51-08-1Relevant articles and documents
Comparative study of dG affinity vs. DNA methylation modulating properties of side chain derivatives of procainamide: Insight into its DNA hypomethylating effect
Gawade,Chakravarty,Debgupta,Sangtani,Narwade,Gonnade,Puranik,Deobagkar
, p. 5350 - 5358 (2016/02/05)
Procainamide derivatives have been synthesized to investigate the role of side chains in modulating the DNA methylation level in cancer cells and gain insight into its mechanism of action. The synthesized derivatives comprised of flexible (dimethyl), cons
A platinum(ii) phenylphenanthroimidazole with an extended side-chain exhibits slow dissociation from a c-kit G-quadruplex motif
Castor, Katherine J.,Liu, Zhaomin,Fakhoury, Johans,Hancock, Mark A.,Mittermaier, Anthony,Moitessier, Nicolas,Sleiman, Hanadi F.
, p. 17836 - 17845 (2014/01/17)
A series of three platinum(II) phenanthroimidazoles each containing a protonable side-chain appended from the phenyl moiety through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) were evaluated for their capacities to bind to human telomere, c-Myc, and c-Kit derived G-quadruplexes. The side-chain has been optimized to enable a multivalent binding mode to G-quadruplex motifs, which would potentially result in selective targeting. Molecular modeling, high-throughput fluorescence intercalator displacement (HT-FID) assays, and surface plasmon resonance (SPR) studies demonstrate that complex 2 exhibits significantly slower dissociation rates compared to platinum phenanthroimidazoles without side-chains and other reported G-quadruplex binders. Complex 2 showed little cytotoxicity in HeLa and A172 cancer cell lines, consistent with the fact that it does not follow a telomere-targeting pathway. Preliminary mRNA analysis shows that 2 specifically interacts with the ckit promoter region. Overall, this study validates 2 as a useful molecular probe for c-Kit related cancer pathways. Bound to impress: A series of three platinum(II) phenanthroimidazoles each containing a protonable side-chain appended from the phenyl moiety through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), was evaluated for their capacity to bind to human telomere, c-Myc, and c-Kit derived G-quadruplexes (see scheme). The presence of the side-chain enables a multivalent binding mode to G-quadruplex motifs. Copyright
Development of o-chlorophenyl substituted pyrimidines as exceptionally potent aurora kinase inhibitors
Lawrence, Harshani R.,Martin, Mathew P.,Luo, Yunting,Pireddu, Roberta,Yang, Hua,Gevariya, Harsukh,Ozcan, Sevil,Zhu, Jin-Yi,Kendig, Robert,Rodriguez, Mercedes,Elias, Roy,Cheng, Jin Q.,Sebti, Sa?d M.,Schonbrunn, Ernst,Lawrence, Nicholas J.
, p. 7392 - 7416 (2012/11/07)
The o-carboxylic acid substituted bisanilinopyrimidine 1 was identified as a potent hit (Aurora A IC50 = 6.1 ± 1.0 nM) from in-house screening. Detailed structure-activity relationship (SAR) studies indicated that polar substituents at the para position of the B-ring are critical for potent activity. X-ray crystallography studies revealed that compound 1 is a type I inhibitor that binds the Aurora kinase active site in a DFG-in conformation. Structure-activity guided replacement of the A-ring carboxylic acid with halogens and incorporation of fluorine at the pyrimidine 5-position led to highly potent inhibitors of Aurora A that bind in a DFG-out conformation. B-Ring modifications were undertaken to improve the solubility and cell permeability. Compounds such as 9m with water-solubilizing moieties at the para position of the B-ring inhibited the autophosphorylation of Aurora A in MDA-MB-468 breast cancer cells.
Design, synthesis, and biological evaluation of novel water-soluble N-mustards as potential anticancer agents
Kapuriya, Naval,Kakadiya, Rajesh,Dong, Huajin,Kumar, Amit,Lee, Pei-Chih,Zhang, Xiuguo,Chou, Ting-Chao,Lee, Te-Chang,Chen, Ching-Huang,Lam, King,Marvania, Bhavin,Shah, Anamik,Su, Tsann-Long
experimental part, p. 471 - 485 (2011/02/27)
A series of novel water-soluble N-mustard-benzene conjugates bearing a urea linker were synthesized. The benzene moiety contains various hydrophilic side chains are linked to the meta- or para-position of the urea linker via a carboxamide or an ether link
NOVEL CARBOXAMIDE COMPOUNDS FOR USE IN MCH RECEPTOR RELATED DISORDERS
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Page/Page column 43, (2008/06/13)
Novel compounds of formula (I) which modulate MCH activity are disclosed, in which A is a linker; B is a connecting moiety; Ar1 and Ar2 are aryl or heteroaryl groups; R1 and R2 are hydrogen, halogen atoms, CF3, OCF3/