Synthesis of novel quinazoline-based antifolates with modified glutamate side chains as potential inhibitors of thymidylate synthase and antitumour agents

V Bavetsias, GMF Bisset, R Kimbell, FT Boyle…

Index: Bavetsias, Vassilios; Bisset, Graham M. F.; Kimbell, Rosemary; Boyle, F. Thomas; Jackman, Ann L. Tetrahedron, 1997 , vol. 53, # 39 p. 13383 - 13396

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Citation Number: 15

Abstract

Several novel antifolates, derivatives of 2-desamino-2-methyl-N10-propargyl-5, 8- dideazafolic acid, were synthesised as inhibitors of thymidylate synthase (TS) and antitumour agents. This was accomplished by first developing routes to the key intermediates Glu-Ome-γ-ψ [CSNH] Glu (OEt)-OEt (8), Glu-OBut-γ-ψ [CH2NH] Glu (OBut)- OBut (16), Glu-OMe-γ-ψ [CN4] Gly-OMe (23) and its 2, 5-disubstituted regioisomer (22), ...