- Synthesis and biological evaluation of ethacrynic acid derivatives bearing sulfonamides as potent anti-cancer agents
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A series of ethacrynic acid (2-[2,3-dichloro-4-(2-methylidenebutanoyl)phenoxy]acetic acid) (EA, Edecrin) containing sulfonamides linked via three types of linkers namely 1,2-ethylenediamine, piperazine and 4-aminopiperidine was synthesized and subsequently evaluated in vitro against HL60 and HCT116 cancer cell lines. All the EA analogs, excluding 6a and 6c, showed anti-proliferative activity with IC50s in the micromolar range (less than 4 uM). Three derivatives 6b, 7b and 7e were selected for their interesting dual activity on HL60 cell line in order to be further evaluated against a panel of cancer cell lines (HCT116, A549, MCF7, PC3, U87-MG and SKOV3) as well as on MRC5 as a normal cell line. These compounds displayed IC50 values in nanomolar range against A549, MCF7, PC3 and HCT116 cell lines, deducing the discovery that piperazine or 4-aminopiperidine is the linker's best choice to develop EA analogs with highly potent anti-proliferative activities own up to 24 nM. Besides, in terms of selectivity, those linkers are more suitable offering safety ratios of up to 63.8.
- Bignon, Jér?me,El Abbouchi, Abdelmoula,El Brahmi, Nabil,El Kazzouli, Sa?d,Guillaumet, Gérald,Hiebel, Marie-Aude,Suzenet, Franck
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supporting information
(2020/08/07)
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- HETEROCYCLIC COMPOUND
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The present invention provides to a compound having melanin-concentrating hormone receptor antagonistic action and low toxicity, and useful as a agent for the prophylaxis or treatment of obesity and the like. The present invention relates to a compound re
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Page/Page column 44-45
(2010/12/30)
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- PYRAZOLE DERIVATIVES FOR THE INHIBITION OF CDK' S AND GSK' S
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The invention provides compounds of the formula (I), or salts, tautomers, N-oxides or solvates thereof wherein: R1 is selected from: (a) 2,6-dichlorophenyl; (b) 2,6-difluorophenyl; (c) a 2,3,6-trisubstituted phenyl group wherein the substituents for the phenyl group are selected from fluorine, chlorine, methyl and methoxy; (d) a group R0; (e) a group R a; (f) a group Rlb; (g) a group Rlc; (h) a group Rld; and 0) 2,6-difluorophenylamino ; wherein R )0υ, r R> llaa, T Rj I1bD, T R) I1cC, r R> Iidα, r R?2zaa, r R>22bD and RJ are as defined in the claims. The compounds have activity as inhibitors of cdk kinase (such as cdkl or cdk2) and glycogen synthase kinase-3 activity.
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Page/Page column 164
(2008/06/13)
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