Patent ID: 6063796
Filing Date: 2000-05-16
Classification: A61P,C07D

Abstract:
A compound represented by formula I: ##STR120## as well as pharmaceutically acceptable salts and hydrates 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.1-5 alkyl)--, aryl(C.sub.0 -C.sub.5 alkyl)-K-(C.sub.1 -C.sub.5 alkyl)--, and (C.sub.3-7 cycloalkyl)(C.sub.0-5 alkyl)-K-(C.sub.1-5 alkyl)--,the alkyl portions of which being 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,aryl is selected from the group consisting of: phenyl, naphthyl, biphenyl, quinolinyl, isoquinolinyl, indolyl, azaindole, pyridyl, benzothienyl, benzofuranyl, thiazolyl and benzimidazolyl, unsubstituted or substituted with: 1 to 3 C.sub.1-6 alkyl groups, 1 to 3 halo groups, 1 to 2 --OR.sup.2 groups, methylenedioxy, --S(O).sub.m R.sup.2, 1 to 2--CF.sub.3, --OCF.sub.3 or NO.sub.2 groups, --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.sub.2 phenyl, or --N(R.sup.2)SO.sub.2 R.sup.2 ;K is selected from the group consisting of: --O--, --S(O).sub.m --, --N(R.sup.2)C(O)--, --C(O)N(R.sup.2)--, --CR.sup.2 .dbd.CR.sup.2 -- and --C.tbd.C--;R.sup.1a is selected from the group consisting of: H and C.sub.1-3 alkyl;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;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 when two R.sup.2 groups are present they may be taken together with the atom to which they are attached and with any intervening atoms to represent a C.sub.3-8 ring, said ring optionally including O, S or NR.sup.3a, where R.sup.3a is hydrogen, or C.sub.1-6 alkyl, said C.sub.1-6 alkyl being optionally substituted by OH;and when R.sup.2 represents C.sub.1-8 alkyl, it may be substituted by 1 to 5 halo groups, S(O).sub.m R.sup.2a, 1 to 3 OR.sup.2a groups or C(O)OR.sup.2a ;R.sup.2a is selected from the group consisting of: H and C.sub.1 -C.sub.8 alkyl, optionally substituted with OH;Z.sup.1 is selected from the group consisting of: --O--, --CH.sup.2 -- and --NR.sup.2a ;Z.sup.2 is selected from the group consisting of: --O--, --CH.sub.2 --, --CHR.sup.2b -- and --NR.sup.2b ;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, --(CH.sub.2).sub.n OH and --(CH.sub.2).sub.n OR.sup.2 ;W is selected from the group consisting of: H, C.sub.1-8 alkyl, --(CH.sub.2).sub.t -aryl, wherein aryl is selected from phenyl, biphenyl and naphthyl, --(CH.sub.2).sub.t -heteroaryl wherein heteroaryl is selected from tetrazolyl, oxadiazolyl, thiadiazolyl, triazolyl and pyrazinyl, --(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 N(R.sup.2)C(O)R.sup.2, --(CH.sub.2).sub.q C(O)N(R.sup.2).sub.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, and --(CH.sub.2).sub.q S(O).sub.m R.sup.2,wherein the heteroaryl portions thereof are optionally substituted with halo, R.sup.2, N(R.sup.2).sub.2 or OR.sup.2, and R.sup.2, (CH.sub.2).sub.q and (CH.sub.2).sub.t are optionally substituted with 1 to 2 of C.sub.1-4 alkyl, OH, OC.sub.1-8 alkyl, O(CH.sub.2).sub.t -aryl, OC.sub.3-7 cycloalkyl, CO.sub.2 H, CO.sub.2 C.sub.1-8 alkyl, CO.sub.2 (CH.sub.2).sub.t -aryl, CO.sub.2 C.sub.3-7 cycloalkyl or 1-3 halo groups, andsaid aryl portion is further optionally substituted with 1 to 3 of halogen, --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;Q represents a member selected from the group consisting of: ##STR121## wherein x and y are independently 0, 1, 2, 3, 4, 5 or 6; V is selected from the group consisting of --N(R.sup.6a)--, --S(O).sub.m --, --O--, --CONR.sup.2 -- and --NR.sup.2 CO--;R.sup.6a is selected from the group consisting of hydrogen, C.sub.1-8 alkyl, R.sup.2 C(O)-- and R.sup.2 SO.sub.2 --;R.sup.7 and R.sup.7a are independently selected from the group consisting of hydrogen, C.sub.1-6 alkyl, CF.sub.3 and aryl;R.sup.8 is selected from the group consisting of --NR.sup.4 R.sup.5, --N(.dbd.NR.sup.9)NR.sup.10 and --N.sup.+ (R.sup.4).sub.3,wherein 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(.dbd.O)N(R.sup.2).sub.2, --C(.dbd.O)R.sup.2, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl and (CH.sub.2).sub.t -cyclopropyl,or R.sup.4 and R.sup.5 taken together represent --(CH.sub.2).sub.d --L.sub.a (CH.sub.2).sub.e -- where 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 1 to 3, said heteroaryl and R.sup.2 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;E is selected from the group consisting of: --SO.sub.2 --, --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 --;R.sup.9 and R.sup.10 are independently H or C.sub.1-8 alkyl, or are optionally taken together and represent a C.sub.3-8 cyclic ring, which is optionally interrupted by O, S(O).sub.m or NR.sup.2a ;B is ##STR122## where attachment points are indicated by lines external to the rings which are optionally substituted by C.sub.1-6 alkyl and where R.sup.2 and (CH.sub.2).sub.q are described above; ##STR123## 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., --C(R.sup.11).sub.1-2 .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 -C.sub.8 alkyl, --(CH.sub.2).sub.p OR.sup.2, --(CH.sub.2).sub.p N(R.sup.2).sub.2, (CH2).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 -C.sub.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 where heteroaryl is tetrazole, oxadiazole, imidazole or triazole which is optionally substituted with R.sup.2, OR.sup.2 or N(R.sup.2).sub.2 and where p is 0-3;A is a fused aromatic ring, having 6 atoms, and containing 0 heteroatoms, optionaly substituted with 1-3 groups selected from: C.sub.1-6 alkyl, halo, --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.sub.2 phenyl, N(R.sup.2)C(O)N(R.sup.2) and --N(R.sup.2)SO.sub.2 R.sup.2 ;m is an integer from 0 to 2;n is an integer from 0 to 3;q is an integer from 0 to 3; andt is an integer from 0 to 3.