Alkynyl containing hydroxamic acid derivatives, their...

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 211/66 (2006.01) A61K 31/35 (2006.01) A61K 31/351 (2006.01) A61K 31/4427 (2006.01) A61K 31/445 (2006.01) A61K 31/4523 (2006.01) A61K 31/4525 (2006.01) A61K 31/4535 (2006.01) A61K 31/454 (2006.01) A61K 31/4545 (2006.01) A61K 31/496 (2006.01) A61K 31/5377 (2006.01) A61P 1/00 (2006.01) A61P 1/16 (2006.01) A61P 9/00 (2006.01) A61P 9/10 (2006.01) A61P 17/00 (2006.01) A61P 19/00 (2006.01) A61P 19/02 (2006.01) A61P 19/08 (2006.01) A61P 25/00 (2006.01) A61P 27/02 (2006.01) A61P 29/00 (2006.01) A61P 31/04 (2006

Patent

CA 2356313

Compounds of formula (I) wherein R1 is hydrogen, aryl, heteroaryl, alkyl of 1- 8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms, or -C4-C8-cycloheteroalkyl; R2 and R3 are hydrogen, alkyl of 1-6 carbon atoms, -CN, or CCH; R8, R9, R10 and R11 are hydrogen, aryl or heteroaryl, cycloalkyl of 3-6 carbon atoms, -C4-C8- cycloheteroalkyl, alkyl of 1-18 carbon atoms, alkenyl of 2-18 carbon atoms, alkynyl of 2-18 carbon atoms; with the proviso that one of the pairs R8 and R9, R9 and R10 or R10 and R11, together with the carbon atom or atoms to which they are attached, form a cycloalkyl ring of 3-6 carbon atoms, or a -C4-C8- cycloheteroalkyl ring; R12 is hydrogen, aryl or heteroaryl, cycloalkyl of 3-6 carbon atoms; -C4-C8-cycloheteroalkyl, or alkyl of 1-6 carbon atoms; A, X are O, S, SO, SO2, NR7, or CH2; Y is aryl or heteroaryl, with the proviso that A and X are not bonded to adjacent atoms of Y; and n is 0-2; or a pharmaceutically acceptable salt thereof; useful in the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.

La présente invention concerne des composés représentés par la formule générale (I), ou certains de leurs sels pharmaceutiquement admis. Dans cette formule générale, R¿1? est hydrogène, aryle, hétéroaryle, C¿1?-C¿8? alkyle, C¿2?-C¿6? alcényle, C¿2?-C¿6? alkynyle, C¿3?-C¿6? cycloalkyle, ou C¿4?-C¿8? cyclohétéroalkyle; R¿2? et R¿3? sont hydrogène, C¿1?-C¿6? alkyle, -CN, ou CCH; R¿8?, R¿9?, R¿10? et R¿11? sont hydrogène, aryle ou hétéroaryle, C¿3?-C¿6? cycloalkyle, C¿4?-C¿8? cyclohétéroalkyle, C¿1?-C¿18? alkyle, C¿1?-C¿28? alcényle, C¿2?-C¿28? alkynyle; toutefois, l'un des couples R¿8?-R¿9?, R¿9?-R¿10? ou R¿10?-R¿11?, forment, avec les atomes de carbone auxquels ils sont attachés, un C¿3?-C¿6? cycloalkyle, ou un C¿4?-C¿8? cyclohétéroalkyle; R¿12? est hydrogène, aryle ou hétéroaryle, C¿3?-C¿6? cycloalkyle; C¿4?-C¿8? cyclohétéroalkyle, ou C¿1?-C¿6? alkyle; A et X sont O, S, SO, SO¿2?, NR¿7?, ou CH¿2?; Y est aryle ou hétéroaryle, A et X ne devant pas être liés aux atomes adjacents de Y; enfin, n est un entier valant de 0 à 2. Ces composés, ou les sels considérés, conviennent au traitement de l'arthrite, de la métastase tumorale, de l'ulcération tissulaire, des anomalies de cicatrisation, de la parodontopathie, d'affections osseuses, du diabète (insulinorésistant) et de l'infection par le VIH.

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