Folate antagonists. 20. Synthesis and antitumor and antimalarial properties of trimetrexate and related 6-[(phenylamino)methyl]-2,4-quinazolinediamines
- 1 December 1983
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 26 (12), 1753-1760
- https://doi.org/10.1021/jm00366a018
Abstract
A series of 6-[(arylamino)methyl]-2,4-quinazolinediamines was prepared by catalytic hydrogenation of the requisite 2,4-diamino-6-quinazolinecarbonitriles in the presence of the appropriate benzenamine. Formylation, acetylation and nitrosation provided N.omega. derivatives of these compounds. A variety of the compounds exhibited potent antimalarial, antibacterial and antitumor activity. 5-Methyl-6-[[(3,4,5-trimethoxyphenyl)amino]methyl]-2,4-quinazolinediamine (trimetrexate) showed broad spectrum antitumor effects and is undergoing preclinical toxicology evaluation prior to trial in man.This publication has 5 references indexed in Scilit:
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