| Abstract: | Compounds of formula ##STR1## wherein W is --OH or --NHOH; X is a heterocycle with the proviso that when X is a nitrogen containing heterocycle, the heterocycle is attached to the (CH.sub.2).sub.m moiety by a ring nitrogen, --CONR.sub.2 R.sub.3, --NR.sub.1 COR.sub.2, --NR.sub.1 SO.sub.2 R.sub.2, --NR.sub.1 CONR.sub.2 R.sub.3, --NR.sub.1 COOR.sub.4, heteroarylthio, alkylthio, arylalkylthio, heteroarylalkylthio, heterocycloalkylalkylthio, heterocycloalkylthio or arylthio; Y is carbon, nitrogen, oxygen or sulfur, provided that when Y is carbon, n is 2; Z is alkyl, aryl, alkoxy, aryloxy, aralkoxyaryl, aralkoxyheteroaryl, heteroaryl, heterocycloalkyl, heteroaryloxy, --CONR.sub.2 R.sub.3, --NR.sub.1 COR.sub.2, --NR.sub.1 CONR.sub.2 R.sub.3, --OCONR.sub.2 R.sub.3, --NR.sub.1 COOR.sub.4, or --SO.sub.2 R.sub.2 ; R.sub.1 is hydrogen, alkyl, heterocycloalkylalkyl, aralkyl or heteroarylalkyl; R.sub.2 and R.sub.3 are independently R.sub.1, aryl or heteroaryl; or R.sub.2 and R.sub.3 taken together with the nitrogen atom to which they are attached form a 5- to 7-membered ring, which may optionally contain another heteroatom selected from oxygen, nitrogen and sulfur; R.sub.4 is alkyl, heterocycloalkylalkyl, aralkyl, aryl or heteroaryl; m represents an integer from one to six; n represents the integer one or two; and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; and a method of inhibiting matrix-degrading metalloproteinases in mammals using such compounds. Compounds of formula I are inhibitors of matrix-degrading metalloproteinases and are useful for the treatment of conditions related thereto. |
| Inventor(s): | Kukkola; Paivi Jaana (Whitehouse Station, NJ), Robinson; Leslie Anne (Del Mar, CA), Nakajima; Motowo (Ashiya, JP), Sakaki; Junichi (Takarazuka, JP) |
