1092062-74-2Relevant articles and documents
CD73 INHIBITORS
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Paragraph 0212, (2020/03/23)
Compounds that modulate the conversion of AMP to adenosine by 5'-nucleotidase, ecto, and compositions containing the compounds and methods for synthesizing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by 5'-nucleotidase, ecto is also provided.
Indazole-6-phenylcyclopropylcarboxylic Acids as Selective GPR120 Agonists with in Vivo Efficacy
McCoull, William,Bailey, Andrew,Barton, Peter,Birch, Alan M.,Brown, Alastair J. H.,Butler, Hayley S.,Boyd, Scott,Butlin, Roger J.,Chappell, Ben,Clarkson, Paul,Collins, Shelley,Davies, Robert M. D.,Ertan, Anne,Hammond, Clare D.,Holmes, Jane L.,Lenaghan, Carol,Midha, Anita,Morentin-Gutierrez, Pablo,Moore, Jane E.,Raubo, Piotr,Robb, Graeme
, p. 3187 - 3197 (2017/04/19)
GPR120 agonists have therapeutic potential for the treatment of diabetes, but few selective agonists have been reported. We identified an indazole-6-phenylcyclopropylcarboxylic acid series of GPR120 agonists and conducted SAR studies to optimize GPR120 potency. Furthermore, we identified a (S,S)-cyclopropylcarboxylic acid structural motif which gave selectivity against GPR40. Good oral exposure was obtained with some compounds displaying unexpected high CNS penetration. Increased MDCK efflux was utilized to identify compounds such as 33 with lower CNS penetration, and activity in oral glucose tolerance studies was demonstrated. Differential activity was observed in GPR120 null and wild-type mice indicating that this effect operates through a mechanism involving GPR120 agonism.
