Design and synthesis of a novel series of [1-(4-hydroxy-benzyl)-1H-indol-5-yloxy]-acetic acid compounds as potent, selective, thyroid hormone receptor β agonists

被引：7

作者：

Burkholder, Timothy P. ^{[1
]}

Cunningham, Brian E. ^{[1
]}

Clayton, Joshua R. ^{[1
]}

Lander, Peter A. ^{[1
]}

Brown, Matthew L. ^{[1
]}

Doti, Robert A. ^{[1
]}

Durst, Gregory L. ^{[1
]}

Montrose-Rafizadeh, Chahrzad ^{[2
]}

King, Constance ^{[2
]}

Osborne, Harold E. ^{[2
]}

Amos, Robert M. ^{[2
]}

Zink, Richard W. ^{[2
]}

Stramm, Lawrence E. ^{[2
]}

Burris, Thomas P. ^{[3
]}

Cardona, Guemalli ^{[3
]}

Konkol, Debra L. ^{[4
]}

Reidy, Charles ^{[4
]}

Christe, Michael E. ^{[4
]}

Genin, Michael J. ^{[1
]}

机构：

[1] Lilly Corp Ctr, Div Eli Lilly & Co, Lilly Res Labs, Discovery Chem Res & Technol, Indianapolis, IN 46285 USA

[2] Lilly Corp Ctr, Div Eli Lilly & Co, Lilly Res Labs, Lead Optimizat Biol, Indianapolis, IN 46285 USA

[3] Lilly Corp Ctr, Div Eli Lilly & Co, Lilly Res Labs, Bone & Inflammat Therapeut Area, Indianapolis, IN 46285 USA

[4] Lilly Corp Ctr, Div Eli Lilly & Co, Lilly Res Labs, Diabet Therapeut Area, Indianapolis, IN 46285 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 07期

关键词：

Thyroid hormone; Agonist; TR-beta; Indole; THYROMIMETICS; LIGANDS; DISEASE; SYSTEM;

D O I：

10.1016/j.bmcl.2015.02.062

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The design, synthesis, and structure activity relationships for a novel series of indoles as potent, selective, thyroid hormone receptor beta (TR beta) agonists is described. Compounds with >50 x binding selectivity for TRb over TR alpha were generated and evaluation of compound 1c from this series in a model of dyslipidemia demonstrated positive effects on plasma lipid endpoints in vivo. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：1377 / 1380

页数：4

共 22 条

[1]

Blange I, 1997, BIOL PHARM BULL, V20, P1123

[2] Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor [J].