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■ Synthesis of Pyrrolo[2,3-d]pyrimidine Analogues: “Pyridine Ring” Analogues of Pemetrexed

Yun Xu, Mingfeng Yu, Yan Long, Han Wu, and Zhenmin Mao*

*School of Pharmacy, Shanghai Jiaotong University , 800 Dongchuan Road, Shanghai 200240, China

Abstract

Two analogues of pemetrexed with its phenyl ring replaced with pyridine ring as novel anticancer agents were synthesized. Preliminary in vitro evaluation indicated that replacement of the phenyl moiety of pemetrexed by the pyridine ring with the 6-5 bicyclic ring system showed low cytotoxicity, that departs from the findings with antifolates bearing 6-6 bicyclic ring system.