885038-84-6Relevant articles and documents
Synthesis and structure-activity relationship of fused-pyrimidine derivatives as a series of novel GPR119 agonists
Negoro, Kenji,Yonetoku, Yasuhiro,Moritomo, Ayako,Hayakawa, Masahiko,Iikubo, Kazuhiko,Yoshida, Shigeru,Takeuchi, Makoto,Ohta, Mitsuaki
, p. 6442 - 6451,10 (2012/12/12)
A series of fused-pyrimidine derivatives have been discovered as potent and orally active GPR119 agonists. A combination of the fused-pyrimidine structure and 4-chloro-2,5-difluorophenyl group provided the 5,7-dihydrothieno[3,4-d] pyrimidine 6,6-dioxide derivative 14a as a highly potent GPR119 agonist. Further optimization of the amino group at the 4-position in the pyrimidine ring led to the identification of 2-{1-[2-(4-chloro-2,5-difluorophenyl)-6,6-dioxido-5,7- dihydrothieno[3,4-d]pyrimidin-4-yl]piperidin-4-yl}acetamide (16b) as an advanced analog. Compound 16b was found to have extremely potent agonistic activity and improved glucose tolerance at 0.1 mg/kg po in mice. We consider compound 16b and its analogs to have clear utility in exploring the practicality of GPR119 agonists as potential therapeutic agents for the treatment of type 2 diabetes mellitus.
