US4882334A
Expired / Lapsed
US
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N-(5,6,7,8-tetrahydropyrido]2,3-d]pyrimidin-6-ylethl-thineyl-and furylcarbonyl)-glutamic acid derivatives
Assignee: Eli Lilly and Co
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Filing: 1988-05-25
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Granted: 1989-11-21
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Expires: 2008-05-25
Abstract
Abstract N-(Thienylcarbonyl)glutamic acid and N-(furylcarbonyl)glutamic acid derivatives in which the thienyl or furyl group is substituted with the 2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-ylethyl or 2,4-diamino-5,6,7,8-tetrahydropyrido[2,3-d]-pyrimidin-6-ylethyl group are antineoplastic agents. Typical embodiments are N-[5-(2-{2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl}ethyl)thien-2-ylcarbonyl]-L-glutamic acid and N-[5-(2-{2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl}ethyl)fur-2-ylcarbony]-L-glutamic acid.
Inventors
- 👤 Chuan Shih
- 👤 Edward C. Taylor
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-24 13:26
CPC Classifications
C; C07; C07D; C07D471/00; C07D471/02; C07D471/04
Claims Analysis
Total Claims: 11
Claim 1
Independent Claim
54 words
A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR7## in which: Q is --O-- or --S--; R 1 is --OH or --NH 2 ; R 3 is hydrogen, chloro, or fluoro; the configuration about the carbon atom designated * is S; and the pharmaceutically acceptable salts thereof.
Claim 2
Dependent Claim
54 words
A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR7## in which: Q is --O-- or --S--; R 1 is --OH or --NH 2 ; R 3 is hydrogen, chloro, or fluoro; the configuration about the carbon atom designated * is S; and the pharmaceutically acceptable salts thereof.
Claim 3
Dependent Claim
11 words
A compound according to claim 1 wherein R 1 is --OH.
Claim 4
Dependent Claim
10 words
A compound according to claim 2 wherein Q is --S--.
Claim 5
Dependent Claim
13 words
A compound according to claim 3 which is (S,S)-N-[5-(2-{2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl}ethyl)thien-2-ylcarbonyl]-L-glutamic acid or (R,S)-N-[5-(2-{2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl{ethyl)thien-2-ylcarbonyl]-L-glutamic acid.
Claim 6
Dependent Claim
10 words
A compound according to claim 2 wherein Q is --O--.
Claim 7
Dependent Claim
13 words
A compound according to claim 5 which is (S,S)-N-[5-(2-{2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl}ethyl)fur-2-ylcarbonyl]-L-glutamic acid or (R,S)-N-[5-(2-{2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl}ethyl)fur-2-ylcarbonyl]-L-glutamic acid.
Claim 8
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 9
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 10
Dependent Claim
144 words
A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR8## in which: Q is --O-- or --S--; 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, chloro, or fluoro; R 4 is hydrogen or an unsubstituted or substituted acyl amino protecting group; at least one of R 2 and R 4 being other than hydrogen; and the configuration about the carbon atom designated * is S.
Claim 11
Dependent Claim
144 words
A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR8## in which: Q is --O-- or --S--; 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, chloro, or fluoro; R 4 is hydrogen or an unsubstituted or substituted acyl amino protecting group; at least one of R 2 and R 4 being other than hydrogen; and the configuration about the carbon atom designated * is S.
References Cited (Backward Citations)
US4684653A
Cited
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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) | 1992-11-20 | 1993-05-22 | 1993-11-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-11-20 | 1997-05-22 | 1997-11-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-11-20 | 2001-05-22 | 2001-11-21 | $7700.00 | Window Closed / Lapsed |