Novel thyroid hormone receptor antagonists with an N-alkylated diphenylamine skeleton.
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.
Komatsu
Takuma
T
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.
Hirano
Tomoya
T
Songkram
Chalermkiat
C
Kawachi
Emiko
E
Kagechika
Hiroyuki
H
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000737:chemistry; D037021:Thyroid Hormone Receptors alpha / Q000037:antagonists & inhibitors*; D037042:Thyroid Hormone Receptors beta / Q000037:antagonists & inhibitors*
D045162:Thiazolidinediones; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D004159:Diphenylamine; C089946:2,4-thiazolidinedione