Development of two synthetic routes to CE-178,253, a CB1 antagonist for the treatment of obesity

被引：24

作者：

Brandt, Thomas A. ^{[2
]}

Caron, Stephane ^{[1
]}

Damon, David B. ^{[3
]}

DiBrino, Joseph ^{[5
]}

Ghosh, Arun ^{[1
]}

Griffith, David A. ^{[5
]}

Kedia, Sandeep ^{[4
]}

Ragan, John A. ^{[1
]}

Rose, Peter R. ^{[3
]}

Vanderplas, Brian C. ^{[1
]}

Wei, Lulin ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Chem Res & Dev, Groton, CT 06335 USA

[2] Pfizer Global Res & Dev, Res API, Groton, CT 06335 USA

[3] Pfizer Global Res & Dev, Mat Sci, Groton, CT 06335 USA

[4] Pfizer Global Res & Dev, Supply Chain, Groton, CT 06335 USA

[5] Pfizer Global Res & Dev, Dept Cardiovasc Metab & Endocrine Dis, Groton, CT 06335 USA

来源：

TETRAHEDRON | 2009年 / 65卷 / 16期

关键词：

CB1; antagonist; Obesity; 1,3,5]-Triazine; Pyrazolotriazine; Suzuki coupling; Thiosemicarbazide; RECEPTOR INVERSE AGONIST; ENDOCANNABINOID SYSTEM; ENERGY-BALANCE; CANNABINOID CB; BODY-WEIGHT; FOOD-INTAKE; RIMONABANT; RATS;

D O I：

10.1016/j.tet.2008.10.067

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

CE-178,253 benzenesulfonate (1) is a CB1 antagonist discovered by Pfizer medicinal chemists. Two syntheses Of this compound are described. The first, based on the discovery synthesis, involves assembly of an aryl-substituted pyrazolotriazine core onto which the second aryl moiety is installed by a Suzuki Coupling: this route has been scaled to provide up to 6 kg of API. A second. more convergent route is also described, which installs the pyrazolotriazine containing both aryl substituents by condensation of a bromoketone with a substituted thiosemicarbazide. This route has been demonstrated on laboratory scale and is viewed as the preferred bond-forming sequence. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：3292 / 3304

页数：13

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