Patent ID: 6274584
Filing Date: 2001-08-14
Classification: A61P,C07C,C07D

Abstract:
A compound of formula I ##STR200##formula IwhereinA is A.sup.1 or A.sup.2 ;G is G.sup.1 or G.sup.2 ;D is hydrogen, --O--(CH.sub.2).sub.k --R.sup.5a, ##STR201##wherein R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 independently are hydrogen, halogen, aryl, C.sub.1-6 alkyl or C.sub.1-6 -alkoxy;R.sup.5a is hydrogen, aryl optionally substituted with halogen or C.sub.1-6 -alkyl, or C.sub.1-6 -alkyl optionally substituted with halogen or C.sub.1-6 -alkyl,k is 0, 1, 2, or 3;E is hydrogen, --O--(CH.sub.2).sub.l --R.sup.10a, ##STR202##wherein R.sup.10, R.sup.11, R.sup.12, R.sup.13 and R.sup.14 independently are hydrogen, halogen, aryl, C.sub.1-6 -alkyl, C.sub.1-6 -alkoxy, --CONR.sup.15 R.sup.16, --(CH.sub.2).sub.v --NR.sup.15 SO.sub.2 R.sup.17, --(CH.sub.2).sub.v --NR.sup.15 COR.sup.16, --(CH.sub.2).sub.v --OR.sup.17, --(CH.sub.2).sub.v --OCOR.sup.16, --CH(R.sup.15)R.sup.16, --(CH.sub.2).sub.v --NR.sup.15 --CS--NR.sup.16 R.sup.18, --(CH.sub.2).sub.v NR.sup.15 --CO--NR.sup.16 R.sup.18, ##STR203##whereinX.sup.1 is --N(R.sup.19)--, --O-- or --S--,X.sup.2 is --C(R.sup.2).dbd. or --N.dbd.,X.sup.3 is --C(R.sup.21).dbd. or --N.dbd.,X.sup.4 is --C(R.sup.22).dbd. or --N.dbd.;R.sup.19 is hydrogen or C.sub.1-6 -alkyl optionally substituted with aryl,R.sup.20, R.sup.21 and R.sup.22 independently are hydrogen, --COOR.sup.23, --CONR.sup.24 R.sup.25, --(CH.sub.2).sub.w NR.sup.24 R.sup.25, --(CH.sub.2).sub.w OR.sup.23, --(CH.sub.2).sub.w R.sup.23 or halogen;R.sup.15, R.sup.16, R.sup.23, R.sup.24 and R.sup.25 independently are hydrogen or C.sub.1-6 -alkyl optionally substituted with halogen, --N(R.sup.26)R.sup.27, hydroxyl, C.sub.1-6 -alkoxy, C.sub.1-6,alkoxycarbonyl, C.sub.1-6 -calkyl carbonyloxy or aryl,or R.sup.16 is ##STR204##whereinQ.sup.1 is --CH< or --N<,T.sup.1 and J.sup.1 are independently --CH.sub.2 --, --CO--, --O--, --S, --NR-- or a valence bond,where R.sup.28 is hydrogen or linear or branched C.sub.1-6 -alkyl;t and u are independently 0, 1, 2, 3 or 4;R.sup.17 is C.sub.1-6 alkyl or phenyl optionally substituted with hydroxyl or aryl;R.sup.18 is C.sub.1-6 alkyl;R.sup.26 and R.sup.27 are independently hydrogen or C.sub.1-6 -alkyl;v and w are independently 0, 1, 2 or 3;R.sup.10a is hydrogen, aryl optionally substituted with halogen or C.sub.1-6 -alkyl, or C.sub.1-6 -alkyl optionally substituted with halogen or C.sub.1-6 -alkyl,I is 0, 1, 2, or 3;A.sup.1 is ##STR205## or R.sup.33 --NH--(CR.sup.34 R.sup.35).sub.p.(CH.sub.2).sub.m --M--(CHR.sup.36).sub.o --(CH.sub.2).sub.n --wherein R.sup.29, R.sup.30, R.sup.31, R.sup.32, R.sup.33, R.sup.34, R.sup.35 and R.sup.36 are independently hydrogen or C.sub.1-6 -alkyl optionally substituted with halogen, amino, hydroxyl or aryl;R.sup.33 and R.sup.34, R.sup.33 and R.sup.35 or R.sup.34 and R.sup.35 may optionally form --(CH.sub.2).sub.i --Z--(CH.sub.2).sub.j --, wherein i and independently are 1 or 2 and Z is --O--, --S-- or a valence bond;n, m and q are independently 0, 1, 2, or 3;o and p are independently 0 or 1;M is --CR.sup.37.dbd.CR.sup.38 --, --O--, --S-, or a valence bond;R.sup.37 and R.sup.38 are independently hydrogen, or C.sub.1-6 -alkryl optionally substituted with aryl;A.sup.2 is ##STR206## or R.sup.33 --NH--(CR.sup.34 R.sup.35).sub.p.