Synthesis and structure-activity relationship of novel RXR antagonists: orally active anti-diabetic and anti-obesity agents

Junichi Sakaki; Masashi Kishida; Kazuhide Konishi; Hiroki Gunji; Atsushi Toyao; Yuki Matsumoto; Takanori Kanazawa; Hidefumi Uchiyama; Hiroaki Fukaya; Hironobu Mitani; Yoshie Arai; Masaaki Kimura

doi:10.1016/j.bmcl.2007.06.080

Synthesis and structure-activity relationship of novel RXR antagonists: orally active anti-diabetic and anti-obesity agents

Bioorg Med Chem Lett. 2007 Sep 1;17(17):4804-7. doi: 10.1016/j.bmcl.2007.06.080. Epub 2007 Jun 30.

Authors

Junichi Sakaki¹, Masashi Kishida, Kazuhide Konishi, Hiroki Gunji, Atsushi Toyao, Yuki Matsumoto, Takanori Kanazawa, Hidefumi Uchiyama, Hiroaki Fukaya, Hironobu Mitani, Yoshie Arai, Masaaki Kimura

Affiliation

¹ Novartis Institute for Biomedical Research, Tsukuba Research Institute, Ohkubo 8, Tsukuba-Shi, Ibaraki, Japan.

PMID: 17651968
DOI: 10.1016/j.bmcl.2007.06.080

Abstract

A series of diazepinylbenzoic acid derivatives were synthesized and tested in the inhibition assay of the transactivation of RXR. Oral treatment of cyano derivatives (16f) was found to show anti-diabetic and anti-obesity effects in KK-A(y) mice.

MeSH terms

Animals
Anti-Obesity Agents / chemical synthesis*
Anti-Obesity Agents / pharmacology
Body Weight
Dietary Fats
Drug Design
Hypoglycemic Agents / chemical synthesis*
Hypoglycemic Agents / pharmacology
Inhibitory Concentration 50
Male
Mice
Mice, Transgenic
Models, Chemical
Retinoid X Receptor alpha / antagonists & inhibitors*
Retinoid X Receptor alpha / chemical synthesis*
Retinoid X Receptor alpha / chemistry*
Structure-Activity Relationship
Transcriptional Activation

Substances

Anti-Obesity Agents
Dietary Fats
Hypoglycemic Agents
Retinoid X Receptor alpha