Cyclical tripeptide mimetics

(19S,22R)-22-Amino-3,12,21-trioxo-2,6,9,13,20-pentaazatetracyclo[22.2.2.2(6,9).2(14,17)]dotriaconta-1(26),14,16,24,27,29-hexaene-19-carbaldehyde derivatives (I) excluding (19S,22R)-N-[(4-carbamimidoylphenyl)methyl]-22-methanesulfonamido-3,12,21-trioxo-2,6,9,13,20-pentaazatetracyclo[22.2.2.2(6,9).2(14,17)]dotriaconta-1(26),14,16,24,27,29-hexaene-19-carboxamide derivatives (III), are new. (19S,22R)-22-Amino-3,12,21-trioxo-2,6,9,13,20-pentaazatetracyclo[22.2.2.2(6,9).2(14,17)]dotriaconta-1(26),14,16,24,27,29-hexaene-19-carbaldehyde derivatives of formula (I) and their salts and prodrugs, excluding (19S,22R)-N-[(4-carbamimidoylphenyl)methyl]-22-methanesulfonamido-3,12,21-trioxo-2,6,9,13,20-pentaazatetracyclo[22.2.2.2(6,9).2(14,17)]dotriaconta-1(26),14,16,24,27,29-hexaene-19-carboxamide derivatives of formula (III), are new. n : 1 or 2; m : 0-2; R1 : H or up to 3C alkyl (optionally branched); R2 : up to 5C alkyl (optionally branched), up to 7C aryl, up to 7C aralkyl or H; P1 : substituted benzylamino moieties of formula (IIa), substituted pyridin-3-yl-methylamino moieties of formula (IIb), substituted pyridin-2-yl-methylamino moieties of formula (IIc), 4-(aminomethyl)benzylamino, substituted thiophen-2-yl-methylamino moieties of formula (IId), substituted thiazol-2-yl-methylamino moieties of formula (IIe), substituted thiazol-5-yl-methylamino moieties of formula (IIf), (4-amino-cyclohexylmethyl)-amino, -NH-CH 2-(CH 2) x-CH 2-NH-C(=NH 2)-NH 2or -NH-CH 2-(CH 2) x-CH 2-CH 2-NH 2; R3 : H, OH, O-CH 3, NH 2, O-CO-CH 3or CO-O-(CH 2) z-CH 3; z : 1-5; x : 1-3; P4 : H, SO 2-R4, SO 2-NH 2, SO 2-NH-R4, SO 2-N(R4) 2, CO-O-R4, CO-R4, CH 2-COOH or CH 2-COO-C 2H 5; and R4 : 1-10C alkyl (optionally branched or cyclic), 6-10C aryl or 6-10C (hetero)aralkyl (contains 1-3 N, S or O) (all optionally substituted by 1-2 aminomethylene, CN, CF 3, tetrazole, F, Cl, Br, COOH, COOC 2H 5, COOCH 3, OCH 3, ethoxy, isopropoxy, CH 3, ethyl or isopropyl). [Image] [Image] [Image] [Image] ACTIVITY : Hemostatic; Cytostatic; Antiarthritic; Ophthalmological. MECHANISM OF ACTION : Plasmin inhibitor. The plasmin inhibiting effect of (I) was tested in human plasmin using enzyme kinetic assay. The results showed that (19S,22R)-N-[(4-carbamimidoylphenyl)methyl]-22-[(cyclohexylsulfamoyl)amino]-3,12,21-trioxo-2,6,9,13,20-pentaazatetracyclo[22.2.2.26,9.214,17]dotriaconta-1(26),14,16,24,27,29-hexaene-19-carboxamide exhibited inhibition constant (K i) of less than 15 nm. Die Erfindung betrifft Peptidmimetika