Schiffler, Matthew A.; Antonysamy, Stephen; Bhattachar, Shobha N.; Campanale, Kristina M.; Chandrasekhar, Srinivasan; Condon, Bradley; Desai, Prashant V.; Fisher, Matthew J.; Groshong, Christopher; Harvey, Anita; Hickey, Michael J.; Hughes, Norman E.; Jones, Scott A.; Kim, Euibong J.; Kuklish, Steven L.; Luz, John G.; Norman, Bryan H.; Rathmell, Richard E.; Rizzo, John R.; Seng, Thomas W.; Thibodeaux, Stefan J.; Woods, Timothy A.; York, Jeremy S.; Yu, Xiao-Peng published an article on January 14 ,2016. The article was titled 《Discovery and Characterization of 2-Acylaminoimidazole Microsomal Prostaglandin E Synthase-1 Inhibitors》, and you may find the article in Journal of Medicinal Chemistry.Application In Synthesis of 5-Chloro-2-(trifluoromethyl)benzoic acid The information in the text is summarized as follows:
As part of a program aimed at the discovery of antinociceptive therapy for inflammatory conditions, a screening hit was found to inhibit microsomal prostaglandin E synthase-1 (mPGES-1) with an IC50 of 17.4 μM. Structural information was used to improve enzyme potency by over 1000-fold. Addition of an appropriate substituent alleviated time-dependent cytochrome P 450 3A4 (CYP3A4) inhibition. Further structure-activity relationship (SAR) studies led to 8, which had desirable potency (IC50 = 12 nM in an ex vivo human whole blood (HWB) assay) and absorption, distribution, metabolism, and excretion (ADME) properties. Studies on the formulation of 8 identified 8·H3PO4 as suitable for clin. development. Omission of a lipophilic portion of the compound led to 26, a readily orally bioavailable inhibitor with potency in HWB comparable to celecoxib. Furthermore, 26 was selective for mPGES-1 inhibition vs. other mechanisms in the prostanoid pathway. These factors led to the selection of 26 as a second clin. candidate. The results came from multiple reactions, including the reaction of 5-Chloro-2-(trifluoromethyl)benzoic acid(cas: 654-98-8Application In Synthesis of 5-Chloro-2-(trifluoromethyl)benzoic acid)
5-Chloro-2-(trifluoromethyl)benzoic acid(cas: 654-98-8) belongs to organochlorine compounds. Many organochlorine compounds have been isolated from natural sources ranging from bacteria to humans. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Application In Synthesis of 5-Chloro-2-(trifluoromethyl)benzoic acid
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics