Substituted cyclic amine metalloprotease inhibitors

#This invention is directed to compounds which are useful in treating diseases associated with metalloprotease activity, particularly zinc metalloprotease activity.

#Backgound

#A number of structurally related metalloproteases [MPs] effect the breakdown of structural proteins. These metalloproteases often act on the intercellular matrix, and thus are involved in tissue breakdown and remodeling. Such proteins are referred to as metalloproteases or MPs. There are several different families of MPs, classified by sequence homology. Several families of known MPs, as well as examples thereof, are disclosed in the art.

#Compounds are analyzed using 1H and 13C NMR, Elemental analysis, mass spectra and/or IR spectra, as appropriate.

#Typically tetrahydrofuran (THF) is distilled from sodium and benzophenone, diisopropylamine is distilled from calcium hydride and all other solvents are purchased as the appropriate. Chromatography is performed on silica gel (70-230 mesh; Aldrich) or (230-400 mesh; Merk) as appropriate. Thin layer chromatography analysis (TLC) is performed on glass gel plates (200-300 mesh; Baker) and visualized with UV or 5% phosphomolybdic acid in EtOH.

#The following chart shows the structure of compounds made according to the description in Examples 1-19 described below: 1 5 Example * (configuration) Y Z 1 d a-OH H 2 d b-OH H 3 l a-OH H 4 l b-OH H 5 d b-OMe H 6 d b-(2-benzathiazole) H 7 d a-(2-benzathiazole) H 8 d b-2(3N-methyl-imidazole) H 9 d a-2(3N-methyl-imidazole) H 10 d b-OPh H 11 d b-O(C6H4)OCH2Ph H 12 d b-O(2-(C6H4)NHPh) H 13 d b-O(3-Pyridyl) H 14 d b-SPh H 15 d b-S(4-C6H4OMe) H 16 d b-S(3-C6H4OMe) H 17 d a-OCH2OCH2CH3 H 18 d a-OCH2OCH2Ph H 19 d a-OCH2OCH2CH3OCH3 H 20 d b-SH H 21 racemic H phenyl 22 d a-OH, b-Et H 23 d a-OH, b-Ph H 24 d b-O(4-C6H4-Octyl) H 25 d a-OH gem-(CH3)2