Design, synthesis and biological evaluation of novel 7-azaspiro[3.5]nonane derivatives as GPR119 agonists

Publication date: Available online 20 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Daisuke Matsuda, Madoka Kawamura, Yohei Kobashi, Fumiyasu Shiozawa, Youichirou Suga, Keiko Fusegi, Shinichi Nishimoto, Kayo Kimura, Masako Miyoshi, Noriko Takayama, Hiroyuki Kakinuma, Norikazu Ohtake
The design and synthesis of a novel class of 7-azaspiro[3.5]nonane GPR119 agonists are described. In this series, optimization of the right piperidine N-capping group (R²) and the left aryl group (R³) led to the identification of compound 54g as a potent GPR119 agonist. Compound 54g showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose lowering effect in diabetic rats.

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