Alkynyl containing hydroxamic acid derivatives, their preparation and their use as matrix metalloproteinase (mmp) inhibitors/tnf-alpha converting enzyme (tace) inhibitors

摘要

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 whi ch 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 ar e 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.