Synthesis and antifolate properties of 10-alkyl-8,10-dideazaminopterins
- 1 March 1984
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 27 (3) , 376-380
- https://doi.org/10.1021/jm00369a024
Abstract
The synthesis of 10-alkyl analogs of the potent antitumor agent 8,10-dideazaminopterin is described. Alkylation of appropriate .alpha.-allkyl homoterephthalate esters with 2,4-diamino-6-(bromomethyl)-8-deazapteridine afforded 10-alkyl-10-carboxy-4-amino-4-deoxy-8,10-dideazapteroic acid diesters. Ester cleavage and decarboxylation at C-10 were accomplished by heating with sodium cyanide in Me2SO at 170-180.degree. C to afford the 2,4-diamino-10-alkyl-8,10-dideazapteroic acids. The acids were coupled with diethyl glutamate, followed by saponification, to give the 10-alkyl-8,10-dideazaminopterins. The compounds were potent inhibitors of growth in folate-dependent bacteria, Streptococcus faecium and Lactobacillus casei. The 10-methyl and 10-ethyl analogs gave the highest percent increases in life span [ILS] for mice infected with L1210 leukemia with ILS values of +203 and +235%, respectively.This publication has 3 references indexed in Scilit:
- Synthesis and antitumor activity of 10-alkyl-10-deazaminopterins. A convenient synthesis of 10-deazaminopterinJournal of Medicinal Chemistry, 1982
- Pyridopyrimidines. 12. Synthesis of 8-deaza analogs of aminopterin and folic acidThe Journal of Organic Chemistry, 1981
- Synthesis and antifolate activity of 10-deazaminopterinJournal of Medicinal Chemistry, 1974