Claims for Patent: 4,595,700

Summary for Patent: 4,595,700

Title:	Thiol based collagenase inhibitors
Abstract:	This invention relates to compounds of the formula: ##STR1## wherein R.sub.1 represents lower alkyl, phenyl or phenyl lower alkyl; R.sub.2 and R.sub.4 represent lower alkyl; and R.sub.3 represents lower alkyl, benzyloxyalkyl, alkoxybenzyl or benzyloxybenzyl wherein the oxyalkyl or alkoxy moiety contain 1 to 6 carbon atoms; and a, b, and c represent chiral centers with optional R or S stereochemistry. These compounds inhibit collagenase and are useful in the treatment of arthritis. Also disclosed are processes for manufacture of the compounds and pharmaceutical compositions containing them.
Inventor(s):	Donald; David K. (High Wycombe, GB3), Hann; Michael M. (Watlington, GB3), Saunders; John (Ickford, GB3), Wadsworth; Harry J. (High Wycombe, GB3)
Assignee:	G. D. Searle & Co. (Skokie, IL)
Application Number:	06/703,973
Patent Claims:	1. A compound of the formula ##STR23## wherein R.sub.1 represents lower alkyl, phenyl or phenyl lower alkyl; R.sub.2 and R.sub.4 represent lower alkyl; and R.sub.3 represents lower alkyl, benzyloxyalkyl, alkoxybenzyl or benzyloxybenzyl wherein the oxyalkyl or alkoxy moiety contain 1 to 6 carbon atoms; and a, b, and c, represent chiral centers with optional R or S stereochemistry. 2. A compound according to claim 1 of the formula ##STR24## 3. A compound according to claim 2 further defined by having NMR spectral peaks at [.delta.(CDCl.sub.3 ]0.86 (6H, d, J=5 Hz, (CH.sub.3).sub.2 CH); 1.2 (3H, d, J=6 Hz, CH.sub.3 CHSH); 1.54 (3H, m, CHCH.sub.2); 2.2 (1H, m, CHCO); 2.72 (3H, d, J=4 Hz NHCH.sub.3); 3.02 (3H, m, CH.sub.2 C.sub.6 H.sub.4, CHSH); 3.62 (3H, s, CH.sub.3 7.0); 4.6 (1H, q, J=5 Hz NHCHCO); 6.78 and 7.10 (4H, each d, each J=9 Hz, (C.sub.6 H.sub.4). 4. A compound according to claim 2 further defined by having NMR spectral peaks at [.delta.(CDCl.sub.3)] 0.78 (6H, m, (CH.sub.3).sub.2 CH); 1.28 (3H, d, J=5 Hz, CH.sub.3 CHSH); 1.16 (3H, m, CH CH.sub.2); 2.16 (1H, m, CHCO); 2.74 (3H, d, J=5 Hz, CH.sub.3 NH); 3.02 (3H, m, CHSH,CH.sub.2 C.sub.6 H.sub.4) 3.76 (3H, s, CH.sub.3 O); 4.68 (1H, m, NHCHCO); 6.3 (1H, m, NH); 6.52 (1H, m, NH); 6.78 and 7.08 (4H, each d, each J=8 Hz, C.sub.6 H.sub.4). 5. A compound according to claim 1 of the formula ##STR25## 6. A compound according to claim 1 having the formula ##STR26## 7. A compound according to claim 1 which is ##STR27## 8. A compound according to claim 6 comprising a pair of diastereomers having NMR spectral peaks at [.delta.(CDCl.sub.3 ] 0.92 (6H, m, (CH.sub.3).sub.2 CH); 1.14 and 1.15 (3H each d, each J=6 Hz CH.sub.3 CHSH); 1.36 (3H, d, J=6 Hz, CH.sub.3); 1.58 (3H, m, CH.sub.2 CH); 2.3 (1H, m. CHCO); 2.82 (3H, d, J=5 Hz, NHCH.sub.3); 3.12 (1H, m, CHO); 4.14 (1H, m. CHS); 4.86 (1H, m, NHCHCO); 4.66 (2H, s, CH.sub.2 C.sub.6 H.sub.5); 6.48 (1H, m. NH); 6.7 (1H, m, NH) and 7.32 (5H, m, C.sub.6 H.sub.5). 9. A compound according to claim 1 having the formula ##STR28## 10. A compound according to claim 1 having the formula ##STR29## 11. A method of promoting an antiarthritic effect in a mammal in need thereof comprising administering thereto a collagenase inhibiting effective amount of a compound according to claim 1.

Details for Patent 4,595,700

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2004-12-21