Vitronectin receptor antagonists, their preparation and their use

A compound of formula I

• A—B—D—E—F—G (I)
• in which:
• A1=A1 or A2, where
• A1=R2R3N—C(═NR2)NR2C(O)—, R2R3N—C(═NR2)NR2C(DS)—, R2R3N—C(═NR2)NR2—S(O)n—,
• where, in A1 or A2
• is a 5-membered to 10-membered monocyclic or polycyclic, aromatic, or nonaromatic ring system which contains the grouping
• and, in addition, can contain from 1 to 4 heteroatoms selected from the group consisting of N, O, and S, and, optionally, can be substituted at least once by R12, R13, R14 or R15;
• B is a direct linkage, (C1-C8)-alkanediyl, —CR2═CR3—, (C5-C10)-arylene, (C3-C8)-cycloalkylene, or —C≡C—, which can in each case be substituted, once or twice, by (C1-C8)-alkyl;
• D is a direct linkage, (C1-C8)-alkanediyl, (C5-C10)-arylene, —O—, —NR2—, —CO—NR2—, —NR2—CO—, —NR2—C(O)—NR2—, —NR2—C(S)—NR2—, —OC(O)—, —C(O)O—, —CO—, —CS—, —S(O)—, —S(O)2—, —S(O)2—NR2—, —S(O)—NR2—, —NR2—S(O)—, —NR2—S(O)2—, —S—, —CR2═CR3, —C≡C—, —NR2—N═CR2—, —N═CR2, —R2C═N—, or —CH(OH)—, which can in each case be substituted, once or twice, by (C1-C8)-alkyl, —CR2═CR2—, or (C5-C6)-aryl, where if B is a direct linkage, then D can also be a direct linkage or a radical as defined under D, which radical is substituted once or twice, as described under D, and is linked to B by way of one of these substituents;
• E is selected from the group consisting of
• R1b and R2b are, independent of each other, from one to three groups selected from the group consisting of hydrogen, halogen, cyano, carboxamido, carbamoyloxy, formyloxy, formyl, azido, nitro, ureido, thioureido, hydroxyl, mercapto, sulfonamido, and an optionally substituted radical selected from the group consisting of C1-C12-alkyl, C2-C12-alkenyl, C3-C12-alkynyl, C3-C12-cycloalkyl, C6-C14-aryl, C6-C10-aryl-C1-C9-alkyl, C1-C12-alkyloxy, C6-C14-aryloxy, and C1-C12-acylamino, where the substituents are a radical selected from the group consisting of halogen, cyano, azido, nitro, hydroxyl, mercapto, sulfonamido, ureido, thioureido, carboxamido, carbamoyloxy, formyloxy, formyl, C1-C4 alkoxy, phenyl, and phenoxy;
• and
• R25b and R26b are, independent of each other, hydrogen, C1-C10-alkyl, C3-C10-alkenyl, C6-C14-aryl, or C1-C6-alkyl-C6-C10-aryl, or
• R25b and R26b together form a trimethylene, tetramethylene, pentamethylene, or 3-oxopentamethylene radical;
• F is defined like D;
• and
• where
• R2 and R3 are, independent of each other, hydrogen, (C1-C10)-alkyl, which is optionally substituted at least once by fluorine, (C3-C12)-cycloalkyl, (C3-C12)-cycloalkyl-(C1-C8)-alkyl, (C5-C14)-aryl, (C5-C14)-aryl-(C1-C8)-alkyl, R8OC(O)R9, R8R8NC(O)R9, or R8C(O)R9;
• R4, R5, R6, and R7 are, independent of each other, hydrogen, fluorine, OH, (C1-C8)-alkyl, (C3-C14)-cycloalkyl, (C3-C14)-cycloalkyl-(C1-C8)-alkyl, or R8OR9, R8SR9, R8CO2R9, R8OC(O)R9, R8—(C5-C14)-aryl-R9, R8N(R2)R9, R8R8NR9, R8N(R2)C(O)OR9, R8S(O)nN(R2)R9, R8OC(O)N(R2)R9, R8C(O)N(R2)R9, R8N(R2)C(O)N(R2)R9, R8N(R2)S(O)nN(R2)R9, R8S(O)nR9, R8SC(O)N(R2)R9, R8C(O)R9, R8N(R2)C(O)R9, or R8N(R2)S(O)nR9;
• R8 is hydrogen, (C1-C8)-alkyl, (C3-C14)-cycloalkyl, (C3-C14)-cycloalkyl-(C1-C8)-alkyl, (C5-C14)-aryl or (C5-C14)-aryl-(C1-C8)-alkyl, where the alkyl radicals can be substituted once or more than once by fluorine;
• R9 is a direct linkage or (C1-C8)-alkanediyl;
• R10 is C(O)R11, C(S)R11, S(O)nR11, P(O)(R11)2, or a four-membered to eight-membered, saturated or unsaturated heterocycle which contains 1, 2, 3, or 4 heteroatoms selected from the group consisting of N, O, and S;
• R11 is OH, (C1-C8)-alkoxy, (C5-C14)-aryl-(C1-C8)-alkoxy, (C5-C14)-aryloxy, (C1-C8)-alkylcarbonyloxy-(C1-C4)-alkoxy, (C5-C14)-aryl-(C1-C8)-alkylcarbonyloxy-(C1-C6)-alkoxy, NH2, mono- or di-((C1-C8)-alkyl)-amino, (C5-C14)-aryl-(C1-C8)-alkylamino, (C1-C8)-dialkylaminocarbonylmethyloxy, (C5-C14)-aryl-(C1-C8)-dialkylaminocarbonylmethyloxy, (C5-C14)-arylamino, or the radical of an L-amino acid or D-amino acid;
• R12, R13, R14, and R15 are, independent of each other, hydrogen, (C1-C10)-alkyl which is optionally substituted once or more than once by fluorine, (C3-C12)-cycloalkyl, (C3-C12)-cycloalkyl-(C1-C8)-alkyl, (C5-C14)-aryl, (C5-C14)-aryl-(C1-C8)-alkyl, H2N, R8ONR9, R8OR9, R8OC(O)R9, R8R8NR9, R8—(C5-C14)-aryl-R9, HO—(C1-C8)-alkyl-N(R2)R9, R8N(R2)C(O)R9, R8C(O)N(R2)R9, R8C(O)R9, R2R3N—C(═NR2)—NR2, R2R3N—C(═NR2), ═O, or ═S;
• where two adjacent substituents from R12, R13, R14, and R15 can also together be —OCH2O—, —OCH2CH2O—, or —OC(CH3)O—;
• n is 1 or 2;
• p and q are, independently of each other, 0 or 1;
• in all its stereoisomeric forms and mixtures thereof in all proportions, and its physiologically tolerated salts.