Patent ID: 6218415
Filing Date: 2001-04-17
Classification: A61P,C07D

Abstract:
A compound of the formula I ##STR116##in which:W is R.sup.1 -A-B-D-C(R.sup.16) or R.sup.1 -A-B-D-C(R.sup.16).dbd.C;Y is C.dbd.O or C.dbd.S;Z is N(R.sup.0);A is a direct linkage, (C.sub.1 -C.sub.8)-alkanediyl, --NR.sup.2 --N.dbd.CR.sup.2 --, --NR.sup.2 --C(O)--NR.sup.2 --, --NR.sup.2 --C(O)O--, --NR.sup.2 --C(O)S--, --NR.sup.2 --C(S)--NR.sup.2 --, --NR.sup.2 --C(S)--O--, --NR.sup.2 --C(S)--S--, --NR.sup.2 --S(O).sub.n --NR.sup.2 --, --NR.sup.2 --S(O).sub.n --, --NR.sup.2 --S(O).sub.n --, (C.sub.3 -C.sub.12)-cycloalkanediyl, --C.tbd.--C--, --NR.sup.2 --C(O)--, --C(O)--NR.sup.2 --, --(C.sub.5 -C.sub.14)-arylene-C(O)--NR.sup.2 --, --O--, --S(O).sub.n --, (C.sub.5 -C.sub.14)-arylene-, --CO--, (C.sub.5 -C.sub.14)-arylene-CO--, --NR.sup.2 --, --SO.sub.2 --NR.sup.2, --C(O)O--, --O--C(O)--, --N.dbd.CR.sup.2 --, --R.sup.2 C.dbd.N--, --CR.sup.2.dbd.CR.sup.3 -- or --(C.sub.5 -C.sub.14)-arylene-S(O).sub.n --, which in each case may be substituted by NR.sup.2 and/or substituted, once or twice, by (C.sub.1 -C.sub.8)-alkanediyl;B is a direct linkage, (C.sub.1 -C.sub.8)-alkanediyl, (C.sub.5 -C.sub.10)-arylene, (C.sub.3 -C.sub.8)-cycloalkanediyl, --C.tbd.C--, --NR.sup.2 --, --C(O)--, NR.sup.2 --C(O)--, --C(O)--NR.sup.2 --, --NR.sup.2 --C(O)--NR.sup.2, --NR.sup.2 --C(S)--NR.sup.2 --, --OC(O)--, --C(O)O--, --S(O)--, --S(O).sub.2 --, --S(O)--NR.sup.2 --, --S(O).sub.2 --NR.sup.2 --, --NR.sup.2 --S(O)--, --NR.sup.2 --S(O).sub.2 --, --O--, --S-- or --CR.sup.2.dbd.CR.sup.3 --, which in each case may be substituted once or twice by (C.sub.1 -C.sub.6)-alkanediyl, or is a divalent group of a 5- or 6-membered saturated or unsaturated ring which contains 1 or 2 nitrogen atoms and may be substituted, once or twice, by (C.sub.1 -C.sub.6)-alkyl or doubly bonded oxygen or sulfur;D is a direct linkage, (C.sub.1 -C.sub.8)-alkanediyl, (C.sub.5 -C.sub.10)-arylene, --O--, --NR.sup.2 --, --CO--NR.sup.2 --, --NR.sup.2 --CO--, --NR.sup.2 --C(O)--NR.sup.2 --, --NR.sup.2 --C(S)--NR.sup.2 --, --OC(O)--, --C(O)O--, --CO--, --CS--, --S(O)--, --S(O).sub.2 --, --S(O).sub.2 --NR.sup.2 --, --NR.sup.2 --S(O)--, --NR.sup.2 --S(O).sub.2 --, --S--, --CR.sup.2.dbd.CR.sup.3 --, --C.tbd.C--, --NR.sup.2 --N.dbd.CR.sup.2 --, --N.dbd.CR.sup.2, --R.sup.2 C.dbd.N-- or --CH(OH)--, which in each case may be substituted, once or twice, by (C.sub.1 -C.sub.8)-alkanediyl, --CR.sup.2.dbd.CR.sup.3 -- or (C.sub.5 -C.sub.6)-arylene;E is a direct linkage, (C.sub.1 -C.sub.6)-alkanediyl, or (C.sub.2 -C.sub.6)-alkenediyl;F is --CO--NR.sup.2 --;G is ##STR117##R.sup.0 is H, (C.sub.1 -C.sub.8)-alkyl which is optionally substituted, once or more than once, by fluorine, (C.sub.3 -C.sub.12)-cycloalkyl, (C.sub.3 -C.sub.12)-cycloalkyl-(C.sub.1 -C.sub.8)-alkyl, (C.sub.5 -C.sub.14)-aryl, (C.sub.5 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkyl or (C.sub.1 -C.sub.8)-alkyl-C(O)--, (C.sub.3 -C.sub.12)-cycloalkyl-C(O), (C.sub.3 -C.sub.12)-cycloalkyl-(C.sub.1 -C.sub.6)-alkyl-C(O), (C.sub.5 -C.sub.14)-aryl-C(O)-- or (C.sub.5 -C.sub.14)-aryl-(C.sub.1 -C.sub.6)-alkyl-C(O), wherein the alkyl groups optionally are substituted, once