Novel tricyclic pyrazolopyrimidines as potent and selective GPR119 agonists

作者：Azimioara Mihai^*; Alper Phil; Cow Christopher; Mutnick Daniel; Nikulin Victor; Lelais Gerald; Mecom John; McNeill Matthew; Michellys Pierre Yves; Wang Zhiliang; Reding Esther; Paliotti Michael; Li Jing; Bao Dingjiu; Zoll Jocelyn; Kim Young; Zimmerman Matthew; Groessl Todd; Tuntland Tove; Joseph Sean B; McNamara Peter; Seidel H Martin; Epple Robert

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(23): 5478-5483.

DOI：10.1016/j.bmcl.2014.10.010

• GPCR agonists
• GPR119
• Tricyclic pyrazolopyrimidines
• Type 2 diabetes

Systematic SAR optimization of the GPR119 agonist lead 1, derived from an internal HTS campaign, led to compound 29. Compound 29 displays significantly improved in vitro activity and oral exposure, leading to GLP1 elevation in acutely dosed mice and reduced glucose excursion in an OGTT study in rats at doses >= 10 mg/kg.

• 出版日期2014-12-1