Patent ID: 6160000
Filing Date: 2000-12-12
Classification: C07D

Abstract:
A compound having the formula I or Ia: ##STR49## or a pharmaceutically acceptable salt thereof, wherein: A is optionally a single or double bonded carbon or a single or double bond;R.sup.1 is selected from a group consisting of: H, C.sub.1-15 alkyl, C.sub.2-15 alkenyl, C.sub.2-15 alkynyl and C.sub.3-10 cycloalkyl, said alkyl, alkenyl, alkynyl, and cycloalkyl optionally substituted with 1 to 3 groups of R.sup.a ;R.sup.2 is selected from a group consisting of: H, C.sub.1-15 alkyl, C.sub.2-15 alkenyl, OR.sup.3, CO.sub.2 alkyl, COalkyl, OH, --OC(O)R.sup.3, C.sub.2-15 alkynyl, C.sub.5-10 aryl, and C.sub.5-10 heteroaryl, wherein said heteroaryl is selected from the group consisting of tetrazole, benzisoxazole, indole, benzothiophene, and benzofuran, said alkyl, alkenyl, alkynyl, aryl and heteroaryl optionally substituted with 1 to 3 groups of R.sup.a ;R.sup.3 is selected from a group consisting of: H, NHR.sup.1, NHacyl, C.sub.1-15 alkyl, C.sub.2-15 alkenyl, C.sub.1-15 alkoxy, CO.sub.2 alkyl, OH, C.sub.2-15 alkynyl, C.sub.5-10 aryl, and C.sub.5-10 heteroaryl, wherein said heteroaryl is selected from the group consisting of tetrazole, benzisoxazole, indole, benzothiophene, and benzofuran, said alkyl, alkenyl, alkynyl, aryl and heteroaryl optionally substituted with 1 to 3 groups of R.sup.a ;R.sup.4 is selected from the group consisting of: R.sup.2, --D--R.sup.5 or ##STR50## R.sup.5 is selected from the group consisting of: C.sub.5-10 aryl and C.sub.5-10 heteroaryl, wherein said heteroaryl is selected from the group consisting of tetrazole, benzisoxazole, indole, benzothiophene, and benzofuran, said aryl and heteroaryl optionally substituted with 1 to 3 groups of R.sup.a ;W is --CR.sup.6 R.sup.7 --, or ##STR51## R.sup.8 is selected from the group consisting of CR.sup.6 R.sup.7, O, NR.sup.6, and S(O).sub.P ;R.sup.6 and R.sup.7 are independently selected from the group consisting of H and C.sub.1-6 alkyl;B is a 5 membered heterocycle, wherein said heterocycle and the aromatic ring to which it is fused represent benzisoxazole, indole, benzothiophene, or benzofuran, the heterocycle being optionally unsubstituted or substituted with 1 to 3 groups of R.sup.a ;D is selected from the group consisting of: O, S(O).sub.p and NR.sup.1 ;X.sup.1 and X.sup.2 are independently selected from a group consisting of: H, OH, C.sub.1-15 alkyl, C.sub.2-15 alkenyl, C.sub.2-15 alkynyl, halo, OR.sup.3, C.sub.5-10 aryl, C.sub.5-10 aralkyl, C.sub.5-10 heteroaryl and C.sub.1-10 acyl, wherein said heteroaryl is selected from the group consisting of tetrazole, benzisoxazole, indole, benzothiophene, and benzofuran, said alkyl, alkenyl, alkynyl, aryl and heteroaryl optionally substituted with 1 to 3 groups of R.sup.a ;R.sup.a represents a member selected from the group consisting of: halo, aryl, heteroaryl, CF.sub.3, OCF.sub.3, CN, NO.sub.2, R.sup.3, OR.sup.3 ; SR.sup.3, S(O)R.sup.3, SO.sub.2 R.sup.3, NR.sup.3 R.sup.3, NR.sup.3 COR.sup.3, NR.sup.3 CO.sub.2 R.sup.3, NR.sup.3 CON(R.sup.3)2, NR.sup.3 SO.sub.2 R.sup.3, COR.sup.3, CO.sub.2 R.sup.3, CON(R.sup.3).sub.2, SO.sub.2 N(R.sup.3).sub.2, and OCON(R.sup.3).sub.2 wherein said heteroaryl is selected from the group consisting of tetrazole, benzisoxazole, indole, benzothiophene, benzofuran, and 4,5,6,7-tetrahydronaphthofuran, and said aryl and heteroaryl are optionally substituted with 1 to 3 groups of halo or C1-6 alkyl;Y is selected from the group consisting of: S, --CH.sub.2 --, CO, NR.sup.1, and O, with the proviso that if A is a single or double bonded carbon or a single bond, Y is --CH.sub.2 -- or CO;Y.sup.2 is selected from the group consisting of: O, N(C.sub.1-15) alkyl, N(CO.sub.2)alkyl, N--Oalkyl, N--Oacyl and N--OH, with the proviso that if Y.sup.2 is O and R.sup.3 is CH.sub.3 then n is 2;Y.sup.1 is selected from the group consisting of: O, NH, S(O)p and CH.sub.2 ;Z is selected from the group consisting of: CO.sub.2 R.sup.3, CONHSO.sub.2 Me, CONH.sub.2 and 5-(1H-tetrazole); or(Z-W).sub.t or (Z-W).sub.v together with X.sup.1 can form a 6 membered ring, said ring being a carbocycle, optionally substituted with 1 to 3 groups of R.sup.a ; in the case where (Z-W).sub.t is used v is 0 or 1; in the case where (Z-W).sub.v is used t is 0 or 1; with the proviso that if A is a double bond, then Y is O, CO, or CH2; and with the further proviso that if A is a double bond and Y is O, then the (Z-W).sub.t substituent and X.sup.1 are used to form a 4,5,6,7-tetrahydronaphthofuran group , and v is 0 or 1;t and v are independently 0 or 1 such that t+v=1;n is 2-4,p is 0-2; andat least one substituent or the combination of B and the aromatic ring to which B is fused is benzisoxazole.