US4981865A
Expired / Lapsed
US
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N-hydroxyamide, N-hydroxythioamide, hydroxyurea, and N-hydroxythiourea derivatives of selected nsaids as antiinflammatory agents
Assignee: Warner Lambert Co LLC
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Filing: 1989-05-26
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Granted: 1991-01-01
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Expires: 2009-05-26
Abstract
Abstract The present invention includes N-hydroxyamide, N-hydroxyurea, N-hydroxythioamide, and N-hydroxythiourea derivatives of fenamates, indomethacin, cicloprofen, oxepinac, and indoprofen as dual inhibitors or selective inhibitors of cyclooxygenase and 5-lipoxygenase.
Inventors
- 👤 Thomas R. Belliotti
- 👤 Wiaczeslaw A. Cetenko
- 👤 David T. Connor
- 👤 Daniel L. Flynn
- 👤 Catherine R. Kostlan
- 👤 James B. Kramer
- 👤 Jagadish C. Sircar
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 10:02
CPC Classifications
C; C07; C07C; C07C275/00; C07C275/64; C07C215/00; C07C215/68; C07C223/00; C07C223/06; C07C225/00; C07C225/22; C07C229/00; C07C229/52; C07C229/54; C07C229/56; C07C229/58; C07C239/00; C07C239/08; C07C239/10; C07C239/16; C07C251/00; C07C251/32; C07C251/34; C07C251/48; C07C259/00; C07C259/04; C07C259/06; C07C271/00; C07C271/06; C07C271/08; C07C271/10; C07C271/12; C07C271/20; C07D; C07D209/00; C07D209/02; C07D209/04; C07D209/10; C07D209/14; C07D209/44; C07D209/46; C07D313/00; C07D313/02; C07D313/06; C07D313/10; C07D313/12; C07C2603/00; C07C2603/02; C07C2603/04; C07C2603/06; C07C2603/10; C07C2603/12; C07C2603/18
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
189 words
A compound of the formula (I) ##STR40## and a pharmaceutically acceptable acid addition or base salt thereof; wherein Ar is (1) ##STR41## wherein R 1 , R 2 , and R 3 are independently hydrogen, fluoro, chloro, bromo, iodo, CF 3 , lower alkyl, CN, hydroxy, lower alkoxy, --S(O)q-lower alkyl wherein q is an integer of 0, 1, or 2, NO 2 or NR 4 R 5 wherein R 4 or R 5 are independently hydrogen, lower alkyl, lower acyl; ##STR42## Y is O or S; W is lower alkyl, aryl, aralkyl, lower alkoxy, NR 6 R 7 , (CH 2 ) n CO 2 R 7 , NH(CH 2 ) m CO 2 R 7 , NH(CH 2 ) p NR 6 R 7 , or NHCH 2 CH═CH 2 wherein R 5 is independently as defined above, R 6 and R 7 are independently hydrogen or lower alkyl, n is an integer of from 0 to 3, m is an integer of from 0 to 3; and p is an integer of 2 or 3; with the proviso that Y cannot be sulfur when n is 0.
Claim 2
Dependent Claim
189 words
A compound of the formula (I) ##STR40## and a pharmaceutically acceptable acid addition or base salt thereof; wherein Ar is (1) ##STR41## wherein R 1 , R 2 , and R 3 are independently hydrogen, fluoro, chloro, bromo, iodo, CF 3 , lower alkyl, CN, hydroxy, lower alkoxy, --S(O)q-lower alkyl wherein q is an integer of 0, 1, or 2, NO 2 or NR 4 R 5 wherein R 4 or R 5 are independently hydrogen, lower alkyl, lower acyl; ##STR42## Y is O or S; W is lower alkyl, aryl, aralkyl, lower alkoxy, NR 6 R 7 , (CH 2 ) n CO 2 R 7 , NH(CH 2 ) m CO 2 R 7 , NH(CH 2 ) p NR 6 R 7 , or NHCH 2 CH═CH 2 wherein R 5 is independently as defined above, R 6 and R 7 are independently hydrogen or lower alkyl, n is an integer of from 0 to 3, m is an integer of from 0 to 3; and p is an integer of 2 or 3; with the proviso that Y cannot be sulfur when n is 0.
Claim 3
Dependent Claim
12 words
A compound of claim 1 wherein X is CH 2 , ##STR43##
Claim 4
Dependent Claim
12 words
A compound of claim 1 wherein X is CH═CHCH 2 or ##STR44##
Claim 5
Dependent Claim
9 words
A compound of claim 1 wherein Y is oxygen.
Claim 6
Dependent Claim
9 words
A compound of claim 1 wherein Y is sulfur.
