945401-04-7Relevant academic research and scientific papers
Synthesis and anticancer activity of novel bisindolylhydroxymaleimide derivatives with potent GSK-3 kinase inhibition
Winfield, Hannah J.,Cahill, Michael M.,O'Shea, Kevin D.,Pierce, Larry T.,Robert, Thomas,Ruchaud, Sandrine,Bach, Stéphane,Marchand, Pascal,McCarthy, Florence O.
supporting information, p. 4209 - 4224 (2018/07/21)
Synthesis and biological evaluation of a series of novel indole derivatives as anticancer agents is described. A bisindolylmaleimide template has been derived as a versatile pharmacophore with which to pursue chemical diversification. Starting from maleimide, the introduction of an oxygen to the headgroup (hydroxymaleimide) was initially investigated and the bioactivity assessed by screening of kinase inhibitory activity, identifying substituent derived selectivity. Extension of the hydroxymaleimide template to incorporate substitution of the indole nitrogens was next completed and assessed again by kinase inhibition identifying unique selectivity patterns with respect to GSK-3 and CDK kinases. Subsequently, the anticancer activity of bisindolylmaleimides were assessed using the NCI-60 cell screen, disclosing the discovery of growth inhibitory profiles towards a number of cell lines, such as SNB-75 CNS cancer, A498 and UO-31 renal, MDA MB435 melanoma and a panel of leukemia cell lines. The potential for selective kinase inhibition by modulation of this template is evident and will inform future selective clinical candidates.
Synthesis and biological evaluation of benzothiazole incorporated 1-phenylsulfonylindole-3-acetamide derivatives
Sharma, Prince P.,Roy, Ram K.,Anurag,Verma, Krishan
, p. 2878 - 2880 (2012/07/28)
Indole-3-acetic acid was esterified to give methyl ester (2), which was treated with substituted aromatic sulphonyl chloride in alkaline media to give 2-[1-(phenyl sufonyl-1H-indole-3-yl]methyl acetate (3). Further the compound 3 was converted to acid (4). Finally compound 4 was coupled with 6-substituted benzothiazole-2-amines by means of EDC to give acetamide derivatives (5a-i). The structures of the newly synthesized compounds have been established by analytical and spectral methods. These compounds have also been screened for analgesic activity.
[11C]Enzastaurin, the first design and radiosynthesis of a new potential PET agent for imaging of protein kinase C
Wang, Min,Xu, Lu,Gao, Mingzhang,Miller, Kathy D.,Sledge, George W.,Zheng, Qi-Huang
experimental part, p. 1649 - 1653 (2011/05/11)
Enzastaurin (LY317615) is a potent and selective protein kinase C (PKC) inhibitor with an IC50 value of ～6 nM. [11C] Enzastaurin (3-(1-[11C]methyl-1H-indol-3-yl)-4-[1-[1-(2- pyridinylmethyl)-4-piperidinyl]-1H-indol-3-yl]-1H-pyrrole-2,5-dione), a new potential PET agent for imaging of PKC, was first designed and synthesized in 20-25% decay corrected radiochemical yield and 370-555 GBq/μmol specific activity at end of bombardment (EOB). The synthetic strategy was to prepare a carbon-11-labeled maleic anhydride intermediate followed by the conversion to maleimide.
Synthesis of a novel N-nitroalkyl bisindolylmaleimide
Roy, Sudipta,Gribble, Gordon W.
, p. 1879 - 1886 (2008/02/03)
We describe the synthesis of the novel N-nitropropyl bisindolylmaleimide 6. Copyright Taylor & Francis Group, LLC.
A Facile Synthesis of 3-Substituted Indoles
Nagarathnam, Dhanapalan
, p. 953 - 958 (2007/10/02)
1-Benzoyl-3-bromomethylindole (2a) or 1-benzenesulfonyl-3-bromomethylindole (2b) reacts with C, N, O, and P-containing nucleophiles to give potential intermediates for the synthesis of a wide range of indole alkaloids and pharmacologically important substances, in good to excellent yields.
