Synthesis and antifolate evaluation of the 10-propargyl derivatives of 5-deazafolic acid, 5-deazaaminopterin, and 5-methyl-5-deazaaminopterin

JR Piper, ND Malik, MS Rhee, J Galivan…

Index: Piper, J. R.; Malik, N. D.; Rhee, M. S.; Galivan, J.; Sirotnak, F. M. Journal of Medicinal Chemistry, 1992 , vol. 35, # 2 p. 332 - 337

Full Text: HTML

Citation Number: 15

Abstract

Both 12a and ita 5-methyl-substituted analogue 12b were converted to versatile 6bromomethyl intermediates 13a and 13b from which important antifolates may be readily derived. Alkylation of 7 by 13a, b led to 10-propargyl-5-deazaaminopterin (5) and 5-methy1- 10-propargy1-5-deamaminopterin (6). As an inhibitor of TS from H% F/F cells, 4 gave an ICso value Mhowing it to be approximately 6-fold lese inhibitory than PDDF (90 nM for 4 ...