Isophthalic acid derivatives as matrix metalloproteinase...

C - Chemistry – Metallurgy – 07 – C

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C07C 235/60 (2006.01) A61K 31/166 (2006.01) A61K 31/194 (2006.01) A61K 31/235 (2006.01) A61K 31/36 (2006.01) A61K 31/433 (2006.01) A61P 1/00 (2006.01) A61P 9/00 (2006.01) A61P 19/00 (2006.01) A61P 35/00 (2006.01) C07C 69/80 (2006.01) C07C 69/90 (2006.01) C07C 69/92 (2006.01) C07C 229/60 (2006.01) C07C 233/66 (2006.01) C07C 233/69 (2006.01) C07C 233/73 (2006.01) C07C 233/75 (2006.01) C07C 233/78 (2006.01) C07D 213/30 (2006.01) C07D 285/14 (2006.01) C07D 317/54 (2006.01)

Patent

CA 2435376

Selective MMP-13 inhibitors are isophthalic acid derivatives of the formula (I) wherein: R1, R2, and R3 independently are hydrogen, halo, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, NO2, NR4R5, CN, or CF3; E is independently O or S; A and B independently are OR4 or NR4R5; each R4 and R5 independently are H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (CH2)n aryl, (CH2)n cycloalkyl, (CH2)n heteroaryl, or R4 and R5 when taken together with the nitrogen to which they are attached complete a 3- to 8-membered ring, optionally containing heteroatom selected from O, S, or NH, and optionally substituted or unsubstituted; n is 0 to 6; or a pharmaceutically acceptable salt thereof. The compounds are useful for treating diseases in a mammal that are mediated by MMP enzymes.

L'invention concerne des inhibiteurs MMP-13 sélectifs qui sont des dérivés d'acide isophthalique de formule (I). Dans cette formule, R?1¿, R?2¿, et R?3¿ représentent indépendamment l'hydrogène, l'halogène, un hydroxy, C¿1?-C¿6? alkyle, C¿1?-C¿6? alcoxy, C¿2?-C¿6? alcényle, C¿2?-C¿6? alkynyle, NO¿2?, NR?4¿R?5¿, CN, ou CF¿3?, E représente indépendamment O ou S, A et B représentent indépendamment OR?4¿ ou NR?4¿R?5¿, R?4¿ et R?5¿ représentent respectivement et indépendamment H, C¿1?-C¿6? alkyle, C¿2?-C¿6? alcényle, C¿2?-C¿6? alkynyle, (CH¿2?)¿n? aryle, (CH¿2?)¿n? cycloalkyle, (CH¿2?)¿n? hétéroaryle, ou R?4¿ et R?5¿, lorsqu'ils sont avec l'azote auquel ils sont attachés, complètent un anneau comprenant 3 à 8 éléments, contenant facultativement un hétéroaome sélectionné parmi O, S, ou NH, et facultativement substitué ou non substitué, n est un nombre entier compris entre 0 et 6, ou un sel correspondant acceptable pharmaceutiquement. On utilise les composés pour traiter des maladies chez un mammifère, lesdits composés étant médiés par des enzymes MMP.

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