88912-22-5Relevant academic research and scientific papers
Pharmacological Evaluation of Novel Bioisosteres of an Adamantanyl Benzamide P2X7 Receptor Antagonist
Wilkinson, Shane M.,Barron, Melissa L.,O'Brien-Brown, James,Janssen, Bieneke,Stokes, Leanne,Werry, Eryn L.,Chishty, Mansoor,Skarratt, Kristen K.,Ong, Jennifer A.,Hibbs, David E.,Vugts, Danielle J.,Fuller, Stephen,Windhorst, Albert D.,Kassiou, Michael
, p. 2374 - 2380 (2017/11/21)
Adamantanyl benzamide 1 was identified as a potent P2X7R antagonist but failed to progress further due to poor metabolic stability. We describe the synthesis and SAR of a series of bioisosteres of benzamide 1 to explore improvements in the pharmacological properties of this lead. Initial efforts investigated a series of heteroaromatic bioisosteres, which demonstrated improved physicochemical properties but reduced P2X7R antagonism. Installation of bioisosteric fluorine on the adamantane bridgeheads was well tolerated and led to a series of bioisosteres with improved physicochemical properties and metabolic stability. Trifluorinated benzamide 34 demonstrated optimal physicochemical parameters, superior metabolic stability (ten times longer than lead benzamide 1), and an improved physicokinetic profile and proved effective in the presence of several known P2X7R polymorphisms.
GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES
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Page/Page column 149; 150, (2017/03/17)
Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula II.
GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES
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Page/Page column 164; 165, (2017/03/08)
Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (I), as follows: wherein R1, R2, R4, W, X, Y, and G, are defined herein.
GPR40 AGONISTS FOR THE TREATMENT OF TYPE II DIABETES
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Page/Page column 160; 161, (2017/03/08)
Disclosed are compounds, compositions and methods for treating of disorders that are affected by the modulation of the GPR40 receptor. Such compounds are represented by Formula (III); wherein R1c, R2C, R4C, Wc, Yc, Zc and Gc, are defined herein.
