Design and synthesis of potent carboxylic acid DGAT1 inhibitors with high cell permeability

被引：11

作者：

Bali, Ustav ^{[1
]}

Barba, Oscar ^{[1
]}

Dawson, Graham ^{[1
]}

Gattrell, William T. ^{[1
]}

Horswill, James G. ^{[1
]}

Pan, David A. ^{[1
]}

Procter, Martin J. ^{[1
]}

Rasamison, Chrystelle M. ^{[1
]}

Smith, Colin P. Sambrook ^{[1
]}

Taylor-Warne, Amanda ^{[1
]}

Wong-Kai-In, Philippe ^{[1
]}

机构：

[1] Prosidion Ltd, Windrush Court, Oxford OX4 6LT, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 02期

关键词：

DGAT1; Obesity; Permeability; Efflux; OBESITY; DISCOVERY; MICE;

D O I：

10.1016/j.bmcl.2011.12.050

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of potent carboxylic acid DGAT1 inhibitors with high permeability were developed from a virtual screening hit. Strategies were employed to reduce Pgp substrate recognition and increase passive permeability, resulting in the discovery of a series showing good inhibition of cellular triglyceride synthesis. The mutagenic potential of prospective metabolites was evaluated in the Ames assay, and one aniline was shown to be devoid of mutagenicity. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：824 / 828

页数：5

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