Azacycloalkyl substituted acetic acid derivatives for use as...

C - Chemistry – Metallurgy – 07 – D

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C07D 211/16 (2006.01) A61K 31/445 (2006.01) A61K 31/4535 (2006.01) C07D 211/26 (2006.01) C07D 211/32 (2006.01) C07D 211/34 (2006.01) C07D 401/12 (2006.01) C07D 405/14 (2006.01) C07D 409/12 (2006.01) C07D 409/14 (2006.01) C07D 413/14 (2006.01) C07D 417/12 (2006.01)

Patent

CA 2440419

Compounds of the formula (I) wherein R represents OH or NHOH; R1 represents hydrogen, optionally substituted lower alkyl, aryl-lower alkyl, cycloalkyl- lower alkyl, or acyl derived from a carboxylic acid, from a carbonic acid, from a carbamic acid of from a sulfonic acid; R2 represents biarylsulfonyl or aryloxyarylsufonyl; R3 represents hydrogen, optionally substituted lower alkyl, aryl-lower alkyl, cycloalkyl-lower alkyl or acyl derived from a carboxylic acid, from a carbonic acid or form a carbamic acid; R4 and R5 represent independently hydrogen, lower alkyl, lower alkoxycarbonyl, aryl- lower alkyl or cycloalkyl-lower alkyl; m is zero, 1, 2 or 3; pharmaceutically acceptable prodrug derivatives thereof; pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; and their use for inhibiting matrix degrading metalloproteinases and preventing or treating matrix metalloproteinase dependent conditions in mammals.

Cette invention concerne des composés représentés par la formule (I). Dans cette formule, R représente OH ou NHOH; R¿1? représente hydrogène, alkyle inférieur éventuellement substitué, aryl-alkyle inférieur, cycloalkyle-alkyle inférieur, ou acyle dérivé d'un acide carboxylique, d'un acide carbonique, d'un acide carbamique ou d'un acide sulfonique; R¿2? Représente biarylsulfonyle ou aryloxyarylsufonyle; R¿3? représente hydrogène, alkyle inférieur éventuellment substitué, aryle-alkyle inférieur, cycloalkyle-alkyle inférieur ou un acyle tiré d'un acide carboxylique, d'un acide carbonique ou d'un acide carbamique; R¿4? et R¿5? représentent chacun indépendamment hydrogène, alkyle inférieur, alkoxycarbonyle inférieur, aryle-alkyle inférieur ou cycloalkyle-alkyle inférieur; m vaut 0, 1, 2 ou 3. L'invention concerne également des dérivés promédicaments pharmaceutiquement acceptables, des sels pharmaceutiquement acceptables de ces composés, ainsi que des compositions renfermant lesdits composés. L'invention concerne enfin l'utilisation de ces composés aux fins d'inhibition de métalloprotéinases à dégradation matricielle ainsi que la prévention et le traitement, chez des mammifères, de pathologies dépendant de métalloprotéinases matricielles.

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