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1. Pyrrolinone derivatives as a new class of P2X3 receptor antagonists. Part 1: Initial structure-activity relationship studies of a hit from a high throughput screening.

Author

Tobinaga H, Kameyama T, Oohara M, Kobayashi N, Ohdan M, Ishizuka N, Kume M, Tomari M, Tanaka Y, Takahashi F, Kinoshita H, Shimada S, Shinohara S, and Kai H

Subjects
Analgesics chemical synthesis, Analgesics chemistry, Animals, Cell Line, Tumor, High-Throughput Screening Assays, Molecular Structure, Purinergic P2X Receptor Antagonists chemical synthesis, Purinergic P2X Receptor Antagonists chemistry, Pyrroles chemical synthesis, Pyrroles chemistry, Rats, Structure-Activity Relationship, Analgesics pharmacology, Purinergic P2X Receptor Antagonists pharmacology, Pyrroles pharmacology
Abstract

The P2X3 receptor is primarily expressed in the peripheral sensory nerves, and therefore, antagonists of this receptor may be useful for the treatment of chronic pain. Pyrrolinone derivatives have been identified as a novel class of P2X3 receptor antagonists. A lead structure with moderate activity was discovered through a high-throughput screening assay. A structure-activity study led to the discovery of several P2X3 receptor antagonists. Compound 34 showed potent and specific antagonistic activity and analgesic efficacy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Published
2018
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