Novel thyroid hormone receptor antagonists with an N-alkylated diphenylamine skeleton

Takuma Komatsu; Tomoya Hirano; Chalermkiat Songkram; Emiko Kawachi; Hiroyuki Kagechika

doi:10.1016/j.bmc.2007.02.053

Novel thyroid hormone receptor antagonists with an N-alkylated diphenylamine skeleton

Bioorg Med Chem. 2007 May 1;15(9):3115-26. doi: 10.1016/j.bmc.2007.02.053. Epub 2007 Mar 3.

Authors

Takuma Komatsu¹, Tomoya Hirano, Chalermkiat Songkram, Emiko Kawachi, Hiroyuki Kagechika

Affiliation

¹ School of Biomedical Science, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.

PMID: 17363258
DOI: 10.1016/j.bmc.2007.02.053

Abstract

Thyroid hormones play important roles in growth, development and homeostasis, and disruption of their functions induces serious disease, so novel synthetic thyroid hormone analogues are candidates for clinical application. We designed and synthesized novel diphenylamine derivatives with a thiazolidinedione moiety as the terminal polar group as thyroid hormone receptor (TR) antagonists. Compounds bearing an appropriately sized N-alkyl group showed antagonistic activities towards both the hTRalpha1 and hTRbeta1 subtypes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
COS Cells
Chlorocebus aethiops
Diphenylamine / analogs & derivatives
Diphenylamine / chemical synthesis
Diphenylamine / pharmacology*
Drug Design
Humans
Molecular Structure
Stereoisomerism
Structure-Activity Relationship
Thiazolidinediones / chemistry
Thyroid Hormone Receptors alpha / antagonists & inhibitors*
Thyroid Hormone Receptors beta / antagonists & inhibitors*

Substances

Thiazolidinediones
Thyroid Hormone Receptors alpha
Thyroid Hormone Receptors beta
Diphenylamine
2,4-thiazolidinedione