- A Novel Strategy for the Construction of Covalent Organic Frameworks from Nonporous Covalent Organic Polymers
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The field of covalent organic frameworks (COFs) has been developed significantly in the past decade on account of their important characteristics and vast application potential. On the other hand, the discovery of novel synthetic methodology is still a ch
- Miao, Zhuang,Liu, Guiyan,Cui, Yumeng,Liu, Zhengyu,Li, Jinheng,Han, Fangwai,Liu, Yu,Sun, Xiaoxiao,Gong, Xuefang,Zhai, Yufeng,Zhao, Yanli,Zeng, Yongfei
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supporting information
p. 4906 - 4910
(2019/03/11)
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- Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5)
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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.
- 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
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supporting information
p. 7589 - 7613
(2018/09/12)
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- NON-SYSTEMIC TGR5 AGONISTS
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Compounds of structure (I), or a stereoisomer, tautomer, pharmaceutically acceptable salt or prodrug thereof, wherein R1, R2, R3, R4, R8, R9, R10, R11, R12, A1, A2, X, Y and Z are as defined herein. Uses of such compounds as TGR5 antagonists and for treatment of various indications, including Type II diabetes meletus are also provided.
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Page/Page column 213; 214
(2013/07/05)
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