(-)-Cercosporamide derivatives as novel antihyperglycemic agents.
In our exploratory campaign for an antihyperglycemic agent with a novel mechanism of action, (-)-Cercosporamide 1, which is known as an antifungal agent, showed a potent plasma glucose lowering effect in hyperglycemic KK/Ta mice. The trouble was that it was accompanied by a decrease in food intake and a loss of body weight. We synthesized some (-)-Cercosporamide derivatives and succeeded to separate these actions. N,O-ketal type derivatives, especially compound 10, had the most potent plasma glucose lowering effect without affecting the food consumption or body weight.
Furukawa
Akihiro
A
Shinagawa R&D Center, Daiichi Sankyo Co., Ltd, 1-2-58, Shinagawa-ku, Tokyo, Japan. furukawa.akihiro.zy@daiichisankyo.co.jp
Arita
Tsuyoshi
T
Satoh
Susumu
S
Araki
Kazushi
K
Kuroha
Masanori
M
Ohsumi
Jun
J
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents; D020128:Inhibitory Concentration 50; D051379:Mice; D008822:Mice, Transgenic; D008956:Models, Chemical
D000935:Antifungal Agents; D001572:Benzofurans; D001786:Blood Glucose; D007004:Hypoglycemic Agents; C085452:cercosporamide