Design, synthesis and biological evaluation of novel analgesic agents targeting both cyclooxygenase and TRPV1

Bioorganic & Medicinal Chemistry
Lin YanHai Qian

Abstract

Multitarget-directed ligands might offer certain advantages over traditional single-target drugs and/or drug combinations. In the present study, a series of novel analgesic agents targeting both cyclooxygenase and TRPV1 were prepared and evaluated in an effort to optimize properties of previously described lead compounds from piperazine, ethanediamine cores. These compounds were evaluated for antagonism of hTRPV1 activation by capsaicin and the ability to inhibit Ovine COX-1 and human recombinant COX-2 in vitro. The favorable potentials of these test compounds were further characterized in preliminary analgesic and side-effects tests in vivo. On the basis of comprehensive evaluations, compound 8d which showed strong TRPV1 antagonistic activity, middle COX-2 inhibition, weak ulcerogenic action and had no hyperthermia side-effect was considered as a safe candidate for the further development of analgesic drugs.

Citations

Sep 12, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Smaranda Dafina OnigaCătălin Araniciu
Aug 5, 2017·Future Medicinal Chemistry·Gaganpreet Kaur, Om Silakari
Nov 2, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gwan Ui HongJai Youl Ro
Dec 10, 2020·Heliyon·Ryldene Marques Duarte da CruzReinaldo Nóbrega de Almeida
Jan 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alexandra GyöngyösiIstván Lekli
Aug 7, 2021·Pharmaceuticals·Ryldene Marques Duarte da CruzRicardo Olímpio de Moura

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