| abstract |
The present invention relates to 5-spiro-pyrimidine-2,4,6-trionmetalloproteinase inhibitors of formula (I), wherein said <RTIgt; A </RTI> ring is a 5-7 membered heterocyclic ring optionally substituted; The invention further relates to pharmaceutical compositions and methods for treating inflammation, cancer and other disorders. X is C 6 -C 10 aryl or C 1 -C 10 heteroaryl; Y is a bond or an oxygen or sulfur atom or C = O, SO2, S = O, -CH2-, -CH2O-, -CH2S-, -CH2SO-, -CH2SO2-, -CH = CH-, -C < C- or -O (CH 2) n -, -S (CH 2) n -, -SO (CH 2) n -, -SO 2 (CH 2) n -, -NR 14 -, -NR 14 (CH 2) n -, - CH 2 [N (R 14)] -, -CH 2 (CH 2) n -, - [N (R 14)] - SO 2 - or -SO 2 [N (R 14)] -; Z is C 6 -C 10 aryl, C 3 -C 8 cycloalkyl, C 1 -C 10 heterocyclyl or C 1 -C 10 heteroaryl; wherein said C3-C8 cycloalkyl or C1-C10 heterocyclyl may be optionally substituted on carbon by one or two carbon-carbon double bonds; G is R15- (CR16R17) p; wherein G is a single substituent on any ring carbon atom of Z that is capable of forming an additional bond and is oriented at a point other than alpha to the ring attachment point of Z to Y, p is an integer from 0 to 4. SHE |