Patent ID: 6057338
Filing Date: 2000-05-02
Classification: A61P,C07D

Abstract:
A compound represented by formula I: ##STR136## or a pharmaceutically acceptable salt or hydrate thereof, wherein R.sup.1 is selected from the group consisting of: C.sub.1-10 alkyl, aryl, aryl(C.sub.1-6 alkyl)--, C.sub.3-7 cycloalkyl(C.sub.1-6 alkyl)--, C.sub.1-5 alkyl-K-(C.sub.1 -C.sub.5 alkyl)--, aryl(C.sub.0-5 alkyl)-K-(C.sub.1-5 alkyl)--, and C.sub.3-7 cycloalkyl(C.sub.0-5 alkyl)-K-(C.sub.1-5 alkyl)--,wherein K is --O--, --S(O).sub.m --, --N(R.sup.2)C(O)--, --C(O)N(R.sup.2)--, --CR.sup.2 .dbd.CR.sup.2 -- or --C.tbd.C--,the allyl portions of which are optionally substituted with by 1 to 5 halogen groups, S(O).sub.m R.sup.2a, 1 to 3 of OR.sup.2a groups or C(O)OR.sup.2a,and wherein aryl is selected from the group consisting of: phenyl, naphthyl, biphenyl, quinolinyl, isoquinolinyl, indolyl, azaindolyl, pyridyl, benzothienyl, benzofuranyl, thiazolyl and benzimidazolyl,said aryl groups being unsubstituted or substituted with 1 to 3 C.sub.1-6 alkyl or halo groups, 1 to 2 --OR.sup.2 groups, methylenedioxy, --S(O).sub.m R.sup.2, 1 to 2 --CF.sub.3 groups, --OCF.sub.3, --NO.sub.2, --N(R.sup.2)C(O)(R.sup.2), --C(O)OR.sup.2, --C(O)N(R.sup.2).sub.2, 1H-tetrazol-5-yl, --SO.sub.2 N(R.sup.2)(R.sup.2), --N(R.sup.2)SO.sub.2 phenyl, or --N(R.sup.2)SO.sub.2 R.sup.2 ;R.sup.2 is selected from the group consisting of: H, C.sub.1-8 alkyl, --(CH.sub.2).sub.t -aryl and C.sub.3-7 cycloalkyl, and where two R.sup.2 groups are present, they optionally are joined to form a C.sub.3 -C.sub.8 ring, optionally interrupted by O, S or NR.sup.3a, in which R.sup.3a is H or C.sub.1-6 alkyl optionally substituted by OH;t is an integer from 0 to 3;and when R.sup.2 is other than H, R.sup.2 is optionally substituted with 1 to 5 halogen groups, S(O).sub.m R.sup.2a, 1 to 3 of OR.sup.2a groups or C(O)OR.sup.2a,R.sup.2a is H or C.sub.1-3 alkyl optionally substituted by OH;m is 0, 1 or2;R.sup.1a is H or C.sub.1-3 alkyl;Z.sup.1 is selected from the group consisting of --O--, --CH.sub.2 -- and NR.sup.2a ;E is selected from the group consisting of --SO.sub.2 --, --C(O)--, --CO(C(R.sup.2).sub.2).sub.n --, --C(.dbd.N--CN)--, --C(.dbd.N--NO.sub.2)-- and --C(.dbd.N--SO.sub.2 N(R.sup.2).sub.2)--;n is an integer from 0 to 3;B is ##STR137## where attachment points are indicated by lines, ##STR138## said group being optionally substituted by C.sub.1-6 alkyl; ##STR139## represents an aromatic or non-aromatic 5-6 membered ring structure wherein:G is N,Y is --C(O)--, --C(OR.sup.11).dbd., --C(SR.sup.11).dbd., --C(NR.sup.11).dbd., or --C(R.sup.11).sub.2 --;andX is --N(R.sup.11)-- or .dbd.N--;R.sup.11 is H, C.sub.1-8 alkyl, CF.sub.3, CH.sub.2 CF.sub.3, --(CH.sub.2).sub.p OR.sup.2, --(CH.sub.2).sub.p N(R.sup.2).sub.2, --(CH.sub.2).sub.p N(R.sup.2)C(O)N(R.sup.2).sub.2, --(CH.sub.2).sub.p N(R.sup.2)C(O)R.sup.2, --(CH.sub.2).sub.2 -heteroaryl, --(CH.sub.2).sub.p N(R.sup.2)SO.sub.2 C.sub.1-4 alkyl, --(CH.sub.2).sub.p C(O)N(R.sup.2).sub.2 or --(CH.sub.2).sub.p C(O)OR.sup.2, wherein heteroaryl is selected from tetrazolyl, oxadiazolyl, imidazolyl and triazolyl, said heteroaryl being optionally substituted with R.sup.2, OR.sup.2, CF.sub.3 or N(R.sup.2).sub.2 and where p is 0-3; ##STR140## is a 6 membered fused aryl group, said aryl group being optionally substituted with 1-3 C.sub.1-6 alkyl or halo groups, --OR.sup.2, N(R.sup.2).sub.2, methylenedioxy, --S(O).sub.m R.sup.2, --CF.sub.3, --OCF.sub.3, --NO.sub.2, --N(R.sup.2)C(O)(R.sup.2), --C(O)OR.sup.2, --C(O)N(R.sup.2).sub.2, 1H-tetrazol-5-yl, --SO.sub.2 N(R.sup.2).sub.2, --N(R.sup.2)SO.sup.2 phenyl, --N(R.sup.2)C(O)N(R.sup.2).sub.2 or --N(R.sup.2)SO.sub.2 R.sup.2 ;Z.sup.2 is selected from the group consisting of --O--, --CH.sub.2 --, --CHR.sup.2b -- and --NR.sup.2b --,wherein R.sup.2b is selected from the group consisting of: H, C.sub.1-8 alkyl, --(CH.sub.2).sub.t -aryl, --(CH.sub.2).sub.n CO.sub.2 R.sup.2, --(CH.sub.2).sub.n CON(R.sup.2).sub.2 and --(CH.sub.2).sub.n OR.sup.2, and when Z.sup.2 is NR.sup.2b it can optionally be linked to R.sup.1c, Q or W to form a C5-8 ring, which is optionally interrupted by O, S(O).sub.m or NR.sup.2a ;R.sup.1c is selected from the group consisting of: H, --(CH.sub.2).sub.q SR.sup.2, --(CH.sub.2).sub.q OR.sup.2 and C.sub.1-8 alkyl;W is selected from the group consisting of: H, C.sub.1-8 alkyl, (CH.sub.2).sub.t -aryl, --(CH.sub.2).sub.q C(O)OR.sup.2, --(CH.sub.2).sub.q OR.sup.2, --(CH.sub.2).sub.q OC(O)R.sup.2, --(CH.sub.2).sub.q C(O)R.sup.2, --(CH.sub.2).sub.q C(O)(CH.sub.2).sub.t aryl, --(CH.sub.2).sub.q C(O)N(R.sup.2).sub.2, --(CH.sub.2).sub.q N(R.sup.2)C(O)R.sup.2, --(CH.sub.2).sub.q N(R.sup.2)SO.sub.2 R.sup.2, --(CH.sub.2).sub.q N(R.sup.2)C(O)N(R.sup.2).sub.2, --(CH.sub.2).sub.q OC(O)N(R.sup.2).sub.2, --(CH.sub.2).sub.q N(R.sup.2)C(O)OR.sup.2, --(CH.sub.2).sub.q N(R.sup.2)SO.sub.2 N(R.sup.2).sub.2, --(CH.sub.2).sub.q S(O).sub.m R.sup.2 and --(CH.sub.2).sub.t -heteroaryl, the heteroaryl portion of which is selected from: tetrazolyl, oxadiazolyl. thiadiazolyl, triazolyl and