Patent EA-002921-B1 (EA)
Title: Novel acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists
Inventor: PEYMAN ANUSCHIRWAN
IPC: A61K31/27
Filed: 1998-12-10
Abstract: 1. A compound of the formula I   in which the radicals R<1> and R<2> together are a saturated or unsaturated bivalent (C2-C3)-alkylene radical, R<4> is hydrogen or (C1-C6) alkyl; R<5> is phenyl or benzyl; R<6> is hydrogen; A is CH2 or O; m is 1, 2 or 3; n is 0 or 1;  in all its stereoisomeric forms and mixtures thereof in all ratios, and its physiologically tolerable salts and its prodrugs. 2. A compound of the formula I as claimed in Claim 1, in which  R<5> is benzyl in all its stereoisomeric forms and mixtures thereof in all ratios, and its physiologically tolerable salts and its prodrugs. 3. A compound of the formula I as claimed in any of Claims 1 or 2, in which R<4> is hydrogen or (C1-C4) alkyl; R<5> is benzyl; A is CH2; m is 1; n is 1; in all its stereoisomeric forms and mixtures thereof in all ratios, and its physiologically tolerable salts and its prodrugs. 4. A compound of the formula I as claimed in any of Claims 1 or 2, in which  R<4> is hydrogen or (C1-C4) alkyl; R<5> is benzyl; A is oxygen; m is 1; n is 1; in all its stereoisomeric forms and mixtures thereof in all ratios, and its physiologically tolerable salts and its prodrugs. 5. A compound of the formula I as claimed in any of Claims 1 or 2, in which  R<4> is hydrogen or (C1-C4) alkyl; R<5> is benzyl; A is oxygen; m is 3; n is 0; in all its stereoisomeric forms and mixtures thereof in all ratios, and its physiologically tolerable salts and its prodrugs. 6. A compound of the formula I as claimed in any of Claims 1 or 2, in which  R<4> is hydrogen; R<5> is benzyl; A is oxygen; m is 3; n is 0; in all its stereoisomeric forms and mixtures thereof in all ratios, and its physiologically tolerable salts and its prodrugs. 7. (2S)-Benzyloxycarbonylamino-3-(4-(3-(1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)-propyloxy)phenyl)propionic acid and its physiologically tolerable salts and its prodrugs. 8. (2S)-2-Benzyloxycarbonylamino-3-(4-(2-(1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)-ethyl)benzoylamino)propionic acid and its physiologically tolerable salts and its prodrugs. 9. (2S)-2-Benzyloxycarbonylamino-3-(4-((1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl)-methyloxy)benzoylamino)propionic acid and its physiologically tolerable salts and its prodrugs. 10. (2S)-2-Benzyloxycarbonylamino-3-(4-(3-guanidino-3-oxopropyl)benzoylamino)-propionic acid and its physiologically tolerable salts and its prodrugs. 11. A process for the preparation of compounds of the formula I as claimed in any of Claims 1 to 10, wherein a carboxylic acid or a carboxylic acid derivative of the formula III:   in which R<4>, R<5>, A, n and m are defined as indicated in Claims 1 to 10, or alternatively functional groups can be present in the form of precursors or in protected form, and X is a nucleophilically substitutable leaving group, is reacted with a guanidine or guanidine derivative of the formula IV:   in which R<1>, R<2> and R<6> are defined as indicated in Claims 1 to 10, or alternatively functional groups can be present in the form of precursors or in protected form. 12. A pharmaceutical preparation, comprising at least one compound of the formula I as claimed in any of Claims 1 to 10 and/or its physiologically tolerable salt and/or its prodrug together with a pharmaceutically innocuous carrier. 13. Use of a compound of the formula I as claimed in any of Claims 1 to 10 and/or its physiologically tolerable salt and/or its prodrug as a pharmaceutical preparation. 14. Use of a compound of the formula I as claimed in any of Claims 1 to 10 and/or its physiologically tolerable salt and/or its prodrug as a victronectin receptor antagonist. 15. Use of a compound of the formula I as claimed in any of Claims 1 to 10 and/or its physiologically tolerable salt and/or its prodrug as inhibitor of bone resorption or for the therapy or prophylaxis of osteoporosis. 16. Use of a compound of the formula I as claimed in any of Claims 1 to 10 and/or its physiologically tolerable salt and/or its prodrug as inhibitor of tumor growth or tumor metastasis. 17. Use of a compound of the formula I as claimed in any of Claims 1 to 10 and/or its physiologically tolerable salt and/or its prodrug as antiinflammatory or for the therapy or prophylaxis of cardiovascular disorders, restenosis, arteriosclerosis, nephropathies or retinopathies.