Claim 7
Dependent Claim
27 words
A compound of claim 1 wherein Ar is ##STR45## wherein R 1 , R 2 , R 3 , X, Y and W are as defined above.
Claim 8
Dependent Claim
18 words
A compound of claim 1 wherein Ar is ##STR46## wherein X, Y and W are as defined above.
Claim 9
Dependent Claim
8 words
A compound of claim 6 which is N-[[2-[(2,6-dichloro-3-methylphenyl)amino]phenyl]methyl]-N-hydroxyacetamide.
Claim 10
Dependent Claim
6 words
The monosodium salt of claim 8.
Claim 11
Dependent Claim
8 words
The compound of claim 6 which is N-hydroxy-N-[[2-[[3-(trifluoromethyl)phenyl]amino]phenyl]methyl]acetamide.
Claim 12
Dependent Claim
6 words
The monosodium salt of claim 10.
Claim 13
Dependent Claim
11 words
A compound of claim 6 which is N-hydroxy-N-[[2-[[3-(trifluoromethyl)phenyl]amino]phenyl]methyl]carbamic acid, ethyl ester.
Claim 14
Dependent Claim
8 words
A compound of claim 6 which is N-hydroxy-N'-methyl-N-[[2-[[3-(trifluoromethyl)phenyl]amino]phenyl]methyl]urea.
Claim 15
Dependent Claim
10 words
A compound of claim 6 which is N-[[2-[(2,3-dimethyphenyl)amino]phenyl]methyl]-N-hydroxyacetamide, N-[[2-[(2,6-dichlorophenyl)amino]phenyl]methyl]-N-hydroxyacetamide, N-[1-[2-[(2,6-dichloro-3-methylphenyl)amino]phenyl]ethyl]-N-hydroxyacetamide.
Claim 16
Dependent Claim
23 words
A compound of claim 7 which is [(9H-fluoren-2-ylmethyl)hydroxyamino]oxoacetic acid, N-(9H-fluoren-2-ylmethyl)-N-hydroxyacetamide, [(9H-fluoren-2-ylmethyl)hydroxyamino]oxoacetic acid, ethyl ester, N-(9H-fluoren-2-ylmethyl)-N-hydroxy-2-methylpropanamide, N-(9H-fluoren-2-ylmethyl)-N-hydroxy-N'-methylurea, N-[1-(9H-fluoren-2-yl)ethyl]-N-hydroxy-N'-methylurea, N'-ethyl-N-[1-(9H-fluoren-2-yl)ethyl]-N-hydroxyurea, N-(1-(9H-fluoren-2-yl)ethyl-N-hydroxy-N'-methylthiourea, N-(1-(9H-fluoren-2-yl)ethyl-N-hydroxyacetamide, N-(1-(9H-fluoren-2-yl)ethyl)-N-hydroxy-2-methylpropanamide, or N-(1-(9H-fluoren-2-yl)ethyl)-N-hydroxy-N'-ethylthiourea.
Claim 17
Dependent Claim
5 words
A compound which is N-hydroxy-9H-fluoren-2-methanamine.
Claim 18
Dependent Claim
5 words
A compound which is N-hydroxy-9H-fluoren-2-methanamine.
Claim 19
Dependent Claim
5 words
A compound which is N-hydroxy-α-methyl-9H-fluorene-2-methanamine.
Claim 20
Dependent Claim
5 words
A compound which is N-hydroxy-α-methyl-9H-fluorene-2-methanamine.
Claim 21
Dependent Claim
24 words
A pharmaceutical composition for use as an antiinflammatory agent comprising an antiinflammatory effective amount of the compound of claim 1 and a pharmaceutical carrier.
Claim 22
Dependent Claim
27 words
A method of treating inflammation in a mammal suffering therefrom which comprises administering a therapeutically effective amount of the compound of claim 1 in unit dosage form.
Claim 23
Dependent Claim
50 words
A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 additionally comprising an effective amount of a second active ingredient that is a nonsteroidal antiinflammatory drug; a peripheral analgesic agent; a cyclooxygenase inhibitor; a leukotriene antagonist; an antihistaminic agent; a prostaglandin antagonist or a thromboxane antagonist.
Claim 24
Dependent Claim
24 words
A pharmaceutical composition for use as an antiinflammatory agent comprising an antiinflammatory effective amount of the compound of claim 16 and a pharmaceutical carrier.
Claim 25
Dependent Claim
27 words
A method of treating inflammation in a mammal suffering therefrom which comprises administering a therapeutically effective amount of the compound of claim 17 in unit dosage form.
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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) | 1993-12-31 | 1994-07-02 | 1995-01-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-12-31 | 1998-07-02 | 1999-01-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-12-31 | 2002-07-02 | 2003-01-01 | $7700.00 | Window Closed / Lapsed |