Princeton University

Eli Lilly and Company

Usher III Initiative, Inc.

James M Hamby

Edward C Taylor

Chuan Shih

George P Beardsley

Tracey L Fletcher

Mahdi Farhan

N-[N-(Tetrahydropyrido[2,3-d]pyrimidinylmethyl) aminomethylbenzoyl]glutamic acid derivatives are antineoplastic agents with an effect on one or more enzymes which utilize metabolic derivatives of folic acid. The compounds can be prepared by allowing a protected aminomethylbenzoylglutamic acid derivative to react with 2-amino-4-hydroxy-6-formylpyrido[2,3-d]pyrimidine, reducing the intermediate Schiff base, and subjecting the intermediate to catalytic hydrogenation. A typical embodiment is (S,S) N-[N-(2-amino-4-hydroxy-5,6,7,8- tetrahydropyrido-[2,3-d]pyrimidin-6-ylmethyl)-4-aminomethylbenzoyl]-glutam ic acid.

N-[N-(tetrahydropyrido[2,3-D]pyrimidinylmethyl)-aminomethylbenzo

N-[4-(N'-[2-amino-4(3H)-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-ylme thyl]-N'-acylamino)benzoyl]-L-glutamic acid derivatives are antineoplastic agents. The compounds are prepared through acylation of the corresponding N'-amino compound or hydrolysis of a protected N'-acylamino compound. A typical embodiment is N-[4-(N'-[2-amino-4(3H)-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-6-ylm ethyl]-N'-formylamino)benzoyl]-L-glutamic acid.

4 (3H)-oxo-5,6,7,8-tetrahydropyrido-(2,3-d)pyrimidine derivatives

Growing community of inventors

Plainsboro, NJ, United States of America

James M Hamby