1243285-53-1Relevant articles and documents
Method for preparing aryl cyclopropyl ether and derivative thereof
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Paragraph 0030; 0040-0043; 0066-0068; 0069-0071, (2019/02/10)
The invention discloses a method for preparing aryl cyclopropyl ether and a derivative thereof. The method includes: under the protection of an inert gas, dissolving a fluoro aromatic compound and cyclopropanol in a nonprotic dipolar solvent, adding a bas
Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5)
Chen, Tao,Reich, Nicholas William,Bell, Noah,Finn, Patricia D.,Rodriguez, David,Kohler, Jill,Kozuka, Kenji,He, Limin,Spencer, Andrew G.,Charmot, Dominique,Navre, Marc,Carreras, Christopher W.,Koo-Mccoy, Samantha,Tabora, Jocelyn,Caldwell, Jeremy S.,Jacobs, Jeffrey W.,Lewis, Jason Gustaf
supporting information, p. 7589 - 7613 (2018/09/12)
Bile acid signaling and metabolism in the gastrointestinal tract have wide-ranging influences on systemic disease. G protein-coupled bile acid receptor 1 (GPBAR1, TGR5) is one of the major effectors in bile acid sensing, with demonstrated influence on metabolic, inflammatory, and proliferative processes. The pharmacologic utility of TGR5 agonists has been limited by systemic target-related effects such as excessive gallbladder filling and blockade of gallbladder emptying. Gut-restricted TGR5 agonists, however, have the potential to avoid these side effects and consequently be developed into drugs with acceptable safety profiles. We describe the discovery and optimization of a series of gut-restricted TGR5 agonists that elicit a potent response in mice, with minimal gallbladder-related effects. The series includes 12 (TGR5 EC50: human, 143 nM; mouse, 1.2 nM), a compound with minimal systemic availability that may have therapeutic value to patients with type 2 diabetes mellitus, nonalcoholic steatohepatitis, or inflammatory bowel disease.
