Synthesis of 5-chloro-5,8-dideaza analogs of folic acid and aminopterin targeted for colon adenocarcinoma
- 1 August 1987
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 30 (8) , 1515-1519
- https://doi.org/10.1021/jm00391a042
Abstract
Several classical quinazoline analogues of folic acid bearing chloro or methyl substituents at position 5 were evaluated as inhibitors of the growth of four human gastrointestinal adenocarcinoma cell lines in vitro. The preparation of two of these, 5-chloro-5,8-dideazaisofolic acid, 1e, and 5-chloro-5,8-dideazaisoaminopterin, 2a, is reported for the first time. In addition, a new synthetic route to 5-chloro-5,8-dideazaaminopterin, 2b, is described. For compounds having a 2,4-diamino configuration, the presence of chlorine at position 5 afforded superior growth inhibitory potency. However, compound 1e was substantially less effective than its 5-methyl counterpart.This publication has 10 references indexed in Scilit:
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