Synthetic, Structural, and Anticancer Activity Evaluation Studies on Novel Pyrazolylnucleosides

Yadav, Yogesh; Sharma, Deepti; Kaushik, Kumar; Kumar, Vineet; Jha, Amitabh; Prasad, Ashok K.; Len, Christophe; Malhotra, Sanjay V.; Wengel, Jesper; Parmar, Virinder S.

In our approach, the synthesis of the target compounds 5a-e and 6a-e was achieved in two steps starting from the already reported 3-cyanomethyl-5-aryl-1H-pyrazoles 1a-e [44] and the well-known 2-deoxy-3,5-di-O-p-toluoyl-α-D-ribofuranosyl chloride (2) [45] (Scheme 1). Treatment of pyrazoles 1a-e with sodium hydride in acetonitrile and the subsequent addition of chlorosugar 2 gave two regioisomers of the modified pyrazolyl nucleosides 3a-e (by coupling 2 with the N-1 nitrogen of the pyrazole derivatives) and 4a-e (by coupling chlorosugar 2 with the N-2 nitrogen of the pyrazole derivatives) in 58-65% yields. The products 3a-e and 4a-e were de-toluoylated by Despite the developments in nucleoside chemistry, the clinical use of nucleosides has some drawbacks due to their side-effects and primary or acquired drug resistance [43] . Therefore, the search for the design of new and effective nucleoside-based analogues continues to motivate studies in this field. Our efforts toward this goal have led to the synthesis of twenty novel pyrazolylnucleosides with new structures and potent antiviral and antitumoral behaviors. In this regard, two regioisomers for each pyrazole derivative have been produced and characterized using spectroscopic techniques such as 1 H NMR, 13 C NMR, NOESY, HMBC, IR, and mass spectroscopy. All compounds were evaluated against the National Cancer Institute (NCI)'s panel of 60 human tumor cell lines for their anticancer activities, and for their antiviral activities against representative viruses.