Patent ID: 6306887
Filing Date: 2001-10-23
Classification: A61P,C07D

Abstract:
A compound of Formula (1.0.0): ##STR145##and pharmaceutically acceptable salts and other prodrug derivatives thereof, wherein:A is phenyl, substituted with 0 to 3 R.sup.10 ; or is a member selected from the group consisting of --A.sup.1 --NHC(.dbd.O)NH--A.sup.2 --, --A.sup.1 --NHC(.dbd.O)O--A.sup.2 --, and --A.sup.1 --NH(NCN)NH--A.sup.2 --, where A.sup.1 and A.sup.2 is each independently selected from the group consisting of hydrogen, provided that A.sup.1 and A.sup.2 may not both be hydrogen, and phenyl substituted wish 0 to 3 R.sup.10 ;B is a member independently selected from the group consisting of the following: ##STR146## ##STR147##where the symbol ""*"" indicates the point of attachment of the moiety represented by each partial Formula (1.1.0) through (1.1.12) to the moiety ""Y"" in Formula (1.0.0); and the symbol "".fwdarw."" indicates the point of attachment of the moiety represented by each partial Formula (1.1.0) through (1.1.12) to the moiety ""E"" in Formula (1.0.0);E is a single bond; --O--; --CH.dbd.CH--; or a moiety of Formula (1.9.0): ##STR148##where R.sup.1.sub.a is hydrogen when R.sup.1 has the meaning of a mono-valent substituent; and R.sup.1.sub.a is a single bond when R.sup.1 has the meaning of a di-valent substituent;X is --O--; --S(.dbd.O).sub.q --; or --N(R.sup.14)--;Y is --C(.dbd.O)--; --C(.dbd.S)--; --S(.dbd.O).sub.2 --; or --CH(R.sup.a)--;m is an integer independently selected from 0, 1 and 2;n is an integer independently selected from 1 and 2;p is an integer independently selected from 1 and 2, provided that p must be selected as 1 where B is selected as partial Formula (1.1.2), (1.1.3), (1.1.5); (1.1.6), (1.1.7), (1.1.8), (1.1.9), (1.1.10), (1.1.11), or (1.1.12);q is an integer independently selected from 0 and 2;R is independently selected from the group consisting of -tetrazolyl; --C(.dbd.O)OR.sup.5 ; --C(.dbd.O)(CH.sub.2).sub.k C(.dbd.O)OR.sup.5 ; --C(.dbd.O)NO.; --C(.dbd.O)NH--S(.dbd.O).sub.2 R.sup.5 ; --S(.dbd.O).sub.2 --NR.sup.14 R.sup.5 ; --C(.dbd.O)NHS(.dbd.O).sub.2 R.sup.6 ; and a moiety of partial Formulas (3.0.0): ##STR149##where:k is an integer independently selected from 0, 1 and 2;R.sup.1 is independently selected from the group consisting of hydrogen; .dbd.O; .dbd.S; F; (C.sub.1 -C.sub.6) alkyl substituted with 0 to 3 R.sup.10 ; (C.sub.2 -C.sub.6) alkenyl substituted with 0 to 3 R.sup.10 ; (C.sub.2 --C.sub.6) alkynyl substituted with 0 to 3 R.sup.10 ; a (C.sub.3 --C.sub.14) carbocyclic ring system substituted with 0 to 3 R.sup.12 ; aryl substituted with 0 to 3 R.sup.12 ; and aryl(C.sub.1 -C.sub.1) alkyl wherein said aryl and alkyl are substituted with 0 to 3 R.sup.12 ; heterocyclyl as defined herein, substituted with 0 to 3 R.sup.12 ; and heterocyclyl(C.sub.1 -C.sub.1) alkyl as defined herein, wherein said heterocyclyl and alkyl are substituted with 0 to 3 R.sup.12 ; C(.dbd.O)NR.sup.8 R.sup.9 ; and C(.dbd.O)R.sup.8 ;R.sup.2 and R.sup.3 are each independently selected from the group consisting of hydrogen; (C.sub.1 -C.sub.1) alkyl substituted with 0 to 3 R.sup.13 ; (C.sub.2 --C.sub.6) alkenyl substituted with 0 to 3 R.sup.13 ; a (C.sub.3 --C.sub.14) carbocyclic ring system