(CH.sub.2).sub.m --M--(CHR.sup.36).sub.o --(CH.sub.2).sub.n --wherein R.sup.29, R.sup.30, R.sup.31, R.sup.32, R.sup.33, R.sup.34, R.sup.35 and R.sup.36 are independently hydrogen or C.sub.1-6 -alkyl optionally substituted with halogen, amino, hydroxyl or aryl;R.sup.33 and R.sup.34, R.sup.33 and R.sup.35 or R.sup.34 and R.sup.35 may optionally form --(CH.sub.2).sub.i --Z--(CH.sub.2).sub.j --, wherein i and independently are 1 or 2 and Z is --O--, --S-- or a valence bond;n, m and q are independently 0, 1, 2, or 3;o and p are independently 0 or 1;M is --CR.sup.37.dbd.CR.sup.38 --, --O--, or --S--;R.sup.37 and R.sup.38 are independently hydrogen, or C.sub.1-6 -alkyl optionally substituted with aryl;G.sup.1 is hydrogen, halogen, aryl, C.sub.1-6 -alkyl, C.sub.1-6 -alkoxy, --CONR.sup.39 R.sup.40, --(CH.sub.2).sub.e --NR.sup.39 SO.sub.2 R.sup.41, --(CH.sub.2).sub.e --NR.sup.39 COR.sup.40, --(CH.sub.2).sub.e OR.sup.41, --(CH.sub.2).sub.e --OCOR.sup.40, --CH(R.sup.39)R.sup.40, --CON.sup.39 --NR.sup.40 R.sup.42, --(CH.sub.2).sub.e --NR.sup.39 CS--NR.sup.40 R.sup.42, --(CH.sub.2).sub.e --NR.sup.39 --CO--NR.sup.40 R.sup.42, ##STR207##whereinX.sup.5 is --N(R.sup.43)--, --O-- or --S--,X.sup.6 is --C(R.sup.44).dbd. or --N.dbd.,X.sup.7 is --C(R.sup.45).dbd. or --N.dbd.,X.sup.8 is --C(R.sup.46).dbd. or --N.dbd.,R.sup.43 is hydrogen or C.sub.1-6 -alkyl optionally substituted with aryl,R.sup.44, R.sup.45 and R.sup.46 independently are hydrogen, --COOR.sup.47, --CONR.sup.48 R.sup.49, --(CH.sub.2).sub.f NR.sup.48 R.sup.49, --(CH.sub.2).sub.f OR.sup.47, --(CH.sub.2).sub.f R.sup.47 or halogen;R.sup.39, R.sup.40, R.sup.47, R.sup.48 and R.sup.49 independently are hydrogen or C.sub.1-6 -alkyl optionally substituted with halogen,--N(R.sup.50)R.sup.51, hydroxyl, C.sub.1-6 -alkoxy, C.sub.1-6 -alkoxycarbonyl,C.sub.1-6 -alkylcarbonyloxy or aryl,or R.sup.40 is ##STR208##whereinQ.sup.2 is --CH< or --N<,J.sup.2 and T.sup.2 are independently --CH.sub.2 --, --CO--, --O--, --S--, --NR.sup.52 -- or a valence bond,where R.sup.52 is hydrogen or C.sub.1-6 -alkyl;x and y are independently 0, 1, 2, 3 or 4;R.sup.41 is C.sub.1-6 alkyl substituted with aryl;R.sup.42 is Cl alkyl;R.sup.50 and R.sup.51 are independently hydrogen or C.sub.1-6 -alkyl;e and f are independently 0, 1, 2 or 3;G.sup.2 is hydrogen or C.sub.1-6 -alkyl;R.sup.1 and R.sup.2 are taken together to form a bridge of type ##STR209##wherein R.sup.55 and R.sup.56 independently of each other are hydrogen, C.sub.1-6 -alkyl, optionally substituted with hydroxyl, C.sub.1-6 -alkoxyl or aryl;R.sup.55 and R.sup.56 may be taken together to form .dbd.O or .dbd.S;c and d are independently 0, 1, or 2;c+d is 0, 1, or 2;R.sup.54 is hydrogen or C.sub.1-6 -alkyl,R.sup.3 and R.sup.4 are hydrogen, C.sub.1-6 -alkyl, optionally substituted with hydroxyl, C.sub.1-6 -alkoxyl, halogen, or aryl;R.sup.3 and R.sup.4 may be taken together to form .dbd.S, .dbd.O;L.sup.1 is CR.sup.57 or N;L.sup.2 is CR.sup.58 or N;R.sup.57 and R.sup.58 independently are hydrogen, C.sub.1-6 -alkyl, optionally substituted with hydroxyl, halogen, C.sub.1-6 -alkoxy, or aryl;a and b independently are 0, 1, 2, or 3;with the proviso thatwhen G is G.sup.2 and L.sup.1 is CR.sup.55 and L.sup.2 is CR.sup.56, then A is A.sup.2 ;when either of L.sup.1 or L.sup.2 is N, then G is G.sup.1 and A is A.sup.1 ;or a pharmaceutically acceptable salt thereof.