Synthesis and cannabinoid-1 receptor binding affinity of conformationally constrained analogs of taranabant

被引：7

作者：

Kopka, Ihor E. ^{[1
]}

Lin, Linus S. ^{[1
]}

Jewell, James P. ^{[1
]}

Lanza, Thomas J. ^{[1
]}

Fong, Tung M. ^{[2
]}

Shen, Chun-Pyn ^{[2
]}

Lao, Zhege J. ^{[2
]}

Ha, Sookhee ^{[3
]}

Castonguay, Laurie G. ^{[3
]}

Van der Ploeg, Lex ^{[2
]}

Goulet, Mark T. ^{[1
]}

Hagmann, William K. ^{[1
]}

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Metab Disorders, Rahway, NJ 07065 USA

[3] Merck Res Labs, Dept Mol Modeling, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 16期

关键词：

Cannabinoid; CB1R; Obesity; Conformationally constrained; INVERSE AGONIST; CB1; RECEPTOR; ANTAGONISTS; MK-0364; OBESITY; PERSPECTIVES; DISCOVERY;

D O I：

10.1016/j.bmcl.2010.06.127

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The design, synthesis, and binding activity of ring constrained analogs of the acyclic cannabinoid-1 receptor (CB1R) inverse agonist taranabant 1 are described. The initial inspiration for these taranabant derivatives was its conformation 1a, determined by (1)H NMR, X-ray, and molecular modeling. The constrained analogs were all much less potent than their acyclic parent structure. The results obtained are discussed in the context of a predicted binding of 1 to a homology model of CB1R. (C) 2010 Elsevier Ltd. All rights reserved.

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收藏

页码：4757 / 4761

页数：5

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