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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Design and synthesis of novel and potent GPR119 agonists with a spirocyclic structure
Kazuhito Harada1, Jun Mizukami1, Sho Kadowaki1
1Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1, Murasaki-cho, Takatsuki, Osaka 569-1125, Japan.
Abstract:
Exploration of alternative structures of the substituted piperidine or piperazine ring which are characteristic in most of the reported GPR119 agonists provided novel spirocyclic cyclohexane derivatives. The representative 17 with a high three-dimensionality exhibited potent agonistic activity (EC50 = 4 nM) with no CYP inhibitory activity (IC50 >10 μM). Compound 17 also displayed hypoglycemic activity with insulin secretion dependent on glucose concentration in an intraperitoneal glucose tolerance test in rats.
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