title: Folate antagonists. 20. Synthesis and antitumor and antimalarial properties of trimetrexate and related 6-[(phenylamino)methyl]-2,4-quinazolinediamines.
abstract: A series of 6-[(arylamino)methyl]-2,4-quinazolinediamines have been 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. In particular, 5-methyl-6-[[(3,4,5-trimethoxyphenyl)-amino]methyl]-2, 4-quinazolinediamine (trimetrexate, 15) has shown a broad spectrum of antitumor effects and is undergoing preclinical toxicology evaluation prior to trial in man.
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis*; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001419:Bacteria / Q000187:drug effects; D004351:Drug Resistance; D005493:Folic Acid Antagonists / Q000138:chemical synthesis*; D000882:Haplorhini; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000627:therapeutic use; D016597:Trimetrexate
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D011799:Quinazolines; D016597:Trimetrexate