Quinazoline antifolates inhibiting thymidylate synthase: 2-desamino derivatives with enhanced solubility and potency

…, TJ Thornton, A Flinn, AL Jackman…

Index: Jones; Thornton; Flinn; Jackman; Newell; Calvert Journal of Medicinal Chemistry, 1989 , vol. 32, # 4 p. 847 - 852

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Citation Number: 70

Abstract

The poor solubility of the thymidylate synthase (TS) inhibiting antifolate lO-propargy1-5, 8- dideazafolic acid has posed problems for its clinical use and is probably responsible for its renal toxicity. The insolubility is caused by the 2-amino-3, Cdihydro-Coxopyrimidine moiety of the drug which stabilizes the solid state by intermolecular hydrogen bonding. In examining this moiety we have removed the 2-amino group and now report on 2- ...