Structural Characteristics of Cannabinoid Type Ⅰ Receptor Antagonists

doi:10.7503/cjcu20120792

Chem. J. Chinese Universities ›› 2013, Vol. 34 ›› Issue (5): 1240.doi: 10.7503/cjcu20120792

• Physical Chemistry • Previous Articles Next Articles

Structural Characteristics of Cannabinoid Type Ⅰ Receptor Antagonists

LIN Ke-Jiang¹, HUANG Zhen-Gui¹, LI Ting², WANG Nan-Xi², CHENG Yao², SHEN Ling-Ling², WANG Yu-Tong², LI Hui², YE Bo-Ping³

1. School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China;
2. Class of National Base of Pharmaceutical Education, China Pharmaceutical University, Nanjing 210009, China;
3. School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China

Received:2012-08-29 Online:2013-05-10 Published:2013-05-10

Abstract

Abstract:

Cannabinoid type Ⅰ receptor(CB1) antagonists offer a new approach to treat obesity and problems related to obesity such as diabetes and cardiometabolic risks. Pharmacophore models were developed via Discovery Studio V2.5 with a training set of 92 CB1 agonists and a test set of 39 compounds. The best hypothesis consisting of five features, namely, a hydrogen bond acceptors, a hydrophobic and two ring aromatic features, has a correlation coefficient of 0.921, a cost difference of 119.132, the root mean square(RMS) of 0.730, and a configuration cost of 16.1229, suggesting that a highly predictive pharmacophore model was successfully obtained. The application of the model shows great success in predicting the activities of the near 450 known CB1 agonists in 12 structural types and provides a guide to design new CB1 antagonists.

Key words: Cannabinoid type Ⅰ receptor antagonist, Pharmacophore, Quantitative structure activity relationship

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LIN Ke-Jiang, HUANG Zhen-Gui, LI Ting, WANG Nan-Xi, CHENG Yao, SHEN Ling-Ling, WANG Yu-Tong, LI Hui, YE Bo-Ping. Structural Characteristics of Cannabinoid Type Ⅰ Receptor Antagonists[J]. Chem. J. Chinese Universities, 2013, 34(5): 1240.

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Structural Characteristics of Cannabinoid Type Ⅰ Receptor Antagonists

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