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Paper | Special issue | Vol 90, No. 1, 2015, pp.372-404
Published online, 12th June, 2014
DOI: 10.3987/COM-14-S(K)29
Synthesis and Evaluations of GLP-1 Secretion and Anti-Diabetic Effect in KKAy Mice of New Tricyclic Compounds

Daisuke Minehira, Daisuke Takeda, Shota Miyawaki, Atsushi Kato, Isao Adachi,* Akira Miyazaki, Ryuta Miyatake, Masahito Umezaki, Kyoko Miura, Yoshiro Kitahara, Kenji Sugimoto, Yuji Matsuya, and Naoki Toyooka*

*Graduate School of Science and Technology, Toyama University, Gofuku 3190, Toyama 930-8555, Japan


Glucagon-like peptide-1 (GLP-1), which belongs to the family of incretins, plays important role for the regulation of plasma glucose. Accordingly, GLP-1-based therapies for type 2 diabetes have recognized as one of the most interesting target. In this study, we have found the new tricyclic compounds having strong GLP-1 secretion from human intestinal L cells, and anti-diabetic properties in spontaneously obese and diabetic KKAy mice. The most potent compound 5ka was obtained as the unexpected product, and we would like to report the details of the synthesis, structure elucidations, pharmacological activities on secretion of GLP-1, and anti-diabetic effects using diabetic KKAy mice.