Substituted oxobutyric acids as matrix metalloprotease inhibitor

Details Substituted oxobutyric acids as matrix metalloprotease inhibitor Substituted oxobutyric acids as matrix metalloprotease inhibitor

1997-05-15

1999-08-03

Geist, Gary

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

514417, 514570, 544220, 548473, 562459, 562463, A61K 3153, C07D25100, C07D20948, C07C 6532

Patent

active

059325771

ABSTRACT:
The present invention provides pharmaceutical compositions and methods for treating certain conditions associated with matrix metalloproteases comprising administering an amount of a compound or composition of the invention which is effective to inhibit the activity of at least one matrix metalloprotease, resulting in achievement of the desired effect. The compounds of the present invention are either of the generalized formula: ##STR1## wherein y is 0, 2, or, 3, r is 0-6, Z is (CH.sub.2).sub.7 or (CH.sub.2).sub.e --C.sub.6 H.sub.4 --(CH.sub.2).sub.f, wherein e is 0-1 and f is 0-5, and R.sup.15 is --H, --Cl, --OMe or ##STR2## wherein n is 0-4, R.sup.17 is C.sub.2 H.sub.5, alkyl, benzyl, and R.sup.16 is ##STR3## wherein t is 0-2, x is 0-4, and R.sup.4 is one of the following: halide, alkyl of 1-6 carbons, OR, NR.sub.2, NO.sub.2 (R=H or alkyl of 1-6 carbons).

REFERENCES:
Sahoo, et al., Inhibition of Matrix Metalloproteinases by N-Carboxyalkyl Dipeptides: Enhanced Potency and Selectivity with Substituted P.sub.1 ' Homophenylanines, Biorganic & Medicinal Chemistry Letters, 5(20), 2441-2446 (1995).
Child, et al., Fenbufen, a New Anti-Inflammatory Analgesic: Synthesis and Structure-Activity Relationships of Analogs, Journal of Pharmaceutical Sciences, 66(4), 466-476 (1977).

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