Nitrogen containing heterocyclic compounds are important structural motifs of several biologically active natural products and, thus, attracted immense research interest in medicinal chemistry including novel therapeutic molecules for cancer therapy. Prostate cancer is one of the most common types of cancer in men and second most leading cause of death in USA. Inhibition of tubulin polymerization has emerged as novel strategy against prostate cancer. Out of various N-heterocycles, pyrazole has been used as scaffolds for synthesis of various drugs and similarity with molecular building blocks for tubulin polymerization, makes them good candidates for synthesizing new drug molecules for prostate cancer therapy. Development of an effective protocol for the regioselective synthesis of such substituted pyrazoles via the oxidative C-H functionalization would be of great interest in organic synthesis and producing effective prostate cancer drugs. Here, we report the synthesis of trisubstituted pyrazoles via C-H cross-dehydrogenative coupling of alkenyl hydrazone using copper triflate as a catalyst. Mild reaction condition and moderate yields are the practical features of this protocol in producing six pyrazole based compounds (Scheme 1). Tubulin polymerization assay showed their efficiency in inhibition and in vitro studies could establish their effect in inhibiting prostate cell line hTERT PF179T CAF at a low micromolar concentration.

Synthesis of functionalized pyrazoles via copper-catalyzed C-N dehydrogenative cross-coupling for prostate cancer therapy by inhibiting tubulin polymerization

255th National Meeting (2018)

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