Selective 5-HT2C receptor agonists: Design and synthesis of pyridazine-fused azepines

被引：5
作者：
Green, Martin P. [1 ]
McMurray, Gordon [2 ]
Storer, R. Ian [1 ]
机构：
[1] Sandwich Labs, Pfizer Global Res & Dev, Worldwide Med Chem, Sandwich CT13 9NJ, Kent, England
[2] Sandwich Labs, Pfizer Global Res & Dev, Discovery Biol, Sandwich CT13 9NJ, Kent, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 16期
关键词：
5-HT2C receptor agonists; CNS penetration; Obesity; Pyridazino[3,4-d]azepines; Urinary incontinence; P-GLYCOPROTEIN; IN-VITRO; LORCASERIN; DISCOVERY; POTENT; DRUGS; PERMEABILITY; LIGANDS; OBESITY; CNS;
D O I：
10.1016/j.bmcl.2016.06.060
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Heterocycle-fused azepines are discussed as potent 5-HT2C receptor agonists with excellent selectivity over 5-HT2B agonism. Synthesis and structure activity relationships are outlined for a series of bicyclic pyridazino[3,4-d]azepines. By comparison with earlier published work, in vitro assays predict a high probability for achieving CNS penetration for a potent and selective compound 15a, a pre-requisite to achieve in vivo efficacy. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4117 / 4121
页数：5
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