US4599361A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Hydroxamic acid based collagenase inhibitors
Assignee: GD Searle LLC
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Filing: 1985-09-10
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Granted: 1986-07-08
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Expires: 2005-09-10
Abstract
Abstract This disclosure relates to a novel class of hydroxamic acid based collagenase inhibitor derivatives. The disclosure further relates to pharmaceutical compositions containing such compounds and to the use of such compounds and compositions in the treatment of collagenase induced diseases.
Inventors
- 👤 Jonathan P. Dickens
- 👤 David K. Donald
- 👤 Geoffrey Kneen
- 👤 William R. McKay
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-10 01:28
CPC Classifications
C; C07; C07C; C07C233/00; C07C233/01; C07C233/02; C07C237/00
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
112 words
A compound of the formula ##STR26## wherein R 1 is C 1 -C 6 alkyl; R 2 is C 1 -C 6 alkyl, benzyl, benzyloxybenzyl, (C 1 -C 6 alkoxy)benzyl or benzyloxy(C 1 -C 6 alkyl); a is a chiral center with optional R or S stereochemistry; A is a ##STR27## group or a --(CR 3 ═CR 4 )-- group wherein b and c are chiral centers with optional R or S stereochemistry; R 3 is hydrogen, C 1 -C 6 alkyl, phenyl or phenyl(C 1 -C 6 alkyl) and R 4 is hydrogen or C 1 -C 6 alkyl, phenyl(C 1 -C 6 alkyl), cycloalkyl or cycloalkyl(C 1 -C 6 alkyl).
Claim 2
Dependent Claim
112 words
A compound of the formula ##STR26## wherein R 1 is C 1 -C 6 alkyl; R 2 is C 1 -C 6 alkyl, benzyl, benzyloxybenzyl, (C 1 -C 6 alkoxy)benzyl or benzyloxy(C 1 -C 6 alkyl); a is a chiral center with optional R or S stereochemistry; A is a ##STR27## group or a --(CR 3 ═CR 4 )-- group wherein b and c are chiral centers with optional R or S stereochemistry; R 3 is hydrogen, C 1 -C 6 alkyl, phenyl or phenyl(C 1 -C 6 alkyl) and R 4 is hydrogen or C 1 -C 6 alkyl, phenyl(C 1 -C 6 alkyl), cycloalkyl or cycloalkyl(C 1 -C 6 alkyl).
Claim 3
Dependent Claim
13 words
A compound according to claim 1 wherein chiral center a has S stereochemistry.
Claim 4
Dependent Claim
11 words
A compound according to claim 2 wherein A is a ##STR28##
Claim 5
Dependent Claim
15 words
A compound according to claim 3 wherein R 2 is (C 1 -C 6 alkoxy)benzyl.
Claim 6
Dependent Claim
36 words
A compound according to claim 4 wherein R 2 is 4-methoxybenzyl, R 4 is C 1 -C 4 alkyl and R 3 is hydrogen, C 1 -C 4 alkyl, phenyl or phenyl(C 1 -C 6 alkyl).
Claim 7
Dependent Claim
22 words
A compound according to claim 5 wherein R 1 is methyl, R 3 is hydrogen or methyl and R 4 is 2-methylpropyl.
Claim 8
Dependent Claim
11 words
A compound according to claim 6 wherein R 3 is hydrogen.
Claim 9
Dependent Claim
102 words
A compound according to claim 7 having the following NMR spectrum: NMR (d 6 -DMSO) 0.7-0.9 (6H, m, {CH 3 } 2 CH); 1.3 (1H, m, {CH 3 } 2 CH); 1.9-2.2 (3H, 2xm, CH 2 CH); 2.50 (3H, m, CHCH 2 CO, +CH 2 CHCO); 2.6 (2H, m, ArCH 2 ); 2.6 (3H, d, NHCH 3 ); 3.7 (3H, s, OCH 3 ); 4.3-4.4 (1H, m, ArCH 3 CH); 6.75-7.1 (4H, 2xd, J=8 Hz, aromatic); 7.9 (1H, m, NHCH 3 ); 8.05 (1H, d, CONHCH); 8.65 (1H, s, NHOH {D 2 O exchange}); 10.4 (1H, s, NHOH {D 2 O exchange}).
Claim 10
Dependent Claim
11 words
A compound according to claim 6 wherein R 3 is methyl.
Claim 11
Dependent Claim
106 words
A compound according to claim 9 having the following NMR spectrum: NMR (d 6 -DMSO) 0.64-0.92 (9H, m, {CH 3 } 2 CHCH 2 ); 1.30 (3H, m, CH 3 CH); 2.20-2.40 (2H, m, CH 3 CH and CH 3 CHCH); 2.45 (2H, m, ArCH 2 ); 2.55 (3H, d, J=4 Hz, NHCH 3 ); 3.68 (3H, s, OCH 3 ); 4.45 (1H, m, ArCH 2 CH); 6.80 and 7.16 (4H, two d's, J=7 Hz, aromatic); 7.72 (1H, m, NHCH 3 ); 8.18 (1H, d, J=7 Hz, CONHCH 3 ); 8.72 (1H, s, NHOH {D 2 O exchange}); 10.37 (1H, s, NHOH {D 2 O exchange}).
Claim 12
Dependent Claim
28 words
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.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1989-07-07 | 1990-01-06 | 1990-07-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1993-07-07 | 1994-01-06 | 1994-07-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1997-07-07 | 1998-01-06 | 1998-07-08 | $7700.00 | Window Closed / Lapsed |