- Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors
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Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy.
- Liu, Bin,Yuan, Xia,Xu, Bo,Zhang, Han,Li, Ridong,Wang, Xin,Ge, Zemei,Li, Runtao
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- Multigram Synthesis of Functionalized Spirocyclic Diazirines
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An approach to the synthesis of spirocyclic diazirines from cyclic ketones was examined on a series of carbo- and heterocyclic substrates containing the amine or carboxylic acid moiety. A mini-library of stereochemically diverse functionalized spirocyclic diazirines was synthesized on a multigram scale with 30–81 % yield.
- Martyloga, Oleksandr V.,Myronenko, Artamon,Tkachenko, Anton M.,Matvienko, Vitalii O.,Kuchkovska, Yuliya O.,Grygorenko, Oleksandr O.
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p. 3744 - 3750
(2019/06/28)
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- Method for the production of O-substituted hydroxylamines
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A new method for the production of O-substituted hydroxylamines is disclosed. Hydroxylamine-O-sulfonic acid is reacted with alkali alkoxide in the presence of a polar aprotic solvent.
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- Antimicrobial 1,3-disubstituted/imidazolium salts
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The imidazolium compounds of the formula STR1 wherein the various substituents are defined hereinbelow and their pharmaceutically acceptable acid addition salts, which possess valuable pharmacological properties are described. In particular, they possess antibacterial, antimycotic, protozoacidal and/or anthelmintic properties and are especially active against parasitic protozoa and worms. The compounds of formula I can be prepared according to known methods.
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