2005

Pyrimidine derivativesR 0510 Antileishmanial Agents. Part 4. Synthesis and Antileishmanial Activity of Novel

Terpenyl Pyrimidines. — In order to avoid the environmentally benign methodology enabling access to oxygen-substituted terpenyl pyrimidines, the keto ester (III) is visu-alized as a key synthon to extend it to the desired diaminopyrimidines. Classical con-densation of (III) with pre-prepared guanidine (IV) furnishes pyrimidone (V) only in moderate yield. Attempts to improve the yield of (V) fail. However, initial problems with regard to the preparation of chloride (VI) are circumvented by the reaction of (V) with POCl3. Having achieved the synthesis of (VI) on a comfortable scale, it is used for the synthesis of a library of diamino pyrimidines (VIII) and oxygen-substituted pyrim-idines (X). Compounds (VIII) and (X) are screened for in vitro antileishmanial activity in the promastigote model and display 100% inhibition at 10 µg ml-1 concentration. — (CHANDRA, N.; RAMESH; ASHUTOSH; GOYAL, N.; SURYAWANSHI*, S. N.; GUPTA, S.; Eur. J. Med. Chem. 40 (2005) 6, 552-556; Div. Med. Chem., Cent. Drug Res. Inst., Lucknow 226 001, India; Eng.) — H. Hoennerscheid

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