216162-45-7Relevant academic research and scientific papers
Discovery of Novel Thiophene-arylamide Derivatives as DprE1 Inhibitors with Potent Antimycobacterial Activities
Wang, Pengxu,Batt, Sarah M.,Wang, Bin,Fu, Lei,Qin, Rongfei,Lu, Yu,Li, Gang,Besra, Gurdyal S.,Huang, Haihong
, p. 6241 - 6261 (2021/05/06)
In this study, we report the design and synthesis of a series of novel thiophene-arylamide compounds derived from the noncovalent decaprenylphosphoryl-β-d-ribose 2′-epimerase (DprE1) inhibitor TCA1 through a structure-based scaffold hopping strategy. Systematic optimization of the two side chains flanking the thiophene core led to new lead compounds bearing a thiophene-arylamide scaffold with potent antimycobacterial activity and low cytotoxicity. Compounds 23j, 24f, 25a, and 25b exhibited potent in vitro activity against both drug-susceptible (minimum inhibitory concentration (MIC) = 0.02-0.12 μg/mL) and drug-resistant (MIC = 0.031-0.24 μg/mL) tuberculosis strains while retaining potent DprE1 inhibition (half maximal inhibitory concentration (IC50) = 0.2-0.9 μg/mL) and good intracellular antimycobacterial activity. In addition, these compounds showed good hepatocyte stability and low inhibition of the human ether-à-go-go related gene (hERG) channel. The representative compound 25a with acceptable pharmacokinetic property demonstrated significant bactericidal activity in an acute mouse model of tuberculosis. Moreover, the molecular docking study of template compound 23j provides new insight into the discovery of novel antitubercular agents targeting DprE1.
Diaryl 2- amide-substituted thiophene imide ester compound as well as preparation method and application thereof (by machine translation)
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Paragraph 0159; 0335; 0339-0341, (2020/02/17)
The invention also discloses a 2 - synthesis method thereof, and an application of the compound as an antibacterial agent, in the phthisis-caused by the bacterium, in particular to the, mycobacterium-induced infectious disease (especially (Tuberculosis,TB), mycobacterium- induced mycobacterium, tuberculosis), and (I) the invention, specifically relates to a pharmaceutical composition containing the compound of the present invention or, a R pharmaceutical composition comprising the compound of the present invention. 1 , R2 , R3 , R4 , R5 As described Y in the present invention. as described in the specification, the present invention is directed, to the preparation of novel compounds, having an anti-mycobacterial activity as potential, new drug (s) for the treatment (TB) or preventative treatment of infectious diseases, consisting of M. tuberculosis, in particular phthisis- caused by tubercular mycobacteria, while being useful in overcoming the problems associated with drug resistance. (by machine translation)
Rhodium(III)-Catalyzed Redox-Neutral Coupling of α-Trifluoromethylacrylic Acid with Benzamides through Directed C?H Bond Cleavage
Yoshimoto, Risa,Usuki, Yoshinosuke,Satoh, Tetsuya
supporting information, p. 802 - 806 (2020/02/25)
A rhodium(III)-catalyzed redox-neutral coupling of α-trifluoromethylacrylic acid with bezamides proceeds smoothly accompanied by amide-directed C?H bond cleavage to produce β-[2-(aminocarbonyl)phenyl]-α-trifluoromethylpropanoic acid derivatives. One of th
Synthesis of CF3-containing isoindolinone derivatives through rhodium-catalyzed oxidative coupling of benzamides with 2-trifluoromethylacrylate
Yoshimoto, Risa,Morisaka, Hideaki,Usuki, Yoshinosuke,Shibata, Yu,Tanaka, Ken,Satoh, Tetsuya
supporting information, p. 1481 - 1483 (2020/12/31)
The oxidative coupling of benzamides with methyl 2- trifluoromethylacrylate proceeds smoothly under rhodium(III) catalysis to produce trifluoromethyl-substituted isoindolinone derivatives. The catalyst system [CpERhCl2]2/AgSbF6 is effective for the oxidat
Solid-supported hydrazone of 4-(4′-Formyl-3′-methoxyphenoxy)butyric acid as a new traceless linker for solid-phase synthesis
Okorochenkov, Sergei,Burglova, Kristyna,Popa, Igor,Hlavac, Jan
supporting information, p. 180 - 183 (2015/01/30)
The use of a hydrazine derived from a backbone amide linker as a new hydrazone-based traceless linker for solid-phase organic synthesis is described. The stability of the linker was tested under various conditions, including treatment with acids, bases, and borohydrides. Final compounds can be released by selective cleavage using trimethylsilanolate. To demonstrate the versatility of the linker, the synthesis of a model compound under various reaction conditions was performed with good results.
