Patent ID: 6159980
Filing Date: 2000-12-12
Classification: A61P,C07D

Abstract:
A compound of Formula I: ##STR14## or a pharmaceutically acceptable salt form thereof, wherein: Z is CR.sup.2 ;Y is NR.sup.4, O, S(O).sub.n ;Ar is phenyl, naphthyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,3,5-triazinyl, 1,2,4-triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, indolinyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, benzothiazolyl, indazolyl, isoxazolyl or pyrazolyl, each substituted with 0 to 4 R.sup.5 groups; wherein Ar is attached to Y through an unsaturated carbon;R.sup.1 is H, halo, 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.8 cycloalkyl, C.sub.1 -C.sub.4 haloalkyl, aryl, heterocyclyl, --CN, --OR.sup.7, --SH, --S(O).sub.n R.sup.13, --COR.sup.7, --CONR.sup.6 R.sup.7, --CO.sub.2 R.sup.7, --OC(O)R.sup.13, --NR.sup.8 COR.sup.7, --N(COR.sup.7).sub.2, --NR.sup.8 CONR.sup.6 R.sup.7, --NR.sup.8 CO.sub.2 R.sup.7, or --NR.sup.6 R.sup.7, wherein C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl or C.sub.3 -C.sub.8 cycloalkyl is each substituted with 0 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, --CN, --OR.sup.7, --SH, --S(O).sub.n R.sup.13, --COR.sup.7, --CO.sub.2 R.sup.7, --OC(O)R.sup.13, --NR.sup.8 COR.sup.7, --N(COR.sup.7).sub.2, --NR.sup.8 CONR.sup.6 R.sup.7, --NR.sup.8 CO.sub.2 R.sup.7, --NR.sup.6 R.sup.7, --CONR.sup.6 R.sup.7, aryl and heterocyclyl;R.sup.2 is 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, halo, --CN, C.sub.1 -C.sub.4 haloalkyl, --NR.sup.9 R.sup.10, --NR.sup.9 COR.sup.10, --NR.sup.9 CO.sub.2 R.sup.10, --OR.sup.11, --SH or --S(O).sub.n R.sup.12 ;R.sup.3 is 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.8 cycloalkyl, C.sub.1 -C.sub.4 haloalkyl, aryl, heterocyclyl, --CN, --OR.sup.7, --S(O).sub.2 R.sup.13, --COR.sup.7, --CO.sub.2 R.sup.7, --NR.sup.8 COR.sup.7, --N(COR.sup.7).sub.2, --NR.sup.8 CONR.sup.6 R.sup.7, --CONR.sup.6 R.sup.7, --NR.sup.8 CO.sub.2 R.sup.7, or --NR.sup.6 R.sup.7, wherein C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.2 -C.sub.10 alkynyl or C.sub.3 -C.sub.8 cycloalkyl is each substituted with 0 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, --CN, --OR.sup.7, --S(O).sub.n R.sup.13, --COR.sup.7, --CO.sub.2 R.sup.7, --NR.sup.8 COR.sup.7, --N(COR.sup.7).sub.2, --NR.sup.8 CONR.sup.6 R.sup.7, --NR.sup.8 CO.sub.2 R.sup.7, --NR.sup.6 R.sup.7, --CONR.sup.6 R.sup.7, aryl and heterocyclyl, with the proviso that when R.sup.3 is aryl, Ar is not imidazolyl;R.sup.4 is H, C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl or C.sub.2 -C.sub.6 alkynyl, wherein C.sub.2 -C.sub.6 alkenyl or C.sub.2 -C.sub.6 alkynyl is optionally substituted with C.sub.1 -C.sub.4 alkyl or C.sub.3 -C.sub.6 cycloalkyl and wherein C.sub.1 -C.sub.6 alkyl is optionally substituted with C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.1 -C.sub.4 haloalkyl, --OR.sup.7, --S(O).sub.n R.sup.12, --CO.sub.2 R.sup.7, --NR.sup.6 R.sup.7 or --NR.sup.9 COR.sup.10 ;R.sup.5 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, aryl, heterocyclyl, --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, --OR.sup.7, --COR.sup.7, --CO.sub.2 R.sup.7, --CONR.sup.6 R.sup.7, --CON(OR.sup.9)R.sup.7, --SH, and --S(O).sub.n R.sup.13,wherein 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 substituted with 0 to 3 substituents independently selected at each occurrence from C.sub.1 -C.sub.4 alkyl, --NO.sub.2, halo, --CN, --OR.sup.7, --COR.sup.7, --CO.sub.2 R.sup.7, --CONR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.8 COR.sup.7, --NR.sup.8 CO.sub..sub.2 R.sup.7 and --S(O).sub.n R.sup.13 ;R.sup.6 and R.sup.7 are independently selected at each occurrence from H, 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)-, heterocyclyl, heterocyclyl(C.sub.1 -C.sub.4 alkyl)-, morpholinoethyl, morpholinopropyl and morpholinobutyl; or NR.sup.6 R.sup.7 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methylpiperazine, morpholine or thiomorpholine;wherein C.sub.1 -C.sub.4 alkyl, may be substituted with 0 to 2 substituents independently selected at each occurrence from --OH or C.sub.1 -C.sub.4 alkoxy groups;R.sup.8 is independently at each occurrence H or C.sub.1 -C.sub.4 alkyl;R.sup.9 and R.sup.10 are independently at each occurrence selected from H, C.sub.1 -C.sub.4 alkyl and C.sub.3 -C.sub.6 cycloalkyl;R.sup.11 is 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, C.sub.1 -C.sub.4 haloalkyl or --NR.sup.6 R.sup.7 ;R.sup.13 is 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, --NR.sup.6 R.sup.7, aryl, aryl(C.sub.1 -C.sub.4 alkyl)-, heterocyclyl or heterocyclyl(C.sub.1 -C.sub.4 alkyl)-;R.sup.14 is 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, --NR.sup.15 R.sup.16 ;R.sup.15 and R.sup.16 are independently selected at each occurrence from H, 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 and C.sub.4 -C.sub.12 cycloalkylalkyl; or --NR.sup.15 R.sup.16 taken together as a whole is piperidine, pyrrolidine, piperazine, N-methyl-piperazine, morpholine or thiomorpholine;aryl is phenyl, biphenyl or naphthyl, each substituted with 0 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, --CN, --OR.sup.15, --SH, --S(O).sub.n R.sup.14, --COR.sup.15, --CO.sub.2 R.sup.15, --OC(O)R.sup.14, --NO.sub.2, --NR.sup.8 COR.sup.15, --N(COR.sup.l5).sub.2, --NR.sup.8 CONR.sup.15 R.sup.16, --NR.sup.8 CO.sub.2 R.sup.15, --NR.sup.15 R.sup.16 and --CONR.sup.15 R.sup.16 ;heterocyclyl is pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl or pyrazolyl, each substituted with 0 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, --CN, --OR.sup.15, --SH, --S(O).sub.n R.sup.14, --COR.sup.15, --CO.sub.2 R.sup.15, --OC(O)R.sup.14, --NO.sub.2, --NR.sup.8 COR.sup.15, --N(COR.sup.15).sub.2, --NR.sup.8 CONR.sup.15 R.sup.16, --NR.sup.8 CO.sub.2 R.sup.15, --NR.sup.15 R.sup.16 and --CONR.sup.15 R.sup.16 ; andn is independently at each occurrence 0, 1 or 2.