232275-49-9Relevant articles and documents
Definitive Metabolite Identification Coupled with Automated Ligand Identification System (ALIS) Technology: A Novel Approach to Uncover Structure-Activity Relationships and Guide Drug Design in a Factor IXa Inhibitor Program
Zhang, Ting,Liu, Yong,Yang, Xianshu,Martin, Gary E.,Yao, Huifang,Shang, Jackie,Bugianesi, Randal M.,Ellsworth, Kenneth P.,Sonatore, Lisa M.,Nizner, Peter,Sherer, Edward C.,Hill, Susan E.,Knemeyer, Ian W.,Geissler, Wayne M.,Dandliker, Peter J.,Helmy, Roy,Wood, Harold B.
, p. 1818 - 1829 (2016)
A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinities to the FIXa protein. Microgram quantities of the metabolites of interest were then isolated through microisolation analytical capabilities, and structurally characterized using MicroCryoProbe heteronuclear 2D NMR techniques. The isolated metabolites recovered from the NMR experiments were then submitted directly to an in vitro FIXa enzymatic assay. The order of the metabolites' binding affinity to the Factor IXa protein from the ALIS assay was completely consistent with the enzymatic assay results. This work showcases an innovative and efficient approach to uncover structure-activity relationships (SARs) and guide drug design via microisolation-structural characterization and ALIS capabilities.
A kind of the second aryl amine derivative and its preparation method, pharmaceutical composition and use thereof
-
, (2017/08/30)
The invention provides diarylamide type derivatives having a structure shown as a formula (I) as follows, or pharmaceutically acceptable salts thereof, a preparing method of the derivatives, compositions containing the derivatives and the pharmaceutically acceptable salts, and medicine uses of the derivatives and the pharmaceutically acceptable salts. The diarylamide type derivatives having the structure shown as the formula (I) or the pharmaceutically acceptable salts thereof have antagonistic effects on FXR. Integral animal experiments show that the compounds have effects of decreasing blood sugar and reducing blood fat. The compounds can be used for treating hyperlipidemia and type 2 diabetes mellitus.
Preparation of fluorous Yamaguchi reagents and evaluation of their reactivity in esterification
Nishio, Yuya,Kawazu, Akari,Hirano, Shun,Matsubara, Hiroshi
supporting information, p. 720 - 725 (2016/01/15)
Fluorous Yamaguchi (FY) reagents bearing a perfluoroalkyl chain were prepared and employed in esterification reactions; the yields were similar to those obtained with the traditional Yamaguchi (TY) reagent. Fluorous benzoic acids derived from the FY reagents were separated easily after the reaction. GC analysis revealed that the initial rates of reaction with the FY reagents were higher than those with the TY reagent. The acidities of benzoic acids produced from the FY and TY reagents were predicted by DFT to be similar (1.20 and 0.96, respectively).
