Patent EA-004369-B1 (EA)
Title: Naphthyridine derivatives, process or their preparation, their use and pharmaceutical compositions comprising them
Inventor: PEYMAN ANUSCHIRVAN
IPC: A61P19/02
Filed: 2000-06-26
Abstract: 1. A compound of the formula I, in which G is a residue of the formula II -(CR<1>R<2>)n-A-(CR<1>R<2>)m-(CR<1>R<3>)i-(CR<1>R<2>)q-R<4> II A is a direct bond; B is (C1-C6) or hydroxy, where all B groups are independent of one another and can be identical or different; X is hydrogen; Y is hydrogen; Z is N; R<1> and R<2> are hydrogen, (C1-C4)-alkyl, R<6>S(O)2NHR<7> or R<6>OC(O)NHR<7>, in which all R<1> and R<2> groups are independent of one another and can be identical or different; R<3> is hydrogen, (C1-C12)-alkyl, (C3-C14)-cycloalkyl, (C3-C14)-cycloalkyl-(C1-C6)-alkyl-, (C5-C14)-aryl, (C5-C14)-aryl-(C1-C6)-alkyl, (C5-C14)-heteroaryl, (C5-C14)-heteroaryl-(C1-C6)-alkyl, R<6>R<6>'N-R<7>, R<6>S(O)2N(R<5>)R<7>, R<6>OC(O)N(R<5>)R<7>, or R<6>C(O)N(R<5>)R<7>, where alkyl can be monounsaturated or poly-unsaturated and where alkyl, cycloalkyl, aryl, and heteroaryl can be monosubstituted or polysubstituted by R<6>, fluorine, chlorine, bromine, cyano, trifluoromethyl, R<6>C(O) R<7>, or R<6>-O-R<7>; R<4> is-C (O) R<8>; R<5> is hydrogen or (C1-C4)-alkyl; R<6> and R<6'> are hydrogen, (C1-C12)-alkyl, (C3-C14)-cycloalkyl, (C3-C14)-cycloalkyl-(C1-C8)-alkyl-, (C5-C14)-aryl, (C5-C14)-aryl-(C1-C8)-alkyl, (C5-C14)-heteroaryl, or (C5-C14)-heteroaryl-(C1-C8)-alkyl, where aryl, heteroaryl, cycloalkyl and alkyl can be substituted one, two or three times by identical or different substituents from fluorine, chlorine, bromine, cyano, trifluoromethyl, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-alkylamino, di-((C1-C6)-alkyl)amino, (C5-C14)-aryl and (C5-C14)-heteroaryl, and where all R<6> and R<6'> groups are independent of one another and can be identical or different; R<7> is a direct bond; R<8> is hydroxy or -((C1-C4)-alkoxy; n is zero, one or two; m is zero or one; i is zero or one; q is zero, one or two; r is zero, one or two; s is zero, one or two; t is zero; in all their stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts and their prodrugs. 2. A compound of the formula I as claimed in claim 1, in which G is a residue of the formula II -(CR<1>R<2>)n-A-(CR<1>R<2>)m-(CR<1>R<3>)i-(CR<1>R<2>)q-R<4> II A is a direct bond; X is hydrogen; Y is hydrogen; Z is N; R<1> and R<2> are hydrogen or -(C1-C2)-alkyl, in which all R<1> and R<2> groups are independent of one another and can be identical or different; R<3> is R<6>R<6>'N-R<7>, R<6>S(O)2N(R<5>)R<7>, R<6>OC(O)N(R<5>)R<7>, or R<6>C(O)N(R<5>)R<7>R<4>; R<5> is hydrogen or (C1-C4)-alkyl; R<4> is-C(O)R<8>; R5 is hydrogen or (C1-C2)-alkyl; R<6> and R<6'> are hydrogen, (C1-C12)-alkyl, (C3-C14)-cycloalkyl, (C3-C14)-cycloalkyl-(C1-C8)-alkyl-, (C5-C14)-aryl, (C5-C14)-aryl-(C1-C8)-alkyl, (C5-C14)-heteroaryl, or (C5-C14)-heteroaryl-(C1-C8)-alkyl, where aryl, heteroaryl, cycloalkyl and alkyl can be substituted one, two or three times by identical or different substituents from fluorine, chlorine, bromine, cyano, trifluoromethyl, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-alkylamino, di-((C1-C6)-alkyl)amino, (C5-C14)-aryl and (C5-C14)-heteroaryl, and where all R<6> and R<6'> groups are independent of one another and can be identical or different; R<7> is a direct bond; R<8> is hydroxy or -((C1-C4)-alkoxy; n is zero, one or two; m is zero or one; i is zero or one; q is zero, one or two; r is zero; s is zero; t is zero; in all their stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts and their prodrugs. 3. A compound of the formula I as claimed in claims 1 or 2, in which G is a residue of the formula II -(CR<1>R<2>)n-A-(CR<2>R<2>)m-(CR<1>R<3>)i-(CR<1>R<2>)q-R<4> II A is a direct bond; X is hydrogen; Y is hydrogen; Z is N; R<1> and R<2> are hydrogen; R<3> is R<6>S(O)2N(R<5>)R<7> or R<6>OC(O)N(R<5>)R<7>; or R<6>C(O)N(R<5>)R<7>R<4> is-C (O) R<8>; R<5> is hydrogen or (C1-C4)-alkyl; R<4> is-C(O)R<8>; R5 is hydrogen; R<6> is hydrogen, (C1-C12)-alkyl, (C3-C14)-cycloalkyl, (C3-C14)-cycloalkyl-(C1-C8)-alkyl-, (C5-C14)-aryl, (C5-C14)-aryl-(C1-C8)-alkyl, (C5-C14)-heteroaryl, or (C5-C14)-heteroaryl-(C1-C8)-alkyl, where aryl, heteroaryl, cycloalkyl and alkyl can be substituted one, two or three times by identical or different substituents from fluorine, chlorine, bromine, cyano, trifluoromethyl, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-alkylamino, di-((C1-C6)-alkyl)amino, (C5-C14)-aryl and (C5-C14)-heteroaryl; R<7> is a direct bond; R<8> is hydroxy or -((C1-C4)-alkoxy; n is one; m is zero; i is one; q is zero; r is zero; s is zero; t is zero; in all their stereoisomeric forms and mixtures thereof in all ratios, and their physiologically tolerable salts and their prodrugs. 4. A process for the preparation of a compound as claimed in one or more of claims 1 to 3, comprising reacting a compound of the formula VI with a compound of the formula VIIa or with a compound of the formula VIIb wherein L<1> is a leaving group and B, G, X, Y, r, s and t are defined as in claims 1 to 3 but wherein functional groups can also be present in the form of precursor groups or in protected form. 5. A pharmaceutical composition, comprising at least one compound of the formula I as claimed in one or more of claims 1 to 3 and/or its physiologically tolerable salts and/or its prodrugs and a pharmaceutically acceptable carrier. 6. A compound of the formula I as claimed in one or more of claims 1 to 3 and/or its physiologically tolerable salts and/or its prodrugs for use as a vitronectin receptor antagonist. 7. A compound of the formula I as claimed in one or more of claims 1 to 3 and/or its physiologically tolerable salts and/or its prodrugs for use as an inhibitor of bone resorption, for the therapy or prophylaxis of osteoporosis, as an inhibitor of tumor growth or tumor metastasis, as an antiinflammatory, or for the therapy or prophylaxis of cardiovascular disorders, restenosis, arteriosclerosis, nephropathies, retinopathies, psoriasis or rheumatoid arthritis.