European journal of medicinal chemistry

Structural variations of piritrexim, a lipophilic inhibitor of human dihydrofolate reductase: synthesis, antitumor activity and molecular modeling investigations

M Zink, H Lanig, R Troschütz

Index: Zink, Mario; Lanig, Harald; Troschuetz, Reinhard European Journal of Medicinal Chemistry, 2004 , vol. 39, # 12 p. 1079 - 1088

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Citation Number: 35

Abstract

Piritrexim (PTX)(1), a lipophilic inhibitor of the human dihydrofolate reductase, has been evaluated as an anticancer agent. The synthesis of four structural variations (2–5) of PTX is reported. The PTX analogues 2–5 were obtained by reaction of suitable C3-building blocks with pyrimidine-2, 4, 6-triamine (14) or with cyanacetamide (7) and guanidine (10). The evaluation of 2–4 for antitumor activity against a panel of 60 human cancer cell lines ...