or more than once, by fluorine;R.sup.1 is R.sup.2 --C(.dbd.NR.sup.2)NR.sup.2 --, R.sup.2 R.sup.3 N--C(.dbd.NR.sup.2)--, R.sup.2 R.sup.3 N--C--(.dbd.NR.sup.2)--NR.sup.2, or a 4 to 14-membered, monocyclic or polycyclic, aromatic or non-aromatic ring system which may optionally contain 1-4 heteroatoms from the group N, O and S and may optionally be substituted, once or more than once, by substituents from the group R.sup.12, R.sup.13, R.sup.14 and R.sup.15 ;R.sup.2 and R.sup.3 are, independently of each other, H, (C.sub.1 -C.sub.10)-alkyl, which is optionally substituted, once or more than once, by fluorine, (C.sub.3 -C.sub.12)-cycloalkyl, (C.sub.3 -C.sub.12)-cycloalkyl-(C.sub.1 -C.sub.8)-alkyl, (C.sub.5 -C.sub.14)-aryl, (C.sub.5 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkyl, H.sub.2 N, R.sup.8 ONR.sup.9, R.sup.8 OR.sup.9, R.sup.8 OC(O)R.sup.9, R.sup.8 -(C.sub.5 -C.sub.14)-aryl-R.sup.9, R.sup.8 R.sup.8 NR.sup.9, HO-(C.sub.1 -C.sub.8)-alkyl-NR.sup.8 R.sup.9, R.sup.8 R.sup.8 NC(O)R.sup.9, R.sup.8 C(O)NR.sup.8 R.sup.9, R.sup.8 C(O)R.sup.9, R.sup.8 R.sup.8 N--C(.dbd.NR.sup.8)--, R.sup.8 R.sup.8 N--C(.dbd.NR.sup.8)--NR.sup.8 -- or (C.sub.1 -C.sub.18)-alkylcarbonyloxy-(C.sub.1 -C.sub.6)-alkoxycarbonyl;R.sup.4 , R.sup.5, R.sup.6 and R.sup.7 are, independently of each other, H, fluorine, OH, (C.sub.1 -C.sub.8)-alkyl, (C.sub.3 -C.sub.12)-cycloalkyl, (C.sub.3 -C.sub.12)-cycloalkyl-(C.sub.1 -C.sub.8)-alkyl, or R.sup.8 OR.sup.9, R.sup.8 SR.sup.9, R.sup.8 CO.sub.2 R.sup.9, R.sup.8 OC(O)R.sup.9, R.sup.8 -(C.sub.5 -C.sub.14)-aryl-R.sup.9, R.sup.8 N(R.sup.2)R.sup.9, R.sup.8 R.sup.8 NR.sup.9, R.sup.8 N(R.sup.2)C(O)OR.sup.9, R.sup.8 S(O).sub.n N(R.sup.2)R.sup.9, R.sup.8 OC(O)N(R.sup.2)R.sup.9, R.sup.8 C(O)N(R)R.sup.9, R.sup.8 N(R.sup.2)C(O)N(R.sup.2)R.sup.9, R.sup.8 N(R.sup.2)S(O).sub.n (R.sup.2)R.sup.9, R.sup.8 S(O).sub.n R.sup.9, R.sup.8 SC(O)N(R.sup.2)R.sup.9, R.sup.8 C(O)R.sup.9, R.sup.8 N(R.sup.2)C(O)R.sup.9 or R.sup.8 N(R.sup.2)S(O).sub.n R.sup.9 ;R.sup.8 is H, (C.sub.1 -C.sub.8)-alkyl, (C.sub.3 -C.sub.12)-cycloalkyl, (C.sub.3 -C.sub.12)-cycloalkyl-(C.sub.1 -C.sub.8)-alkyl, (C.sub.5 -C.sub.14)-aryl or (C.sub.5 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkyl, wherein the alkyl groups optionally are substituted, once or more than once, by fluorine;R.sup.9 is a direct linkage or (C.sub.1 -C.sub.8)-alkanediyl;R.sup.10 is C(O)R.sup.11, C(S)R.sup.11, S(O).sub.n R.sup.11, P(O).sub.n R.sup.11 or a four- to eight-membered, saturated or unsaturated heterocycle which contains 1, 2, 3 or 4 heteroatoms from the group N, O and S;R.sup.11 is OH, (C.sub.1 -C.sub.8)-alkoxy, (C.sub.5 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkoxy, (C.sub.5 -C.sub.14)-aryloxy, (C.sub.1 -C.sub.8)-alkylcarbonyloxy-(C.sub.1 -C.sub.4)-alkoxy, (C.sub.5 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkylcarbonyloxy-(C.sub.1 -C.sub.6)-alkoxy, NH.sub.2, mono- or di(C.sub.1 -C.sub.8 -alkyl)amino, (C.sub.5 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkylamino, (C.sub.1 -C.sub.8)-dialkylaminocarbonylmethyloxy, (C.sub.5 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-dialkylaminocarbonylmethyloxy or (C.sub.5 -C.sub.14)-arylamino