1. Novel phenylpiperazine derivatives as potent transient receptor potential vanilloid 1 antagonists.
- Author
-
Jing L and Liu C
- Subjects
- Animals, Mice, Humans, Pain drug therapy, Structure-Activity Relationship, Male, HEK293 Cells, Rats, TRPV Cation Channels antagonists & inhibitors, TRPV Cation Channels metabolism, Piperazines chemistry, Piperazines pharmacology, Piperazines chemical synthesis, Analgesics pharmacology, Analgesics chemistry, Analgesics chemical synthesis
- Abstract
Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel, which is considered a highly validated target for pain perception. Repeated activation with agonists to desensitize receptors or use the antagonists can both exert analgesic effects. In this work, two series of novel phenylpiperazine derivatives were designed, synthesized, and evaluated for the in vitro receptor inhibitory activity and in vivo analgesic activity. Among them, L-21 containing sulfonylurea group was identified with potent TRPV1 antagonistic activity and analgesic activity in various pain models. At the same time, L-21 exhibited low risk of hyperthermia side effect. These results indicated that L-21 is a promising candidate for further development of novel TRPV1 antagonist to treat pain., (© 2024 John Wiley & Sons Ltd.)
- Published
- 2024
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