Synthesis and pharmacological characterization of 1-benzyl-4-aminoindole-based thyroid hormone receptor β agonists

Naoki Takahashi; Koji Maeda; Yukiyasu Asano; Nobuhide Watanabe

doi:10.1016/j.bmc.2013.11.001

Synthesis and pharmacological characterization of 1-benzyl-4-aminoindole-based thyroid hormone receptor β agonists

Bioorg Med Chem. 2014 Jan 1;22(1):488-98. doi: 10.1016/j.bmc.2013.11.001. Epub 2013 Nov 13.

Authors

Naoki Takahashi¹, Koji Maeda¹, Yukiyasu Asano², Nobuhide Watanabe³

Affiliations

¹ Drug Discovery Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd, 363 Shiosaki, Hokusei-cho, Inabe-city, Mie 511-0406, Japan.
² Product Planning II, R&D Planning Department, R&D Strategy Center, Sanwa Kagaku Kenkyusho Co., Ltd, 35 Higashisotobori-cho, Higashi-ku, Nagoya 461-8631, Japan.
³ Drug Discovery Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd, 363 Shiosaki, Hokusei-cho, Inabe-city, Mie 511-0406, Japan. Electronic address: no_watanabe@skk-net.com.

PMID: 24290064
DOI: 10.1016/j.bmc.2013.11.001

Abstract

A series of 1-benzylindole-based TRβ agonists were prepared and evaluated. Compounds 11b' and 11c' were found to have cholesterol-lowering in a rat model with marginal effects on cardiac function and HPT axis. The present work illustrates the potential use of indoles as inner ring isosteres.

Keywords: Dyslipidemia; Hypothalamic/pituitary/thyroid axis; Thyroid hormone receptor β agonists; Thyroid stimulating hormone.

MeSH terms

Animals
Indoles / chemical synthesis*
Indoles / pharmacology
Rats
Thyroid Hormone Receptors beta / agonists
Thyroid Hormone Receptors beta / drug effects*

Substances

Indoles
Thyroid Hormone Receptors beta
1-benzylindole