Synthesis and in vitro antitumor activity of new deaza analogues of the nonpolyglutamatable antifolate N α-(4-amino-4-deoxypteroyl)-N δ-hemiphthaloyl-l-ornithine ( …

CM Vaidya, JE Wright, A Rosowsky

Index: Vaidya, Chitra M.; Wright, Joel E.; Rosowsky, Andre Journal of Medicinal Chemistry, 2002 , vol. 45, # 8 p. 1690 - 1696

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Citation Number: 18

Abstract

Details are disclosed for the synthesis of N α-[4-[2-(2, 4-diaminoquinazolin-6-yl) ethyl] benzoyl]-N δ-hemiphthaloyl-l-ornithine (2) and N α-[4-[5-(2, 4-diaminoteridin-6-yl) pent-1-yn- 4-yl] benzoyl]-N δ-hemiphthaloyl-l-ornithine (6) as analogues of N α-(4-amino-4- deoxypteroyl)-N δ-hemiphthaloyl-l-ornithine (1, PT523), a nonpolyglutamatable antifolate currently in advanced preclinical development. In a 72 h growth inhibition assay against ...