substituted with 0 to 3 R.sup.13 ; (C.sub.1 -C.sub.1) alkoxycarbonylamino-(C.sub.1 -C.sub.1)alkyl-; (C.sub.1 -C.sub.1)alkylthio-(C.sub.1 -C.sub.1)alkyl-; (C.sub.1 -C.sub.1) alkylsulfonyl-(C.sub.1 -C.sub.1)alkyl-; hydroxy(C.sub.1 -C.sub.1) alkylthio-(C.sub.1 -C.sub.1)alkyl-; (C.sub.1 -C.sub.1) alkylcarbonylamino-(C.sub.1 -C.sub.1)alkyl-; (C.sub.1 -C.sub.4) alkylsulfonylamino-(C.sub.1 -C.sub.4) alkyl-; (C.sub.1 -C.sub.1) alkylsulfonylaminocarbonyl-(C.sub.1 -C.sub.1) alkyl-; and a heterocyclyl ring as defined herein, substituted with 0 to 3 R.sup.13 ;provided thatR.sup.2 and R.sup.3 are each defined as above; or they are taken together as defined below; or one of them is taken together with R.sup.4 as defined below, in which case the other has the meaning of hydrogen or methyl;R.sup.2 and R.sup.3 are taken together to form a spirocyclic (C.sub.3 -C.sub.14) carbocyclic ring substituted with 0 to 3 R.sup.13 ; orR.sup.2 or R.sup.3 is taken together with R.sup.4 and the carbon and nitrogen atoms to which they are respectively attached to form a heteroaryl or heterocyclyl group as defined herein, substituted with 0 to 3 R.sup.12 ;R.sup.5 is hydrogen; (C.sub.1 -C.sub.1) alkyl; (C.sub.3 -C.sub.6) cycloalkyl; or aryl;R.sup.6 is hydrogen; (C.sub.1 -C.sub.1) alkyl; (CH.sub.2).sub.r --(C.sub.3 -C.sub.6)cycloalkyl; or (CH.sub.2).sub.s -aryl; where:r and s are each independently an integer selected from 0, 1, and 2;R.sup.8 and R.sup.9 are each independently selected from the group consisting of hydrogen; (C.sub.1 -C.sub.1) alkyl substituted with 0 to 3 R.sup.10 ; a (C.sub.3 -C.sub.14) carbocyclic ring system substituted with 0 to 3 R.sup.12 ; aryl substituted with 0 to 3 R.sup.12 ; and aryl-(C.sub.1 -C.sub.1) alkyl wherein said aryl and alkyl are substituted with 0 to 3 R.sup.12 ; heterocyclyl as defined herein, substituted with 0 to 3 R.sup.12 ; and heterocyclyl-(C.sub.1 -C.sub.4) alkyl as defined herein, wherein said heterocyclyl and alkyl are substituted with 0 to 3 R.sup.12 ;R.sup.10 is independently selected from the group consisting of F; Cl; --C(.dbd.O)OR.sup.14 ; --OH; nitro; cyano; amino; di(C.sub.1 -C.sub.1) alkylamino; (C.sub.1 -C.sub.1) alkyl; (C.sub.1 -C.sub.4) alkoxy; (C.sub.1 -C.sub.4) alkylthio; and (C.sub.1 -C.sub.1) alkyl and (C.sub.1 -C.sub.1) alkoxy each substituted with 1 to 3 substituents independently selected from F and Cl;R.sup.12 when a substituent on a carbon atom, is independently selected from the group consisting of F; Cl; (C.sub.1 -C.sub.1) alkyl; (C.sub.3 -C.sub.6) cycloalkyl; (C.sub.1 -C.sub.4) alkoxy; --C(.dbd.O)OR.sup.14 ; --OH; (C.sub.1 -C.sub.1) alkyl and (C.sub.1 -C.sub.1) alkoxy each substituted with 1 to 3 substituents independently selected from F and Cl; orR.sup.12 when R.sup.12 is attached to a saturated carbon atom, may be .dbd.O or .dbd.S; or when R.sup.12 is attached to a sulfur atom, may be .dbd.O;R.sup.12 when a substituent on a nitrogen atom, is independently selected from the group consisting of hydroxy; hydroxy(C.sub.1 -C.sub.1) alkyl; (C.sub.1 -C.sub.1) alkoxy; (C.sub.3 -C.sub.6) cycloalkyl; (C.sub.1 -C.sub.4) alkylcarbonyl; and phenylR.sup.13 is (C.sub.1 -C.sub.1) alkoxy; andR.sup.14 is hydrogen; hydroxy; (C.sub.1 -C.sub.1) alkyl; (C.sub.3 -C.sub.6) cycloalkyl; or aryl.