Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-γ binding agents with potential application to the treatment of osteoporosis

被引：45

作者：

Hopkins, Corey R. ^{[1
]}

O'Neil, Steven V. ^{[1
]}

Laufersweiler, Michael C. ^{[1
]}

Wang, Yili ^{[1
]}

Pokross, Matthew ^{[1
]}

Mekel, Marlene ^{[1
]}

Evdokimov, Artem ^{[1
]}

Walter, Richard ^{[1
]}

Kontoyianni, Maria ^{[1
]}

Petrey, Maria E. ^{[1
]}

Sabatakos, Georgios ^{[1
]}

Roesgen, Jeff T. ^{[1
]}

Richardson, Eloise ^{[1
]}

Demuth, Thomas P., Jr. ^{[1
]}

机构：

[1] Procter & Gamble Pharmaceut Hlth Care Res Ctr, Mason, OH 45040 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 21期

关键词：

PPAR; N-sulfonyl-2-indole carboxamides; alkaline phosphatase assay; osteoporosis; ACTIVATED RECEPTOR-GAMMA; BLOCKS ADIPOCYTE DIFFERENTIATION; OSTEOBLAST DIFFERENTIATION; LIGAND-BINDING; BONE LOSS; AGONISTS; ROSIGLITAZONE; ADIPOGENESIS; ANTAGONIST; MODULATORS;

D O I：

10.1016/j.bmcl.2006.08.003

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and structure-activity relationships of a novel series of N-sulfonyl-2-indole carboxamides that bind to peroxisome proliferator-activated receptor gamma (PPAR-gamma) are reported. Chemical optimization of the series led to the identification of 4q (IC50 = 50 nM) as a potent binding agent of PPAR-gamma. Also reported is preliminary cell based data suggesting the use of these compounds in the treatment of osteoporosis. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：5659 / 5663

页数：5

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