or an L- or D-amino acid;R.sup.12, R.sup.13, R.sup.14 and R.sup.15 are, independently of each other, H, (C.sub.1 -C.sub.10)-alkyl which is optionally substituted, once or more than once, by fluorine, (C.sub.3 -C.sub.12)-cycloalkyl, (C.sub.3 -C.sub.12)-cycloalkyl-(C.sub.1 -C.sub.8)-alkyl, (C.sub.5 -C.sub.14)-aryl, (C.sub.5 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkyl, H.sub.2 N, R.sup.8 ONR.sup.9, R.sup.8 OR.sup.9, R.sup.8 OC(O)R.sup.9, R.sup.8 R.sup.8 NR.sup.9, R.sup.8 (C.sub.5 -C.sub.14)-aryl-R.sup.9, HO-(C.sub.1 -C.sub.8)-alkyl-N(R.sup.2)R.sup.9, R.sup.8 N(R.sup.2)C(O)R.sup.9, R.sup.8 C(O)N(R.sup.2)R.sup.9, R.sup.8 C(O)R.sup.9, R.sup.2 R.sup.3 N--C(.dbd.NR.sup.2)--NR.sup.2 --, R.sup.2 R.sup.3 N--C(.dbd.NR.sup.2), .dbd.O or .dbd.S; wherein optionally two adjacent substituents from the group R.sup.12 to R.sup.15 are also together --OCH.sub.2 O--, --OCH.sub.2 CH.sub.2 O-- or --OC(CH.sub.3).sub.2 O--;R.sup.16 is H, (C.sub.1 -C.sub.10)-alkyl which is optionally substituted, once or more than once, by fluorine, (C.sub.3 -C.sub.12)-cycloalkyl, (C.sub.3 -C.sub.12)-cycloalkyl-(C.sub.1 -C.sub.8)-alkyl, (C.sub.5 -C.sub.14)-aryl, (C.sub.5 -C.sub.14)-aryl-(C.sub.1 -C.sub.8)-alkyl, (C.sub.2 -C.sub.20)-alkenyl or (C.sub.2 -C.sub.10)-alkynyl;n is 1 or 2;p and q are, independently of each other, 0 or 1;and the physiologically tolerated salts thereof,with compounds being excluded wherein the group R.sup.1 -A-B-D-C-(R.sup.16) representing W is R.sup.1 --K--C(R.sup.16) and wherein the group R.sup.1 -A-B-D-C(R.sup.16).dbd.C representing W is R.sup.1 --K--CH.dbd.C (R.sup.16.dbd.H), and wherein in the groups R.sup.1 --K--C(R.sup.16) and R.sup.1 --K--CH.dbd.C,R.sup.1 is X--NH--C(.dbd.NH)--(CH.sub.2).sub.p, X.sup.1 --NH--(CH.sub.2).sub.p or 4-imidazolyl-CH.sub.2 --, wherein p is an integer from 0 to 3,X is hydrogen, (C.sub.1 -C.sub.6)-alkyl, (C.sub.1 -C.sub.6)-alkylcarbonyl, (C.sub.1 -C.sub.6)-alkoxycarbonyl, (C.sub.1 -C.sub.18)-alkylcarbonyloxy-(C.sub.1 -C.sub.6)-alkoxycarbonyl, (C.sub.6 -C.sub.14)-arylcarbonyl, (C.sub.6 -C.sub.14)-aryloxycarbonyl, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.6)-alkoxycarbonyl, hydroxyl, (C.sub.1 -C.sub.6)-alkoxy, (C.sub.6 -C.sub.14)-aryl-(C.sub.1 -C.sub.6)-alkoxy or amino, with the aryl groups in X being pure carbocycles which are optionally substituted once or more than once.X.sup.1 is (C.sub.4 -C.sub.14)-arylcarbonyl, (C.sub.4 -C.sub.14)-aryloxycarbonyl, (C.sub.4 -C.sub.14)-aryl-(C.sub.1 -C.sub.6)-alkoxycarbonyl, (C.sub.4 -C.sub.14)-aryl-(C.sub.1 -C.sub.6)-alkoxy or R'--NH--C(.dbd.N--R""), where R' and R"" have, independently of each other, the meanings of X and where the aryl groups in X.sup.1 are pure carbocycles which are optionally substituted once or more than once.K is (C.sub.1 -C.sub.6)-alkanediyl, (C.sub.3 -C.sub.7)-cycloalkanediyl, phenylene, phenylene-(C.sub.1 -C.sub.6)-alkanediyl, (C.sub.1 -C.sub.6)-alkanediylphenylene, phenylene-(C.sub.2 -C.sub.6)-alkenediyl or a divalent group of a 5- or 6-membered, saturated or unsaturated ring which contains 1 or 2 nitrogen atoms and may be substituted, once or twice, by (C.sub.1 -C.sub.6)-alkyl or doubly bonded oxygen or sulfur.