C - Chemistry – Metallurgy – 07 – C
Patent
C - Chemistry, Metallurgy
07
C
C07C 259/06 (2006.01) A61K 31/16 (2006.01) A61K 31/195 (2006.01) A61K 31/33 (2006.01) C07C 237/22 (2006.01) C07C 259/08 (2006.01) C07C 275/16 (2006.01) C07C 279/14 (2006.01) C07C 323/60 (2006.01) C07D 207/16 (2006.01) C07D 209/20 (2006.01) C07D 211/60 (2006.01) C07D 213/56 (2006.01) C07D 233/88 (2006.01) C07D 263/48 (2006.01) C07D 277/30 (2006.01) C07D 277/42 (2006.01) C07D 295/15 (2006.01) C07D 307/24 (2006.01) C07D 333/38 (2006.01) C07D 401/12 (2006.01) C07D 403/12 (2006.01) C07D 413/12 (2006.01) C07D 417
Patent
CA 2218380
The present invention provides hydroxamic acids and carbocyclic acids and derivatives thereof and to pharmaceutical compositions and methods of use of these compounds for the inhibition of matrix metalloproteinases, such as stromelysin, and inhibit the production of tumor necrosis factor alpha, and for the treatment of arthritis and other inflammatory diseases. These compounds are represented by formula (I), wherein: A is -C(R1) (R1a)CONHOH or - CH(R11)C(R9)(R9a)CO2H; Q is CONHR13; R2 is selected from: C1-C8 alkyl substituted with O-2R17b; -O-(C1-C8 alkyl)-R20; -S-(C1-C8 alkyl)-R20; -CH2O- (C1-C8 alkyl)-R20; -CH2S-(C1-C8 alkyl)-R20; R3 is selected from hydrogen, or C1-C6 alkyl substituted with 0-3 R4; R14 is selected from hydrogen, methyl or ethyl.
L'invention porte sur de nouveaux acides hydroxamiques et carboxyliques et leurs dérivés, et sur des compositions pharmaceutiques et méthodes utilisant ces composés: comme inhibiteurs des métalloprotéinases matricielles telles que la stromélysine, comme inhibiteurs de la production du facteur alpha de nécrose tumorale (TNF), et pour le traitement de l'arthrite et autres maladies inflammatoires associées. Ces nouveaux composés sont représentés par la formule (I) dans laquelle: A est -C(R?1¿), (R?1a¿) CONHOH ou -CH(R?11¿)C(R?9¿)(R?9a¿)CO¿2?H; Q est -CONHR?13¿, R?2¿ est choisi parmi C¿1?-C¿8? alkyle substitué par O-2R?17b¿, -O-(C¿1?-C¿8? alkyle)-R?20¿, -S-(C¿1?-C¿8? alkyle)-R?20¿, -CH¿2?O-(C¿1?-C¿8? alkyle)-R?20¿, -CH¿2?S-(C¿1?-C¿8? alkyle)-R?20¿; R?3¿ est choisi parmi hydrogène ou C¿1?-C¿6? alkyle substitué par 0-3 R?4¿; R?14¿ est choisi parmi hydrogène, méthyle ou éthyle.
Cherney Robert Joseph
Decicco Carl Peter
Jacobson Irina Cipora
Dimock Stratton Llp
Du Pont Pharmaceuticals Company
The Dupont Merck Pharmaceutical Company
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