74733-29-2Relevant articles and documents
Palladium-Catalyzed Chlorocarbonylation of Aryl (Pseudo)Halides Through In Situ Generation of Carbon Monoxide
Bismuto, Alessandro,Boehm, Philip,Morandi, Bill,Roediger, Sven
, p. 17887 - 17896 (2020/08/19)
An efficient palladium-catalyzed chlorocarbonylation of aryl (pseudo)halides that gives access to a wide range of carboxylic acid derivatives has been developed. The use of butyryl chloride as a combined CO and Cl source eludes the need for toxic, gaseous carbon monoxide, thus facilitating the synthesis of high-value products from readily available aryl (pseudo)halides. The combination of palladium(0), Xantphos, and an amine base is essential to promote this broadly applicable catalytic reaction. Overall, this reaction provides access to a great variety of carbonyl-containing products through in situ transformation of the generated aroyl chloride. Combined experimental and computational studies support a reaction mechanism involving in situ generation of CO.
A Dual Modulator of Farnesoid X Receptor and Soluble Epoxide Hydrolase to Counter Nonalcoholic Steatohepatitis
Schmidt, Jurema,Rotter, Marco,Weiser, Tim,Wittmann, Sandra,Weizel, Lilia,Kaiser, Astrid,Heering, Jan,Goebel, Tamara,Angioni, Carlo,Wurglics, Mario,Paulke, Alexander,Geisslinger, Gerd,Kahnt, Astrid,Steinhilber, Dieter,Proschak, Ewgenij,Merk, Daniel
supporting information, p. 7703 - 7724 (2017/10/06)
Nonalcoholic steatohepatitis arising from Western diet and lifestyle is characterized by accumulation of fat in liver causing inflammation and fibrosis. It evolves as serious health burden with alarming incidence, but there is no satisfying pharmacological therapy to date. Considering the disease's multifactorial nature, modulation of multiple targets might provide superior therapeutic efficacy. In particular, farnesoid X receptor (FXR) activation that revealed antisteatotic and antifibrotic effects in clinical trials combined with inhibition of soluble epoxide hydrolase (sEH) as anti-inflammatory strategy promises synergies. To exploit this dual concept, we developed agents exerting partial FXR agonism and sEH inhibitory activity. Merging known pharmacophores and systematic exploration of the structure-activity relationship on both targets produced dual modulators with low nanomolar potency. Extensive in vitro characterization confirmed high dual efficacy in cellular context combined with low toxicity, and pilot in vivo data revealed favorable pharmacokinetics as well as engagement on both targets in vivo.
BORON-CONTAINING DIACYLHYDRAZINES
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, (2014/09/29)
The present disclosure provides boron-containing diacylhydrazines having Formula I: and the pharmaceutically acceptable salts and solvates thereof, wherein R1, R2, R3, R4, and R5 are defined as set forth in the specification. The present disclosure also provides the use of boron-containing diacylhydrazines is ecdysone receptor-based inducible gene expression systems. Thus, the present disclosure is useful for applications such as gene therapy, treatment of disease, large scale production of proteins and antibodies, cell-based screening assays, functional genomics, proteomics, metabolomics, and regulation of traits in transgenic organisms, where control of gene expression levels is desirable.