ANTAGONISTS OF VITRONECTIN RECEPTORS, PROCESS OF THEIR PREPARATION AND USE

摘要

Guanidine and cycloguanidine derivatives of formula A-B-D-E-F-G (I) and their salts are new. A = R<2>R<3>N-C(=NR<2>)NR<2>Z- or a group of formula (a) or (b); Z = C(Q) or S(O)n; Q = O or S; n = 1 or 2; R = 5-10 membered mono- or polycyclic, aromatic or non-aromatic ring (optionally containing 1-4 N, O and/or S and optionally substituted by 1 or more of R<12>-R<15>); B = direct bond; or alkyl, -CR<2>=CR<3>-, 5-10C aryl, 3-8C cycloalkyl or -C IDENTICAL C- (all optionally mono- or disubstituted by 1-8C alkyl), e.g. Me-Ph-Me or Et-CH=CH-; D, F = direct bond or alkyl, 5-10C aryl, -Q-; -NR<2>-, -CO-NR<2>-, -NR<2>-CO-, -NR<2>-C(Q)-NR<2>-, -O-C(O)-,-C(O)-O-, -C(Q)-, -S(O)n, -S(O)n-NR<2>, -NR<2>-S(O)n, -CR<2>=CR<3>-, -C IDENTICAL C-, -NR<2>-N=CR<2>-, -N=CR<2>-, -R<2>C=N- or -CH(OH)- (all optionally mono- or disubstituted by alkyl, -CR<2>-CR<2>- or 5-6C aryl), e.g. Me-Ph-CH=CH- or Et-O-, and D is optionally linked to B via one of these substituents; E = template of a fibrinogen receptor antagonist; G = -CR<4>R<5>-(CR<6>R<7>)p-(CH2)p-R<10>; R<2>, R<3> = H; 1-10C alkyl (optionally substituted by 1 or more F); cycloalkyl; cycloalkyl-alkyl; aryl; aryl-alkyl; R<8>OC(O)R<9>; R<8>R<8>NC(O)R<9>; or R<6>C(O)R<9>; R<4>-R<7> = H; F; OH; alkyl; cycloalkyl; cycloalkyl-alkyl; R<8>QR<9>; R<8>CO2R<9>; R<8>OC(O)R<9>; R<8>-5-14C aryl-R<9>; R<8>N(R<2>)R<9>; R<8>R<8>NR<9>; R<8>N(R<2>)CO(O)R<9>; R<8>S(O)n-N(R<2>)R<9>; R<8>QC(O)N(R<2>)R<9>; R<8>C(O)N(R<2>)R<9>; R<8>N(R<2>)C(O)N(R<2>)R<9>; R<8>N(R<2>)S(O)N(R<2>)R<9>; R<8>S(O)nR<9>; R<8>C(O)R<9>; R<8>N(R<2>)C(O)R<9>; or R<8>N(R<2>)S(O)nR<9>; R<8> = H; Alk; cycloalkyl; cycloalkyl-Alk; aryl; or aryl-Alk; Alk = alkyl (optionally substituted by 1 or more F); R<9> = direct bond or alkyl; R<10> = C(Q)R<11>; S(O)n-NR<11>; P(O)nR<11>; or a 4-8 membered saturated or unsaturated heterocycle containing 1-4 N, O and/or S, e.g. tetrazolyl, imidazolyl, pyrazolyl, oxazolyl or thiadiazolyl; R<11> = OH; alkoxy; aryl-alkoxy; aryloxy; alkylcarbonyloxy-(1-4C) alkoxy; aryl-alkylcarbonyloxy-(1-6C) alkoxy; NH2; NH(alkyl); N(alkyl)2; aryl-alkylamino; dialkylaminocarbonylmethoxy; aryl- dialkylaminocarbonylmethoxy; arylamino; or a L- or D-aminoacid; R<12>-R<15> = H; 1-10C alkyl (optionally substituted by one or more F); 3-12C cycloalkyl; 3-12C cycloalkyl-alkyl; aryl; aryl-alkyl; NH2; R<8>ONR<9>; R<8>OR<9>; R<8>OC(O)R<9>; R<8>R<8>NR<9>; R<8>-aryl-R<9>; HO-alkyl-N(R<2>)R<9>; R<8>N(R<2>)C(O)R<9>; R<8>C(O)N(R<2>)R<9>; R<8>C(O)R<9>; R<2>R<3>N-C(=NR<2>)-NR<2>; R<2>R<3>N-C(=NR<2>); or Q; or two adjacent R<1->R<15> substituents form -O-(CH2)n-O- or -OC(CH3)2O-; p, q = 0 or 1; alkyl moieties have 1-8C, cycloalkyl moieties 3-14C and aryl moieties 5-14C unless specified otherwise; compounds where E is a 6-membered aromatic ring (optionally containing 1-4 N and/or 1-4 substituents ) and the compound 4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine are excluded.