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

• Published in: Tetrahedron Vol. 53; no. 39; pp. 13383 - 13396
• Main Authors: Bavetsias, Vassilios, Bisset, Graham M.F., Kimbell, Rosemary, Boyle, F.Thomas, Jackman, Ann L.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 29.09.1997; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; LINKED DIPEPTIDE; PEPTIDES; INVITRO; CB3717; L1210; DIPEPTIDE ANALOGS; DERIVATIVES; 2-DESAMINO-2-METHYL-N-10-PROPARGYL-5,8-DIDEAZAFOLIC ACID ICI-198583

Several novel antifolates, derivatives of 2-desamino-2-methyl- N 10-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-OB...