US4412994A
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Mannich-base hydroxamic acid prodrugs, compositions and use
Assignee: Interx Research Corp
•
Filing: 1982-05-28
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Granted: 1983-11-01
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Expires: 2002-05-28
Abstract
Abstract Novel prodrug forms of known non-steroidal anti-inflammatory agents are disclosed, said prodrugs having the structural formula ##STR1##
Inventors
- 👤 Kenneth B. Sloan
- 👤 Roy Little
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 04:48
CPC Classifications
C; C07; C07D; C07D295/00; C07D295/04; C07D295/12; C07D295/125; C07D295/13; C07D209/00; C07D209/02; C07D209/04; C07D209/10; C07D209/18; C07D209/26; C07D209/28
Claims Analysis
Total Claims: 35
Claim 1
Independent Claim
146 words
A compound of the formula ##STR161## wherein ##STR162## is the acyl residue of indomethacin; R 1 and R 2 , which can be the same or different, each represent a member selected from the hydrocarbon group consisting of alkyl of 1 to 20 carbon atoms; alkenyl or 2 to 20 carbon atoms; aryl or 6 to 10 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; cycloalkenyl of 4 to 8 carbon atoms; alkynyl of 2 to 20 carbon atoms; aralkyl, alkaryl, aralkenyl, aralkynyl, alkenylaryl, and alkynylaryl, wherein the alkyl, alkenyl, alkynyl, and aryl portions are defined as above; or R 1 and R 2 are combined so that --NR 1 R 2 together represent the residue of a saturated heterocyclic compound containing one secondary nitrogen atom; R 3 is hydrogen or R 1 ; or a non-toxic pharmaceutically acceptable acid addition salt or oxide thereof.
Claim 2
Dependent Claim
146 words
A compound of the formula ##STR161## wherein ##STR162## is the acyl residue of indomethacin; R 1 and R 2 , which can be the same or different, each represent a member selected from the hydrocarbon group consisting of alkyl of 1 to 20 carbon atoms; alkenyl or 2 to 20 carbon atoms; aryl or 6 to 10 carbon atoms; cycloalkyl of 3 to 8 carbon atoms; cycloalkenyl of 4 to 8 carbon atoms; alkynyl of 2 to 20 carbon atoms; aralkyl, alkaryl, aralkenyl, aralkynyl, alkenylaryl, and alkynylaryl, wherein the alkyl, alkenyl, alkynyl, and aryl portions are defined as above; or R 1 and R 2 are combined so that --NR 1 R 2 together represent the residue of a saturated heterocyclic compound containing one secondary nitrogen atom; R 3 is hydrogen or R 1 ; or a non-toxic pharmaceutically acceptable acid addition salt or oxide thereof.
Claim 3
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is alkyl.
Claim 4
Dependent Claim
22 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is C 1 -C 8 alkyl.
Claim 5
Dependent Claim
15 words
A compound according to claim 1 wherein R 1 and R 2 are each alkyl.
Claim 6
Dependent Claim
19 words
A compound according to claim 1 wherein R 1 and R 2 are each C 1 -C 8 alkyl.
Claim 7
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is alkenyl.
Claim 8
Dependent Claim
22 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is C 2 -C 8 alkenyl.
Claim 9
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is aryl.
Claim 10
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is cycloalkyl.
Claim 11
Dependent Claim
22 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is C 5 -C 6 cycloalkyl.
Claim 12
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is cycloalkenyl.
Claim 13
Dependent Claim
22 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is C 5 -C 6 cycloalkenyl.
Claim 14
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is alkynyl.
Claim 15
Dependent Claim
22 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is C 2 -C 8 alkynyl.
Claim 16
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is aralkyl.
Claim 17
Dependent Claim
20 words
A compound according to claim 15 wherein the alkyl portion of the aralkyl radical contains 1 to 6 carbon atoms.
Claim 18
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is alkaryl.
Claim 19
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is aralkenyl.
Claim 20
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is aralkynyl.
Claim 21
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is alkenylaryl.
Claim 22
Dependent Claim
18 words
A compound according to claim 1 wherein at least one of R 1 and R 2 is alkynylaryl.
Claim 23
Dependent Claim
34 words
A compound according to claim 1 wherein R 1 and R 2 are combined so that --NR 1 R 2 together represent the residue of a saturated heterocyclic compound containing one secondary nitrogen atom.
Claim 24
Dependent Claim
35 words
A compound according to claim 22 wherein the residue is that of a saturated monocycle containing one or more hetero atoms in the ring and optionally bearing one or more phenyl, benzyl or methyl substituents.
Claim 25
Dependent Claim
28 words
A compound according to claim 23 wherein the residue is selected from the group consisting of morpholino, 1-pyrrolidinyl, 4-benzyl-1-piperazinyl, 4-methyl-1-piperazinyl, piperidino, hexamethyleneimino, 4-phenylpiperidino, 2-methyl-1-pyrazolidinyl, 3-methyl-1-imidazolidinyl, 4-benzylpiperidino and 4-phenyl-1-piperazinyl.
Claim 26
Dependent Claim
11 words
A compound according to claim 1 wherein R 3 is hydrogen.
Claim 27
Dependent Claim
13 words
A compound according to claim 1 wherein R 3 is R 1 .
Claim 28
Dependent Claim
13 words
A compound according to claim 26 wherein R 1 is an alkyl radical.
Claim 29
Dependent Claim
10 words
The compound according to claim 1 which is α-[1-(4'-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-(morpholinomethyl)acetohydroxamic acid.
Claim 30
Dependent Claim
10 words
The compound according to claim 1 which is α-[1-(4'-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-(N',N'-diethylaminomethyl)acetohydroxamic acid.
Claim 31
Dependent Claim
10 words
The compound according to claim 1 which is α-[1-(4'-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-[(4-methylpiperazin-1-yl)methyl]acetohydroxamic acid.
Claim 32
Dependent Claim
29 words
The compound according to claim 1 which is selected from the group consisting of: α-[1-(4'-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-(piperidinomethyl)acetohydroxamic acid; α-[1-(4'-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-[(pyrrolidin-1-yl)methyl]acetohydroxamic acid; α-[1-(4'-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-(N',N'-dicyclohexylaminomethyl)acetohydroxamic acid; α-[1-(4'-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-(N',N'-dimethylaminomethyl)acetohydroxamic acid; α-[1-(4'-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-(N',N'-diisopropylaminomethyl)acetohydroxamic acid; α-[1-(4'-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-(N',N'-dipentylaminomethyl)acetohydroxamic acid; and α-[1-(4'-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl]-N-(N',N'-dioctylaminomethyl)acetohydroxamic acid.
Claim 33
Dependent Claim
26 words
A pharmaceutical composition of matter comprising an anti-inflammatory effective amount of a compound of claim 1, in combination with a nontoxic pharmaceutically acceptable inert carrier therefor.
Claim 34
Dependent Claim
31 words
A method for alleviating inflammation in or on a warm-blooded animal exhibiting an inflammatory response, which comprises administering thereto an anti-inflammatory effective amount of a compound as claimed in claim 1.
Claim 35
Dependent Claim
31 words
A method for alleviating inflammation in or on a warm-blooded animal exhibiting an inflammatory response, which comprises administering thereto an anti-inflammatory effective amount of a composition as claimed in claim 32.
References Cited (Backward Citations)
No citation records indexed.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1986-10-31 | 1987-05-02 | 1987-11-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-10-31 | 1991-05-02 | 1991-11-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-10-31 | 1995-05-02 | 1995-11-01 | $7700.00 | Window Closed / Lapsed |