323182-79-2

Upstream product

• 900-91-4 3,3,3-triphenylpropionic acid 
• 43041-12-9 methyl (2R)-pyrrolidine-2-carboxylate 
• 6404-31-5 Z-D-proline 
• 85201-91-8 (2S,4R)-4-tert-butoxy-pyrrolidine-1,2-dicarboxylic acid 1-benzyl ester 
• 182210-00-0 methyl (2R)-(benzyloxycarbonyl)pyrrolidine-2-carboxylate 
• 144222-22-0 tert-butyl 4-(aminomethyl)piperidine-1-carboxylate 
• 911296-66-7 methyl (2R)-1-([(2S,4R)-4-tert-butoxy-1-pyrrolidin-2-yl]carbonyl)pyrrolidine-2-carboxylate 
• 545380-39-0 methyl (2R)-1-([(2S,4R)-4-tert-butoxy-1-(benzyloxycarbonyl)pyrrolidin-2-yl]carbonyl)pyrrolidine-2-carboxylate 
• 323183-79-5 (2R)-1-{(2S,4R)-4-(tert-butoxy)-1-(3,3,3-triphenylpropanoyl)pyrrolidin-2-yl}carbonylpyrrolidine-2-carboxylic acid 
• 545380-40-3 (R)-1-[(2S,4R)-4-tert-Butoxy-1-(3,3,3-triphenyl-propionyl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Identification of a novel 4-aminomethylpiperidine class of M3 muscarinic receptor antagonists and structural insight into their M3 selectivity

Identification of a novel class of potent and highly selective M 3 muscarinic antagonists is described. First, the structure-activity relationship in the cationic amine core of our previously reported triphenylpropionamide class of M3 selective antagonists was explored by a small diamine library constructed in solid phase. This led to the identification of M3 antagonists with a novel piperidine pharmacophore and significantly improved subtype selectivity from a previously reported class. Successive modification on the terminal triphenylpropionamide part of the newly identified class gave 14a as a potent M3 selective antagonist that had > 100-fold selectivity versus the M1, M 2, M4, and M5 receptors (M3: K i = 0.30 nM, M1/M3 = 570-fold, M 2/M3 = 1600-fold, M4/M3 = 140-fold, M5/M3 = 12000-fold). The possible rationale for its extraordinarily higher subtype selectivity than reported M3 antagonists was hypothesized by sequence alignment of multiple muscarinic receptors and a computational docking of 14a into transmembrane domains of M3 receptors.

NOVEL AMIDE DERIVATIVES

This invention relates to compounds which are represented by the general formula [I] ???[in which A stands for a group of the following formula [ao] or [b0] ???Ar1, Ar2 and Ar3 stand for optionally substituted phenyl; k stands for 0 or 1; m, n and s stand for 0, 1 or 2; R1 stands for hydrogen or optionally substituted lower alkyl; R2, R3, R4 and R5 either stand for hydrogen or optionally substituted lower alkyl, or R2 and R3, or R4 and R5 together stand for trimethylene and the like; R60 stands for hydrogen, alkyl, or the like; R61and R71 either stand for alkyl and the like, or together stand for trimethylene and the like; X stands for carbonyl or methylene; Y stands for nitrogen or methine; and Q- stands for anion], and the like. The compounds of the invention exhibit selective antagonism to muscarinic M3 receptors, and therefore are useful as safe and effective agents showing little side effect, for treating diseases of the respiratory, urinary and digestive systems.