Bae, Jinsu published the artcileSynthesis and Structure-Activity Relationship Studies of Benzimidazole-4,7-dione-Based P2X3 Receptor Antagonists as Novel Anti-Nociceptive Agents, Computed Properties of 73874-95-0, the main research area is neuropathic pain antinociceptive structure activity relationship; P2X3 receptor; adenosine 5′-triphosphate; antagonist; anti-nociceptive agents; neuropathic pain; structure−activity relationship study.
P2X3 receptors (P2X3R) are ATP-gated ion channels predominantly expressed in C- and Aδ-fiber primary afferent neurons and have been introduced as a novel therapeutic target for neurol. disorders, including neuropathic pain and chronic cough. Because of its localized distribution, antagonism of P2X3R has been thoroughly considered, and the avoidance of issues related to CNS side effects has been proven in clin. trials. In this article, benzimidazole-4,7-dione-based derivatives were introduced as a new chem. entity for the development of P2X3R antagonists. Starting from the discovery of a hit compound from the screening of 8364 random library compounds in the Korea Chem. Bank, which had an IC50 value of 1030 nM, studies of structure-activity and structure-property relationships enabled further optimization toward improving the antagonistic activities as well as the drug′s physicochem. properties, including metabolic stability. As for the results, the final optimized compound 14h was developed with an IC50 value of 375 nM at P2X3R with more than 23-fold selectivity vs. P2X2/3R, along with properties of metabolic stability and improved solubility In neuropathic pain animal models evoked by either nerve ligation or chemotherapeutics in male Sprague-Dawley rats, compound 14h showed anti-nociceptive effects through an increase in the mech. withdrawal threshold as measured by von Frey filament following i.v. administration.
Molecules published new progress about Analgesics. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Computed Properties of 73874-95-0.
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem