Synthesis and biological evaluation of novel hexahydro-pyrido[3′,2′:4,5]pyrrolo[1,2-a]pyrazines as potent and selective 5-HT2C receptor agonists

被引：29
|
作者：
Richter, HGF [1 ]
Adams, DR
Benardeau, A
Bickerdike, MJ
Bentley, JM
Blench, TJ
Cliffe, IA
Dourish, C
Hebeisen, P
Kennett, GA
Knight, AR
Malcolm, CS
Mattei, P
Misra, A
Mizrahi, J
Monck, NJT
Plancher, JM
Roever, S
Roffey, JRA
Taylor, S
Vickers, SP
机构：
[1] F Hoffmann La Roche Ltd, Discovery Res, CH-4070 Basel, Switzerland
[2] Vernalis Res Ltd, Wokingham RG41 5UA, Berks, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 05期
关键词：
5-HT2C receptor agonist; pyrido[3 ',2 ': 4,5]pyrrolo[1,2-a]pyrazines; obesity; phospholipidosis; hERG;
D O I：
10.1016/j.bmcl.2005.11.083
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Further lead optimization efforts on previously described 1,2,3,4,10,10a-hexahydro-1H-pyrazino[1,2-a]indoles led to the new class of 5,Sa,6,7.8;9-hexahydro-pyrido[3',2':4,5]pyrrolo[1,2-a]pyrazines culminating in the discovery of (5aR,9R)-2-[(cyclopropylmethoxy)methyl]-5;5a.6;7,8,9-hexahydro-9-methyl-pyrido[3', 2':4,5]pyrrolo[1,2-a]pyrazine 18 as a potent, full 5-HT2C receptor agonist with an outstanding selectivity profile and excellent hERG and phospholipidosis properties. (C) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1207 / 1211
页数：5
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