Substituted 4-arylbutyric acid derivatives as matrix...

Details Substituted 4-arylbutyric acid derivatives as matrix... Substituted 4-arylbutyric acid derivatives as matrix...

C - Chemistry, Metallurgy

07

C

C07C 59/84 (2006.01) A61K 31/19 (2006.01) A61K 31/41 (2006.01) A61K 31/53 (2006.01) C07C 59/90 (2006.01) C07C 323/62 (2006.01) C07D 209/48 (2006.01) C07D 237/32 (2006.01) C07D 253/04 (2006.01) C07D 253/08 (2006.01) C07D 263/44 (2006.01) C07D 263/58 (2006.01) C07D 275/06 (2006.01) C07D 277/34 (2006.01)

Patent

CA 2253795

Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have generalized formula (I) wherein R1 represents C6-C12 alkyl; C5-C12 alkoxy; C5-C12 alkylthio; a polyether of formula R2O(C2H4O)a- in which a is 1 or 2 and R2 is C1-C5 alkyl, phenyl, or benzyl; and substituted alkynyl of formula R3(CH2)b-CC-; in which b is 1-10 and R3 is H-, HO-, or R4O- in which R4 is C1-C3 alkyl, phenyl, or benzyl. The alkyl, phenyl, and benzyl portions of R1 may bear at least one pharmaceutically-acceptable substituent. The subscript n is 2-4. R5 represents phenyl; imidoyl of 4-12 carbon atoms; (3H)-benzo-1,2,3-triazin-4-on-3-yl; N- saccharinyl; (2H)-phthalazin-1-on-2-yl; 2-benzoxazolin-2-on-3-yl; 5,5- dimethyloxazolidine-2,4-dion-3-yl; and thiazolidine-2,4-dion-3-yl; with the phenyl and benzo portions of R5 permissibly bearing at least one pharmaceutically-acceptable substituent. Pharmaceutically acceptable salts of these materials are also included.

Inhibiteurs des métalloprotéases matricielles, compositions pharmaceutiques les contenant, et leur procédé d'utilisation pour traiter une variété d'états physiologiques. Les composés selon l'invention répondent à la formule générale (I) dans laquelle R?1¿ représente alkyle C¿6?-C¿12?; alcoxy C¿5?-C¿12?; alkylthio C¿5?-C¿12?; un polyéther de formule R?2¿O(C¿2?H¿4?O)¿a?- dans laquelle a vaut 1 ou 2 et R?2¿ représente alkyle C¿1?-C¿5?, phényle ou benzyle; et un alcynyle substitué de la formule R?3¿(CH¿2?)¿b?-C?C-; b valant 1-10 et R?3¿ représentant H-, HO-, ou R?4¿O-, R?4¿ représentant alkyle C¿1?-C¿3?, phényle ou benzyle. Les parties alkyle, phényle et benzyle de R?1¿ peuvent porter au moins un substituant pharmaceutiquement acceptable. L'indice n vaut 2 à 4. R?5¿ représente phényle; imidoyle contenant 4-12 atomes de carbone; (3H)-benzo-1,2,3-triazin-4-on-3-yl; N-saccharinyle; (2H)-phtalazin-1-on-2-yle; 2-benzoxazolin-2-on-3-yle; 5,5-diméthyloxazolidine-2,4-dion-3-yle; et thiazolidine-2,4-dion-3-yle; les parties phényle et benzo de R?5¿ pouvant porter au moins un substituant pharmaceutiquement acceptable. Les sels pharmaceutiquement acceptables de ces substances sont également décrits.

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