N-(5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-yl-alkanoyl)-glutamic acid derivatives

Claim 2

A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR9## in which: R 1 is --OH or --NH 2 ; R 3 is a carbon-carbon bond, alkylene of 1 to 4 carbon atoms, or cyclohexylene; the configuration about the carbon atom designated * is S; and the pharmaceutically acceptable salts thereof.

Claim 3

A compound according to claim 1 wherein R 1 is --OH.

Claim 4

A compound according to claim 2 wherein R 3 is a carbon-carbon bond, methylene, ethylene, trimethylene, or tetramethylene.

Claim 5

A compound according to claim 3 which is (S,S)-N-[3-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]-pyrimidin-6-yl)propioyl]-L-glutamic acid or (R,S)-N-[3-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido-[2,3-d]pyrimidin-6-yl)propioyl]-L-glutamic acid.

Claim 6

A compound according to claim 3 which is (S,S)-N-[4-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]-pyrimidin-6-yl)butyryl]-L-glutamic acid or (R,S)-N-[4-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido-[2,3-d]pyrimidin-6-yl)butyryl]-L-glutamic acid.

Claim 7

A compound according to claim 3 which is (S,S)-N-[5-(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]-pyrimidin-6-yl)pentanoyl]-L-glutamic acid or (R,S)-N-[5-(2-amino-5-hydroxy-5,6,7,8-tetrahydropyrido-[2,3-d]pyrimidin-6-yl)pentanoyl]-L-glutamic acid.

Claim 8

A compound according to claim 3 which is (S,S)-N-[6(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]-pyrimidin-6-yl)hexanoyl]-L-glutamic acid or (R,S)-N[6-(2-amino-6-hydroxy-5,6,7,8-tetrahydropyrido-[2,3-d]pyrimidin-6-yl)hexanoyl]-L-glutamic acid.

Claim 9

A compound according to claim 3 which is (S,S)-N-[7(2-amino-4-hydroxy-5,6,7,8-tetrahydropyrido[2,3-d]-pyrimidin-6-yl)heptanoyl]-L-glutamic acid or (R,S)-N-[7-(2-amino-6-hydroxy-5,6,7,8-tetrahydropyrido-[2,3-d]pyrimidin-6-yl)heptanoyl]-L-glutamic acid.

Claim 10

A compound according to claim 2 wherein R 3 is 1,4-cyclohexylene.

Claim 11

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 12

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 13

A pharmaceutical composition for combatting neoplastic growth in a mammal 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 combat said growth, in combination with a pharmaceutically acceptable carrier.

Claim 14

A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR10## 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 a carbon-carbon bond, alkylene of 1 to 4 carbon atoms, or cyclohexylene; 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[; and the pharmaceutically acceptable salts thereof.

Claim 15

A compound selected from the group consisting of a glutamic acid derivative having the formula: ##STR10## 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 a carbon-carbon bond, alkylene of 1 to 4 carbon atoms, or cyclohexylene; 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[; and the pharmaceutically acceptable salts thereof.