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

共 50 条

[1] Cannabinoid CB1 Receptor Antagonists
Thomas, Brian F.
DRUG DEVELOPMENT RESEARCH, 2009, 70 (08) : 525 - 526
[2] CB1 cannabinoid receptor antagonists
Barth, F
ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 40, 2005, 40 : 103 - 118
[3] Recent advances in CB1 cannabinoid receptor antagonists
Lange, JHM
Kruse, CG
CURRENT OPINION IN DRUG DISCOVERY & DEVELOPMENT, 2004, 7 (04) : 498 - 506
[4] Cannabinoid CB1 receptor antagonists as promising new medications for drug dependence
Le Foll, B
Goldberg, SR
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 312 (03): : 875 - 883
[5] 1,2,3-Triazole derivatives as new cannabinoid CB1 receptor antagonists
Hou, Duen-Ren
Alam, Safiul
Kuan, Ting-Chun
Ramanathan, Mani
Lin, Tsung-Pang
Hung, Ming-Shiu
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (03) : 1022 - 1025
[6] Cannabinoid CB1 receptor antagonists in therapeutic and structural perspectives
Lange, Jos H. M.
Kruse, Chris G.
CHEMICAL RECORD, 2008, 8 (03): : 156 - 168
[7] Recent CB1 Cannabinoid Receptor Antagonists and Inverse Agonists
Seltzman, Herbert H.
DRUG DEVELOPMENT RESEARCH, 2009, 70 (08) : 601 - 615
[8] CANNABINOID RECEPTOR CB1 ANTAGONISTS: STATE OF THE ART AND CHALLENGES
Bifulco, Maurizio
Santoro, Antonietta
Laezza, Chiara
Malfitano, Anna Maria
VITAMINS AND HORMONES: ANANDAMIDE AN ENDOGENOUS CANNABINOID, 2009, 81 : 159 - 189
[9] Medicinal chemistry strategies to CB1 cannabinoid receptor antagonists
Lange, JHM
Kruse, CG
DRUG DISCOVERY TODAY, 2005, 10 (10) : 693 - 702
[10] Cannabinoid1 (CB-1) receptor antagonists: a molecular approach to treating acute cannabinoid overdose
Skolnick, Phil
Crystal, Roger
JOURNAL OF NEURAL TRANSMISSION, 2020, 127 (02) : 279 - 286

← 1 2 3 4 5 →