851224-79-8Relevant academic research and scientific papers
Discovery of an Isothiazole-Based Phenylpropanoic Acid GPR120 Agonist as a Development Candidate for Type 2 Diabetes
Zhang, Xuqing,Cai, Chaozhong,Sui, Zhihua,Macielag, Mark,Wang, Yuanping,Yan, Wen,Suckow, Arthur,Hua, Hong,Bell, Austin,Haug, Peter,Clapper, Wilma,Jenkinson, Celia,Gunnet, Joseph,Leonard, James,Murray, William V.
supporting information, p. 947 - 952 (2017/09/22)
We have discovered a novel series of isothiazole-based phenylpropanoic acids as GPR120 agonists. Extensive structure-activity relationship studies led to the discovery of a potent GPR120 agonist 4x, which displayed good EC50 values in both calcium and β-arrestin assays. It also presented good pharmaceutical properties and a favorable PK profile. Moreover, it demonstrated in vivo antidiabetic activity in C57BL/6 DIO mice. Studies in WT and knockout DIO mice showed that it improved glucose handling during an OGTT via GPR120. Overall, 4x possessed promising antidiabetic effect and good safety profile to be a development candidate.
Synthesis of a 5-((Aryloxy)methyl)-3-(4-(trifluoromethyl)phenyl)[1,2,4] thiadiazole derivative: A promising PPARα,δ agonist
Reuman, Michael,Hu, Zhiyong,Kuo, Gee-Hong,Li, Xun,Russell, Ronald K.,Shen, Lan,Youells, Scott,Zhang, Yongzheng
, p. 1010 - 1014 (2012/12/30)
The preparation of the PPARα,δ agonist 2-methyl-2-(2-methyl-4- (3-(4-(trifluoromethyl)phenyl)[1,2,4]thiadiazol-5-ylmethoxy)phenoxy)propionic acid sodium salt (17) is described and compared with earlier in-house preparations of this important target compound. Key concerns around a large-scale synthesis of this thiadiazole derivative were a large number of purification steps, the use of dichlorobenzene as a solvent, and a possible large-scale Baeyer-Villiger oxidation. This paper describes a straightforward preparation of the target agonist using methylhydroquinone (MHQ) as an inexpensive precursor that eliminates the need of an oxidation step.
BENZOAZEPIN-OXY-ACETIC ACID DERIVATIVES AS PPAR-DELTA AGONISTS USED FOR THE INCREASE OF HDL-C, LOWER LDL-C AND LOWER CHOLESTEROL
-
Page/Page column 22, (2008/06/13)
The invention is directed to compounds of Formula (I) useful as PPAR agonists. Pharmaceutical compositions and methods of treating one or more conditions including, but not limited to, diabetes, nephropathy, neuropathy, retinopathy, polycystic ovary syndr
Synthesis and identification of [1,2,4]thiadiazole derivatives as a new series of potent and orally active dual agonists of peroxisome proliferator-activated receptors α and δ
Shen, Lan,Zhang, Yan,Wang, Aihua,Sieber-McMaster, Ellen,Chen, Xiaoli,Pelton, Patricia,Xu, Jun Z.,Yang, Maria,Zhu, Peifang,Zhou, Lubing,Reuman, Michael,Hu, Zhiyong,Russell, Ronald,Gibbs, Alan C.,Ross, Hamish,Demarest, Keith,Murray, William V.,Kuo, Gee-Hong
, p. 3954 - 3963 (2008/02/11)
Cardiovascular disease is the most common cause of morbidity and mortality in developed nations. To effectively target dyslipidemia to reduce the risk of cardiovascular disease, it may be beneficial to activate the peroxisome proliferator-activated recept
Substituent effects on15N and13C NMR chemical shifts of 5-phenyl-1,3,4-oxathiazol-2-ones: A theoretical and spectroscopic study
Markgraf, J. Hodge,Hong, Lu,Richardson, David P.,Schofield, Mark H.
, p. 985 - 988 (2008/03/17)
The synthesis and assignment of 15N and 13C NMR signals of the 1,3,4-oxathiazol-2-one ring in a series of para-substituted 5-phenyl derivatives are reported. DFT calculations of 15N and 13C chemical shifts correspond closely to observed values. Substituent effects are interpreted in terms of the Hammett correlation and calculated bond orders. Copyright
4-((Phenoxyalkyl)thio)-phenoxyacetic acids and analogs
-
Page/Page column 16, (2008/06/13)
The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR modulators to treat or inhibit the progression of, for example, dyslipidemia.
