Patent ID: 6103737
Filing Date: 2000-08-15
Classification: A61P,C07D,Y10S

Abstract:
A method of treating affective disorder, anxiety or depression in mammals, comprising: administering to the mammal a therapeutically effective amount of a compound of formula (I): ##STR13## or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:Y is CR.sup.2 or N;Z is CH or N;K is CR.sup.5 or N;R.sup.1 is C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, chloro, fluoro, cyano, or trifluoromethyl;R.sup.2 taken together with R.sup.4 is --E--F--, where E and F are independently CR.sup.9 and CR.sup.9a ; or R.sup.2 taken together with R.sup.4 is --A.dbd.D--, where A and D are each independently CH, CR.sup.10 or N; provided that --A.dbd.D-- may not be --CH.dbd.N-- or --CR.sup.10 .dbd.N-- oriented in such a way as to form a pyrazole ring, but may be --CH.dbd.N-- or --CR.sup.10 .dbd.N-- oriented in such a way as to form an imidazole ring; or R.sup.2 taken together with R.sup.4 is --A--D-- where A is NR.sup.9 and D is C.dbd.O oriented in such a way as to form an imidazolone;R.sup.3 is phenyl which is substituted on 1-4 ring carbons of the phenyl with R.sup.8, napthyl which is substituted on 1-4 ring carbons of the napthyl with R.sup.8, pyridinyl which is substituted on 1-4 ring carbons of the pyridine with R.sup.8 or pyrimidinyl substituted on 1-4 ring carbons of the pyrimidine with R.sup.8 ;R.sup.4 is C.sub.1 -C.sub.4 alkyl, allyl, or propargyl, where C.sub.1 -C.sub.4 alkyl is optionally substituted with C.sub.3 -C.sub.6 cycloalkyl, OH, --OR.sup.9, --S(O).sub.n R.sup.9 or --CO.sub.2 R.sup.9 ;R.sup.5 represents 1-4 substituents on ring carbons each of which may be independently 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.10 cycloalkylalkyl, halo, nitro, cyano, --NR.sup.6 R.sup.7, --OR.sup.7, --COR.sup.7, --C(O)NR.sup.6 R.sup.7, --C(NOR.sup.9)R.sup.7, or --S(O).sub.n R.sup.7, where 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.10 cycloalkylalkyl are optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, nitro, cyano, --NR.sup.6 R.sup.7, --OR.sup.7, --COR.sup.7, --C(O)NR.sup.6 R.sup.7, --S(O).sub.n R.sup.7, and --C(NOR.sup.9)R.sup.7 and two R.sup.5 moieties taken together may comprise --CR.sup.9 R.sup.9a CR.sup.9 R.sup.9a O--, --CR.sup.9 R.sup.9a CR.sup.9 R.sup.9a CR.sup.9 R.sup.9a O--, or --CR.sup.9 .dbd.CR.sup.9a O--;R.sup.6 and R.sup.7 are independently at each occurrence selected from the group consisting of H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, --(CH.sub.2).sub.m -phenyl, and --(CH.sub.2).sub.m -heteroaryl; all optionally substituted with 1-3 R.sup.11 's;R.sup.8 is independently at each occurrence selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, phenyl, heteroaryl, halo, nitro, cyano, --NR.sup.6 R.sup.7, --OR.sup.7, --COR.sup.7, --CO.sub.2 R.sup.7, --C(O)NR.sup.6 R.sup.7, --OC(O)NR.sup.6 R.sup.7, --NR.sup.9 C(O)NR.sup.6 R.sup.7, --NR.sup.6 C(O)R.sup.7, --C(NOR.sup.9)R.sup.7, --S(O).sub.n R.sup.7, --NR.sup.9 SO.sub.2 R.sup.7, and --SO.sub.2 NR.sup.6 R.sup.7, and where C.sub.1 -C.sub.6 alkyl, C.sub.2 -C.sub.6 alkenyl, C.sub.2 -C.sub.6 alkynyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.4 -C.sub.10 cycloalkylalkyl, and phenyl are optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, nitro, cyano, --NR.sup.6 R.sup.7, --OR.sup.7, --COR.sup.7, --C(O)NR.sup.6 R.sup.7, --S(O).sub.n R.sup.7, --C(NOR.sup.9)R.sup.7, --NR.sup.9 SO.sub.2 R.sup.7, and --SO.sub.2 NR.sup.6 R.sup.7 ; provided that when R.sup.3 is pyridinyl, at least one R.sup.8 is other than methyl; further provided that when R.sup.3 is phenyl, at least one R.sup.8 is other than unsubstituted phenyl;R.sup.9 and R.sup.9a is H or C.sub.1 -C.sub.4 alkyl;R.sup.10 is C.sub.1 -C.sub.4 alkyl, halo, nitro, cyano, --NR.sup.9 R.sup.9a, --OR.sup.12, or --S(O).sub.n R.sup.12 ;R.sup.11 is independently at each occurrence selected from the group consisting of C.sub.1 -C.sub.3 alkyl, halo, nitro, cyano, --NR.sup.9 R.sup.9a, --OR.sup.9 --S(O).sub.n R.sup.12, --COR.sup.9, --CO.sub.2 R.sup.9, --C(O)NR.sup.9 R.sup.9a, --NR.sup.9 C(O)R.sup.9a, and --C(NOR.sup.9)R.sup.9a ;R.sup.12 is C.sub.1 -C.sub.4 alkyl;heteroaryl is pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzthiazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl or 2,3-dihydrobenzothienyl;n is independently at each occurrence 0, 1 or 2; andm is independently at each occurrence 0-6.