, then R.sup.3 is not OH; and(5) when R.sup.2 is --NR.sup.6 SO.sub.2 R.sup.7 or --SO.sub.2 NR.sup.6 R.sup.7, then R.sup.3 is not OH.