The preliminary results on the development of a viable methodology for the further functionalization of 4- hydroxythiazole derivatives to afford target TRPM8 antagonists are reported. The combined Sonogashira coupling/annulation reactions of the ethyl 2-(3-fluorophenyl)-4-tifluoromethylsulfonyloxy-1,3-thiazole-5- carboxylate have been applied to the synthesis of analogues of the selective blocker of TRPM8 DFL23448. Among all the synthetised derivatives, the most promising compound resulted to be active as TRPM8 blocker (IC50 = 4.06 μM), showing an excellent metabolic stability and no cytotoxic effects. Finally, in silico characterisation of the derivatives showed no violation of the drug-likeness rules.

Design, synthesis and biological evaluation of new thiazole scaffolds as potential TRPM8 antagonists.

Vincenzo Marsicano
Membro del Collaboration Group
;
Antonio Arcadi
;
2021

Abstract

The preliminary results on the development of a viable methodology for the further functionalization of 4- hydroxythiazole derivatives to afford target TRPM8 antagonists are reported. The combined Sonogashira coupling/annulation reactions of the ethyl 2-(3-fluorophenyl)-4-tifluoromethylsulfonyloxy-1,3-thiazole-5- carboxylate have been applied to the synthesis of analogues of the selective blocker of TRPM8 DFL23448. Among all the synthetised derivatives, the most promising compound resulted to be active as TRPM8 blocker (IC50 = 4.06 μM), showing an excellent metabolic stability and no cytotoxic effects. Finally, in silico characterisation of the derivatives showed no violation of the drug-likeness rules.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11697/174265
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