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US 2006/0052398 A1Published application
Novel vitronectin receptor antagonist derivatives, method for preparing same, use thereof as medicines and pharmaceutical compositions containing same
AssigneeGalapagos NV
InventorsJean-Marie Ruxer, Jean Lefrancois, Bertrand Heckmann
Life of this patent
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Abstract
A subject of the invention is the compounds of formula (I): in which R1, R2, R3, R4 and G have the meanings indicated in the description, their preparation process, their use as medicaments having an antagonist activity on the vitronectin receptor and the pharmaceutical compositions containing them.
Claims21
1) The compounds of formula (I)
- in all their isomeric forms, alone or in mixture, as well as their physiologically acceptable addition salts, in which
- G represents
- R7R8N—C(═NR6)—NH—CO—
- Het-NH—CO—;
- Het-NH—CH2—,
- Het-,
- Het representing a monocyclic or polycyclic system, each ring being constituted by 4 to 10 aromatic or non aromatic members, the ring or at least one of the rings containing 1 to 4 nitrogen atoms, substituted or non substituted by one or more R9 groups
- R1 represents a hydrogen atom;
- a (C5-C14)-aryl;
- (C5-C14)-aryl-(C1-C4)-alkyl-group;
- an amino radical non substituted or monosubstitufedordisubstituted by an alkyl radical and/or an acyl radical containing 1 to 4 carbon atoms;
- R2 represents a hydrogen atom;
- a halogen atom;
- a nitro group;
- an alkyl radical containing 1 to 4 carbon atoms;
- an amino radical non substituted or monosubstituted or disubstituted by an alkyl radical and/or an acyl radical containing 1 to 4 carbon atoms;
- a-(CH2)0-2—CO2R5 group;
- or a —(CH2)0-2—OR5 group;
- R3 represents
- a hydrogen atom
- a-CO2R5 radical,
- a-SO2R5 radical or
- a monocyclic or polycyclic system, each ring being constituted by 4 to 10 aromatic or non aromatic members, the ring or at least one of the rings containing 1 to 4 heteroatoms chosen from N, O or S, substituted or non substituted by one or more R9 radicals,
- R4 represents OH;
- (C1-C8)-alkoxy-;
- (C5-C14)-aryl-(C1-C4)-alkyloxy-;
- (C5-C14)-aryloxy-;
- (C3-C12)-cycloalkyloxy;
- (C3-C12)-cycloalkyl-(C1-C4)-alkyloxy-;
- (C1-C8)-alkylcarbonyloxy-(C1-C4)-alkyloxy-;
- (C5-C14)-aryl-(C 1-C4)-alkylcarbonyloxy-(C1-C4) alkyloxy-;
- (C1-C8)dialkylaminocarbonylmethyloxy-;
- (C5-C14)-aryl-(C1-C4)-dialkylaminocarbonylmethyloxy-;
- an amino radical non substituted or monosubstituted or disubstituted by a (C1-C4)-alkyl and/or (C5-C14)-aryl and/or (C5-C14)-aryl-(C1-C4)-alkyl- radical and/or a (C1-C5)-acyl radical;
- or the remainder of an amino acid D or L;
- R5 represents (C1-C8)-alkyl;
- (C5-C14)-aryl;
- (C5-C14)-aryl-(C1-C4)-alkyl-;
- (C3-C12)-cycloalkyl or (C3-C12)-cycloalkyl-(C1-C4)-alkyl-, bicycloalkyl-(C1-C4)-alkyl-, tricycloalkyl-(C1-C4)-alkyl-, the said aryl, alkyl, cycloalkyl, bicycloalkyl and tricycloalkyl radicals being non substituted or substituted by one or more chosen R9 groups;
- R represents a hydrogen atom;
- a hydroxyl;
- nitro, (C1-C6)-alkyl-O—CO—;
- or (C1-C6)-alkyl-O—CO—O— group:
- R7 and R8, independently of one another represent a hydrogen atom or a (C1-C6)-alkyl radical non substituted or substituted by R9;
- R9 represents halogen;
- amino ;
- nitro ;
- hydroxyl, (C1-C4)-alkyloxy-;
- (C1-C4)-alkylthio-;
- carboxy;
- (C1-C4)-alkyloxycarbonyl-;
- (C1-C8)-alkyl non substituted or substituted by one or more halogen atoms, (C5-C14)-aryl, (C5-C,4)-aryl-(C1-C4)-alkyl-
- it being understood that the aryl radicals can be non substituted or substituted by one or more identical or different radicals chosen from (C1-C8)-alkyl, in particular (C1-C4)-alkyl, hydroxyl, (C1-C8)-alkyloxy, (C1-C8)-alkylthio, halogen chosen from fluorine, chlorine and bromine, nitro, amino, (C1-C4)-alkylamino, di-(C1-C4)-alkylamino, trifluoromethyl, methylenedioxy, cyano, aminocarbonyl, (C1-C4)-alkylaminocarbonyl, di-(C1-C4)-alkylaminocarbonyl, carboxy, (C1-C4)-alkoxycarbonyl, phenyl, phenoxy, benzyl and benzyloxy.
50 more elements
Dependencies are inferred from the claim text.