Towards rational design of cannabinoid receptor 1 (CB1) antagonists for peripheral selectivity

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Fulp, Alan¹  Bortoff, Katherine¹  Zhang, Yanan³  Seltzman, Herbert²  Snyder, Rodney¹  Maitra, Rangan¹ 

[1] RTI Int, Pharmacol & Toxicol, Res Triangle Pk, NC 27709 USA

[2] RTI Int, Organ & Med Chem, Res Triangle Pk, NC 27709 USA

[3] RTI Int, Analyt Chem & Pharmaceut, Res Triangle Pk, NC 27709 USA

关键词: CB1;    Peripheral;    Antagonist;    Cannabinoid;    Topological polar surface area;   

DOI  :  10.1016/j.bmcl.2011.08.032

来源: Elsevier

【 摘 要 】

CB1 receptor antagonists that are peripherally restricted were targeted. Compounds with permanent charge as well as compounds that have increased polar surface area were made and tested against CB1 for binding and activity. Sulfonamide and sulfamide with high polar surface area and good activity at CB1 were rationally designed and pharmacologically tested. Further optimization of these compounds and testing could lead to the development of a new class of therapeutics to treat disorders where the CB1 receptor system has been implicated. (C) 2011 Elsevier Ltd. All rights reserved.

【 授权许可】

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