期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 24, 期 4, 页码 849-857出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2016.01.009
关键词
Analgesic; Transient receptor potential vanilloid type 1; Cyclooxygenase; Hyperthermia
资金
- National Natural Science Foundation of China [81273376, 21202034]
- Natural Science Foundation of Jiangsu Province of China [BK2012759]
- Scientific and Technological Project of Henan Province
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. (c) 2016 Elsevier Ltd. All rights reserved.
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