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Updated: Jul 17, 2026

Quantifying Agonist Activity at G Protein-coupled Receptors
Published on: December 26, 2011
Quantitative structure-selectivity relationship for M2 selectivity between M1 and M2 of piperidinyl piperidine
Yin-Yao Niu1, Li-Min Yang, Ke-Min Deng
1Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Abstract:
Muscarinic M2 receptor antagonists with high subtype selectivity (M2/M1) will decrease the toxicity in central nervous system in treatment of AD. The exploration of quantitative structure-selectivity relationship (QSSR) to muscarinic M2 receptor antagonists will provide design information for drug with fewer side effects. In this paper, CoMFA models of pK(i)(M1), pK(i)(M2) and p[K(i)(M2)/K(i)(M1)] (pK(i)(M2)-pK(i)(M1)) were used to study the subtype selectivity (M2/M1) of piperidinyl piperidine derivatives as muscarinic M2 subtype receptor antagonists. The parameters of the three models are: 0.633, 0.636 and 0.726 for cross-validated r(2) (r(cv)(2)), 0.109, 0.204 and 0.09 for the Standard error of estimate (SD), respectively. The results show the model of p[K(i)(M2)/K(i)(M1)] is the best one for design of piperidinyl piperidine derivatives as muscarinic antagonists with high subtype selectivity (M2/M1).
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