Cover Picture: Discovery of Novel Potent Muscarinic M3 Receptor Antagonists with Proper Plasma Stability by Structural Recombination of Marketed M3 Antagonists (ChemMedChem 15/2017). (8th August 2017)

• Record Type: Journal Article
• Authors: Xiang, Zuojuan; Liu, Jun; Sun, Hongbin; Wen, Xiaoan
• Is Part Of: ChemMedChem. Volume 12:Number 15(2017)
• Page Start: 1156
• Page End: 1156
• Publication Date: 2017-08-08
• Subjects: ammonium salts -- antagonists -- nitrogen heterocycles -- stability -- structure–activity relationships; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201700431
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract : The front cover picture shows a novel potent muscarinic M3 receptor antagonist ( R )‐3‐[2‐hydroxy‐2, 2‐di(thiophen‐2‐yl)acetoxy]‐1, 1‐dimethylpyrrolidinium bromide (1a : K i =0.16 nm, IC50 =0.38 nm) inhaled to dilate bronchus of patients with chronic obstructive pulmonary disease (COPD).1a and its enantiomer1b have proper stability in human plasma ( t 1/2 =9.34, 19.2 min), while the marketed M3 antagonists aclidinium bromide ( t 1/2 =2.52 min) and glycopyrronium bromide ( t 1/2 >60 min) are either too unstable or overstable in plasma. The newly discovered M3 antagonists1a and1b may have great potential to overcome the clinical drawbacks caused by the extreme instability of aclidinium bromide and the overstablility of glycopyrronium bromide in plasma. More information can be found in the Full Paper by Hongbin Sun, Xiaoan Wen et al. onpage 1173 in Issue 15, 2017 (DOI:10.1002/cmdc.201700189 ).