6192-01-4Relevant articles and documents
New 8-Nitroquinolinone Derivative Displaying Submicromolar in Vitro Activities against Both Trypanosoma brucei and cruzi
Bergé, Justine,Bonduelle, Colin,Boudot, Clotilde,Bourgeade-Delmas, Sandra,Boutet-Robinet, Elisa,Brossas, Jean-Yves,Corvaisier, Sophie,Courtioux, Bertrand,Deraeve, Céline,Destere, Alexandre,Fairlamb, Alan H.,Malzert-Fréon, Aurélie,Mazier, Dominique,Milne, Rachel,Paris, Luc,Pedron, Julien,Pinault, Emilie,Pratviel, Geneviève,Since, Marc,Sournia-Saquet, Alix,Stigliani, Jean-Luc,Tronnet, Antoine,Valentin, Alexis,Verhaeghe, Pierre,Wyllie, Susan
supporting information, p. 464 - 472 (2020/04/30)
An antikinetoplastid pharmacomodulation study was conducted at position 6 of the 8-nitroquinolin-2(1H)-one pharmacophore. Fifteen new derivatives were synthesized and evaluated in vitro against L. infantum, T. brucei brucei, and T. cruzi, in parallel with a cytotoxicity assay on the human HepG2 cell line. A potent and selective 6-bromo-substituted antitrypanosomal derivative 12 was revealed, presenting EC50 values of 12 and 500 nM on T. b. brucei trypomastigotes and T. cruzi amastigotes respectively, in comparison with four reference drugs (30 nM ≤ EC50 ≤ 13 μM). Moreover, compound 12 was not genotoxic in the comet assay and showed high in vitro microsomal stability (half life >40 min) as well as favorable pharmacokinetic behavior in the mouse after oral administration. Finally, molecule 12 (E° = -0.37 V/NHE) was shown to be bioactivated by type 1 nitroreductases, in both Leishmania and Trypanosoma, and appears to be a good candidate to search for novel antitrypanosomal lead compounds.
INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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Page/Page column 333, (2018/06/30)
Compounds of formula (I') and methods of their use and preparation, as well as compositions comprising compounds of formula (I').
Enantioselective Synthesis of N?H-Free 1,5-Benzothiazepines
Wang, Guojin,Tang, Yu,Zhang, Yu,Liu, Xiaohua,Lin, Lili,Feng, Xiaoming
supporting information, p. 554 - 557 (2017/01/18)
An enantioselective sulfa-Michael-cyclization reaction was developed for the synthesis of 1,5-benzothiazepines with versatile pharmacological activities. The reaction between 2-aminothiophenol and α,β-unsaturated pyrazoleamides gave direct access to N?H-free 1,5-benzothiazepines in the presence of a chiral N,N′-dioxide/Yb(OTf)3complex. Excellent enantioselectivities (up to 96 % ee) and high yields (up to 99 %) were obtained for a broad range of substrates under mild reaction conditions. This method provided a facile approach to the antidepressant drug (R)-(?)-Thiazesim.
