383-13-1Relevant academic research and scientific papers
Second-Generation Dual FXR/sEH Modulators with Optimized Pharmacokinetics
Helmst?dter, Moritz,Kaiser, Astrid,Brunst, Steffen,Schmidt, Jurema,Ronchetti, Riccardo,Weizel, Lilia,Proschak, Ewgenij,Merk, Daniel
supporting information, p. 9525 - 9536 (2021/07/20)
Non-alcoholic steatohepatitis (NASH) presents as an epidemic chronic liver disease that is closely associated with metabolic disorders and involves hepatic steatosis, inflammation, and fibrosis as key factors. Despite the enormous global prevalence of NASH, effective pharmacological interventions are lacking. Based on the hypothesis that the multifactorial condition NASH may benefit from combined multiple modes of action for enhanced therapeutic efficacy, we have previously developed dual FXR activators/sEH inhibitors (FXRa/sEHi) and observed remarkable antifibrotic effects upon their use in rodent NASH models. However, these first-generation FXRa/sEHi were characterized by moderate metabolic stability and short in vivo half-life. Aiming to overcome these pharmacokinetic drawbacks, we have systematically studied the structure-activity and structure-stability relationships of the chemotype and obtained second-generation FXRa/sEHi with improved pharmacokinetic parameters. With high plasma exposure, a half-life greater than 5 h, and similar dual potency on the intended targets, 13 presents as a substantially optimized FXRa/sEHi for late-stage preclinical development.
The solid complex Zn(CF3)Br·2DMF as an alternative reagent for the preparation of both, trifluoromethyl and pentafluoroethyl copper, CuCF3 and CuC2F5
Kremlev, Mikhail M.,Tyrra, Wieland,Mushta, Aleksej I.,Naumann, Dieter,Yagupolskii, Yurii L.
experimental part, p. 212 - 216 (2010/04/30)
Trifluoromethylcopper and pentafluoroethylcopper are prepared conveniently via the reaction of the solid complex Zn(CF3)Br·2DMF with copper(I) bromide in N,N-dimethylformamide. The reactions of both copper species with 2,4-dinitrochlorobenzene,
Heteroaryl and benzyl amide compounds
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Page/Page column 9, (2010/11/28)
Compounds of formula I wherein R1, R2, R4, R5, A, B, D and n are as defined, and pharmaceutically acceptable salts thereof, processes for their preparation, their use as pharmaceuticals and pharmaceutical compositions comprising them.
