New bicyclic cannabinoid receptor-1 (CB1-R) antagonists

被引：38

作者：

Carpino, PA ^{[1
]}

Griffith, DA ^{[1
]}

Sakya, S ^{[1
]}

Dow, RL ^{[1
]}

Black, SC ^{[1
]}

Hadcock, JR ^{[1
]}

Iredale, PA ^{[1
]}

Scott, DO ^{[1
]}

Fichtner, MW ^{[1
]}

Rose, CR ^{[1
]}

Day, R ^{[1
]}

Dibrino, J ^{[1
]}

Butler, M ^{[1
]}

DeBartolo, DB ^{[1
]}

Dutcher, D ^{[1
]}

Gautreau, D ^{[1
]}

Lizano, JS ^{[1
]}

O'Connor, RE ^{[1
]}

Sands, MA ^{[1
]}

Kelly-Sullivan, D ^{[1
]}

Ward, KM ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton Labs, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 03期

关键词：

cannabinoid receptor antagonists; CB1-R; 2,6-dihydropyrazolo[4,3-d]pyrimidin-7-one; 2,6-dihydro-pyrazolo[3,4-c]pyridin-7-one; 2,6-dihydro-pyrazolo[3,4-d]pyridazin-7-one; 1,9-dihydro-purin-6-one; obesity; conformational restriction;

D O I：

10.1016/j.bmcl.2005.10.019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of conformationally constrained bicyclic derivatives derived from SR141716 was prepared and evaluated as hCB(1)-R antagonists and inverse agonists. Optimization of the structure-activity relationships around the 2,6-dihydro-pyrazolo[4,3 -d]pyrimidin-7-one derivative 2a led to the identification of two compounds with oral activity in rodent feeding models (2h and 4a). Replacement of the PP group in 2h with other bicyclic groups resulted in a loss of binding affinity. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：731 / 736

页数：6

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