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.
Naoki Takahashi  1 ,  Koji Maeda  1 ,  Yukiyasu Asano  2 ,  Nobuhide Watanabe  3
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: [email protected].
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.