Identification of second-generation P2X3 antagonists for treatment of pain. Issue 8 (1st May 2018)

• Record Type: Journal Article
• Authors: Ginnetti, Anthony T.; Paone, Daniel V.; Stauffer, Shaun R.; Potteiger, Craig M.; Shaw, Anthony W.; Deng, James; Mulhearn, James J.; Nguyen, Diem N.; Segerdell, Carolyn; Anquandah, Juliana; Calamari, Amy; Cheng, Gong; Leitl, Michael D.; Liang, Annie; Moore, Eric; Panigel, Jacqueline; Urban, Mark; Wang, Jixin; Fillgrove, Kerry; Tang, Cuyue; Cook, Sean; Kane, Stefanie; Salvatore, Christopher A.; Graham, Samuel L.; Burgey, Christopher S.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 8(2018)
• Page Start: 1392
• Page End: 1396
• Publication Date: 2018-05-01
• Subjects: P2X3 -- Pain -- UGT1A1 -- Drug-drug interaction -- Purinergic receptor; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.02.039
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: A second-generation small molecule P2X3 receptor antagonist has been developed. The lead optimization strategy to address shortcomings of the first-generation preclinical lead compound is described herein. These studies were directed towards the identification and amelioration of preclinical hepatobiliary findings, reducing potential for drug-drug interactions, and decreasing the projected human dose of the first-generation lead. Abstract: A second-generation small molecule P2X3 receptor antagonist has been developed. The lead optimization strategy to address shortcomings of the first-generation preclinical lead compound is described herein. These studies were directed towards the identification and amelioration of preclinical hepatobiliary findings, reducing potential for drug-drug interactions, and decreasing the projected human dose of the first-generation lead.