Bicyclic cytarabine analogues: synthesis and investigation of antitumor properties of novel, 6-aryl- and 6-alkyl-3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one arabinosides

Abstract

A series of sixteen hitherto unknown Cytarabine analogues bearing a bicyclic 3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one base modified with aryl, pyridyl, benzyl and alkyl substituents was prepared in a straightforward approach. This is the one of the few examples of the synthesis of pyrrolo[2,3-d]pyrimidin-2(7H)-one nucleosides and the first example of pyrrolo[2,3-d]pyrimidin-2(7H)-one nucleosides possessing arabinose moiety. For the first time, the conversion of the furopyrimidine arabinoside products to a series of novel pyrrolopyrimidines by ammonolysis reaction was thoroughly investigated using aqueous and methanolic reaction conditions under classical and micro-wave heating. This approach resulted in a small library of compounds, which were evaluated for their antiproliferative properties against HL-60 and Jurkat E6.1 cell lines. All synthesized compounds exhibited a weaker cytotoxic effect in comparison to the mother compound. Of all the tested compounds, the derivative bearing a 4-n-pentylphenyl substituent exhibited the highest antiproliferative activity.