Synthesis and structure-activity relationship of novel RXR antagonists: orally active anti-diabetic and anti-obesity agents.
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.
Sakaki
Junichi
J
Novartis Institute for Biomedical Research, Tsukuba Research Institute, Ohkubo 8, Tsukuba-Shi, Ibaraki, Japan.
Kishida
Masashi
M
Konishi
Kazuhide
K
Gunji
Hiroki
H
Toyao
Atsushi
A
Matsumoto
Yuki
Y
Kanazawa
Takanori
T
Uchiyama
Hidefumi
H
Fukaya
Hiroaki
H
Mitani
Hironobu
H
Arai
Yoshie
Y
Kimura
Masaaki
M
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001835:Body Weight; D004041:Dietary Fats; D015195:Drug Design; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008956:Models, Chemical; D047490:Retinoid X Receptor alpha / Q000037:antagonists & inhibitors* / Q000138:chemical synthesis* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
D019440:Anti-Obesity Agents; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D047490:Retinoid X Receptor alpha