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G protein-coupled receptor 119 (GPR119) is expressed in pancreatic islets and intestine, and is involved in insulin and incretin hormone release. GPR119-knockout (Gpr119(-/-)) mice were reported to have normal islet morphology and normal size, body weight (BW), and fed/fasted glucose levels. However, the physiological function of GPR119 and its role in(More)
Inhibition of 11beta-HSD1 has demonstrated potential in the treatment of various components of metabolic syndrome. We wish to report herein the discovery of novel azabicyclic sulfonamide based 11beta-HSD1 inhibitors. Highly potent compounds exhibiting inhibitory activities at both human and mouse 11beta-HSD1 were identified. Several compounds demonstrated(More)
The design and synthesis of two conformationally restricted oxazabicyclo octane derivatives as GRP119 agonists is described. Derivatives of scaffold C, with syn configuration, have the best overall profiles with respect to solubility and in vivo efficacy. Compound 25a was found to have extremely potent agonistic activity and was orally active in lowering(More)
The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure-activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering(More)
[PDF] [Full Text] [Abstract] 2008; 295 (6): R1794-R1802. Am J Physiol Regul Integr Comp Physiol Xiaowen Liu, Sangita G. Murali, Jens J. Holst and Denise M. Ney increased insulin-like growth factor-I responses in rats Enteral nutrients potentiate the intestinotrophic action of glucagon-like peptide-2 in association with [PDF] [Full Text] [Abstract] , May(More)
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