pyrazinyl, optionally substituted with R.sup.2, N(R.sup.2).sub.2 or OR.sup.2,and when R.sup.2 is other than H, said R.sup.2, (CH.sub.2).sub.q and the (CH.sub.2).sub.t portions of W are optionally substituted with 1 to 2 C.sub.1-4 alkyl, OR.sup.2a, C(O)OR.sup.2a or 1-3 halo groups, andthe aryl and heteroaryl portions of W being optionally substituted with 1 to 3 halo groups, --OR.sup.2, --CON(R.sup.2).sub.2, --C(O)OR.sup.2, C.sub.1-4 alkyl, --S(O).sub.m R.sup.2, N(R.sup.2).sub.2, CF.sub.3 or 1H-tetrazol-5-yl;k is 0 or 1, such that when k is 0, Q is attached directly to z.sup.2 ;Q represents a member selected from the group consisting of: ##STR141## where x and y are independently 0, 1, 2, 3, 4, 5, 6; V is an aromatic 6-12 membered mono- or bicyclic ring system or a non-aromatic 3-12 membered mono- or bicyclic ring system, optionally substituted with 1 to 2 R.sup.2 groups, 1 to 3 halo groups, --OR.sup.2, --CON(R.sup.2).sub.2,--C(O)OR.sup.2, --C.sub.1-4 alkyl, --S(O).sub.m R.sup.2, N(R.sup.2).sub.2, CF.sub.3 or 1H-tetrazol-5-yl;R.sup.7 and R.sup.7a are independently CF.sub.3 or R.sup.2 ;R.sup.8 is selected from the group consisting of--NR.sup.4 R.sup.5 --C(.dbd.NR.sup.9)N(R.sup.10).sub.2 and --N.sup.+ (R.sup.4).sub.3 ;R.sup.4 and R.sup.5 are independently selected from the group consisting of: R.sup.2, --C(.dbd.NR.sup.2)N(R.sup.2).sub.2, --C(.dbd.NCN)N(R.sup.2).sub.2, --C(.dbd.NC(O)R.sup.2)N(R.sup.2).sub.2, C(.dbd.NSO.sub.2 R.sup.2)N(R.sup.2).sub.2, --C(.dbd.NNO.sub.2)NR.sup.2, heteroaryl, --C(O)N(R.sup.2).sub.2, --C(.dbd.S)N(R.sup.2).sub.2, --C(O)R.sup.2, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl and --(CH.sub.2).sub.t -cyclopropyl, orR.sup.4 and R.sup.5 are taken together and represent--(CH.sub.2).sub.d --L.sub.a (CH.sub.2).sub.e --wherein L.sub.a is --C(R.sup.2).sub.2 --, --O--, --S(O).sub.m -- or --N(R.sup.2)--, and d and e are independently 0 to 3 such that d plus e equals 2-6,and said heteroaryl and R.sup.2 other than H being optionally substituted with 1-3 C.sub.1-6 alkyl groups, 1-7 halo groups, N(R.sup.2).sub.2, OR.sup.2, N(R.sup.2)C(O)R.sup.2, C(O)N(R.sup.2), OC(O)R.sup.2, S(O).sub.m R.sup.2, CF.sub.3, OCF.sub.3, NO.sub.2, N(R.sup.2)C(O)(R.sup.2), N(R.sup.2)C(O)N(R.sup.2).sub.2, C(O)OR.sup.2, C(O)N(R.sup.2).sub.2, SO.sub.2 N(R.sup.2).sub.2, N(R.sup.2)SO.sub.2 R.sup.2 or methylenedioxy;and R.sup.9 and R.sup.10 are independently H or C.sub.1-8 alkyl or may be taken together and represent a C.sub.5-8 ring, optionally substituted by 1-5 halo groups, OR.sup.2 or S(O).sub.m R.sup.2.