US4883799A
Expired / Lapsed
US
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N-(4-(1-hydroxy-3-(5,6,7,8-tetrahydropyrido(2,3,-d)-pyrimidin-6-yl)prop-2-yl)benzoyl)glutamic acid derivatives
Assignee: Princeton University
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Filing: 1988-06-29
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Granted: 1989-11-28
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Expires: 2008-06-29
Abstract
Abstract N-[4-{1-Hydroxy-3-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)prop-2-yl )benzoyl]-glutamic acid, it salts, and derivatives thereof, have an inhibitory effect on one or more enzymes which utilize folic acid and can be used, alone or in combination, to inhibit the growth of those neoplasms which otherwise depend upon the enzymes so inhibited. The compounds can be prepared through catalytic hydrogenation of a protected derivative of N-[4-{1-hydroxy-3-(2-amino-4-hydroxy-pyrido[2,3-d]pyrimidin-6-yl)prop-2-en-2-yl)benzoyl]glutamic acid and removal of the protecting groups.
Inventors
- 👤 Edward C. Taylor
- 👤 Cheol-min Yoon
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 19:17
CPC Classifications
C; C07; C07D; C07D487/00; C07D487/02; C07D487/04; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55; Y02P20/582
Claims Analysis
Total Claims: 8
Claim 1
Independent Claim
47 words
A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR7## in which the configuration about the carbon atoms designated C* is (R) or (S), and the configuration about the carbon atom designated C** is (S); and the pharmaceutically acceptable salts thereof.
Claim 2
Dependent Claim
47 words
A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR7## in which the configuration about the carbon atoms designated C* is (R) or (S), and the configuration about the carbon atom designated C** is (S); and the pharmaceutically acceptable salts thereof.
Claim 3
Dependent Claim
14 words
A compound according to claim 1 wherein said glutamic acid derivative is N-[4-{1-hydroxy-3-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl)prop-2-yl}benzoyl]glutamic acid.
Claim 4
Dependent Claim
11 words
The disodium salt of the glutamic acid derivative of claim 2.
Claim 5
Dependent Claim
49 words
The method of inhibiting neoplastic growth in a mammal which growth is dependent on folic acid or a metabolic derivative of folic acid as a substrate, which comprises administering to the mammal in a single or multiple dose regimen an effective amount of a compound according to claim 1.
Claim 6
Dependent Claim
64 words
A pharmaceutical composition for inhibiting neoplastic growth in a mammal which growth is dependent on folic acid or a metabolic derivative of folic acid as a substrate, which comprises an amount of a compound according to claim 1 which upon administration to the mammal in a single or multiple dose regimen is effective to inhibit said growth, in combination with a pharmaceutically acceptable carrier.
Claim 7
Dependent Claim
174 words
A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR8## in which: R 1 is --OH or --NH 2 ; R 2 is hydrogen or a carboxy protecting group selected from the group consisting of (a) a straight or branched lower alkyl ester which is unsubstituted or substituted in the 1- or 2-position with (i) lower alkoxy, (ii) lower alkylthio, (iii) halogen, (iv) phenyl which is unsubstituted or mono-, di- or tri-substituted with lower alkyl, lower alkoxy, hydroxy, halo, or nitro, or (v) aroyl, or (b) a silyl group; R 3 is hydrogen or a hydroxy protecting group selected from the group consisting of an acetal and a ketal; R 4 is hydrogen or an unsubstituted or substituted acyl amino protecting group; at least one of R 2 , R 3 , and R 4 being other than hydrogen; the configuration about the carbon atoms designated C* is (R) or (S), and the configuration about the carbon atom designated C** is (S); and the pharmaceutically acceptable salts thereof.
Claim 8
Dependent Claim
174 words
A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR8## in which: R 1 is --OH or --NH 2 ; R 2 is hydrogen or a carboxy protecting group selected from the group consisting of (a) a straight or branched lower alkyl ester which is unsubstituted or substituted in the 1- or 2-position with (i) lower alkoxy, (ii) lower alkylthio, (iii) halogen, (iv) phenyl which is unsubstituted or mono-, di- or tri-substituted with lower alkyl, lower alkoxy, hydroxy, halo, or nitro, or (v) aroyl, or (b) a silyl group; R 3 is hydrogen or a hydroxy protecting group selected from the group consisting of an acetal and a ketal; R 4 is hydrogen or an unsubstituted or substituted acyl amino protecting group; at least one of R 2 , R 3 , and R 4 being other than hydrogen; the configuration about the carbon atoms designated C* is (R) or (S), and the configuration about the carbon atom designated C** is (S); and the pharmaceutically acceptable salts thereof.
References Cited (Backward Citations)
US4684653A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-11-27 | 1993-05-29 | 1993-11-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-11-27 | 1997-05-29 | 1997-11-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-11-27 | 2001-05-29 | 2001-11-28 | $7700.00 | Window Closed / Lapsed |