5577-42-4Relevant articles and documents
Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators
Li, Ridong,Ning, Xianling,Zhou, Shuo,Lin, Zhiqiang,Wu, Xingyu,Chen, Hong,Bai, Xinyu,Wang, Xin,Ge, Zemei,Li, Runtao,Yin, Yuxin
, p. 48 - 65 (2017/11/23)
Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti-proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 μM to 0.81 μM against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies.
Asymmetric reduction of N-[4-(2-bromoacetyl)phenyl]methanesulfonamide by employing Candida viswanathii MTCC 5158
Meena, Kamlesh,Ravi
experimental part, p. 1316 - 1318 (2012/09/07)
Enantioselective synthesis of chiral drugs by chemoenzymatic processes have attracted attention in which the crucial stereogenic step involves an enzymatic reaction by virtue of chemo-, regio- and enantio- selectivity and eco-friendly nature of biocatalysis, (S)-sotalol a β-blocker, belongs to class-III antiarrhythmic agents. To avoid the side effects of racemic sotalol, efforts have been put forward to synthesize a key intermediate for the synthesis of (S)-enantiomer of sotalol, which is more potent than the (R)-enantiomer. The aryl ketone, N-(4-acetyl-phenyl) methanesulfonamide was synthesized from the initial substrate 4-aminoacetophenone. Further, the bromination of aryl ketone was carried out to obtain N-[4-(2-bromo-acetyl)-phenyl]-methanesulfonamide. The chemical reduction as well as biological reduction of aryl ketone was carried out to obtain a racemate alcohol N [4-(2-bromo-1-hydroxy-ethyl) (4-methanesulfonamide)]ethanol and chiral (S)-N-[4-(2-bromo-1-hydroxy-ethyl)(4- methanesulfonamide)]ethanol, respectively. (S)-N-[-4-(2-bromo-1-hydroxy-ethyl) (4- methanesulfonamide)]ethanol is a key intermediate for the synthesis of (S)-sotalol. The biological reduction was carried out by using whole cells and found that 96 % conversion was obtained at 12th h of reaction after that the percentage conversion decreased.
Pyrrole derivatives and medicinal composition
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, (2008/06/13)
The invention relates to a pharmaceutical composition comprising a pyrrole derivative of the following formula [1] or a pharmaceutically acceptable salt thereof, or a solvate of either of them, as an active ingredient. STR1 (wherein R1 represents hydrogen or alkoxycar91 bonylamino, R2 represents alkyl, aryl which may be substituted, aromatic heterocyclyl which may be substituted, unsubstituted amino, monoalkylamino, dialkylamino, or cyclic amino which may be substituted; R3 represents cyano or carbamoyl; R4 represents hydrogen or alkyl; E represents alkylene; q is equal to 0 or 1, A represents methyl, aryl which may be substituted, or aromatic heterocyclyl which may be substituted). The pharmaceutical composition of the invention is effective for the treatment of pollakiuria or urinary incontinence.
