937367-26-5Relevant articles and documents
IRAK DEGRADERS AND USES THEREOF
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Paragraph 2350; 2351, (2019/07/10)
The present invention provides compounds, compositions thereof, and methods of using the same.
Synthesis and biological evaluation of the first dual tyrosyl-DNA phosphodiesterase i (Tdp1)-topoisomerase i (Top1) inhibitors
Nguyen, Trung Xuan,Morrell, Andrew,Conda-Sheridan, Martin,Marchand, Christophe,Agama, Keli,Bermingam, Alun,Stephen, Andrew G.,Chergui, Adel,Naumova, Alena,Fisher, Robert,O'Keefe, Barry R.,Pommier, Yves,Cushman, Mark
scheme or table, p. 4457 - 4478 (2012/08/07)
Substances with dual tyrosyl-DNA phosphodiesterase I-topoisomerase I inhibitory activity in one low molecular weight compound would constitute a unique class of anticancer agents that could potentially have significant advantages over drugs that work against the individual enzymes. The present study demonstrates the successful synthesis and evaluation of the first dual Top1-Tdp1 inhibitors, which are based on the indenoisoquinoline chemotype. One bis(indenoisoquinoline) had significant activity against human Tdp1 (IC 50 = 1.52 ± 0.05 μM), and it was also equipotent to camptothecin as a Top1 inhibitor. Significant insights into enzyme-drug interactions were gained via structure-activity relationship studies of the series. The present results also document the failure of the previously reported sulfonyl ester pharmacophore to confer Tdp1 inhibition in this indenoisoquinoline class of inhibitors even though it was demonstrated to work well for the steroid NSC 88915 (7). The current study will facilitate future efforts to optimize dual Top1-Tdp1 inhibitors.
OXOBENZINDOLIZINOQUINOLINES AND USES THEREOF
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Page/Page column 42, (2009/12/23)
The synthesis of aromathecins, substituted 12H-5,l la-diazadibenzo[b,h]fluoren- 11 -ones is described. Use of these cytotoxic compounds and pharmaceutical compositions containing them for the treatment of cancer is described. Two novel processes for the synthesis of this system and a series of 14-substituted aromathecins as novel cytotoxic, topoisomerase I poisons are described.
Synthesis and biological evaluation of 14-(aminoalkyl-aminomethyl)aromathecins as topoisomerase I inhibitors: Investigating the hypothesis of shared structure-activity relationships
Cinelli, Maris A.,Cordero, Brenda,Dexheimer, Thomas S.,Pommier, Yves,Cushman, Mark
experimental part, p. 7145 - 7155 (2010/03/01)
The aromathecin topoisomerase I (top1) inhibitors offer promising scaffolds for the development of novel cancer chemotherapeutics. They are 'composites' of the camptothecin and indenoisoquinoline top1 inhibitors. Interestingly, some structure-activity relationship (SAR) overlap between the aromathecins and the indenoisoquinolines has been observed. For both classes, placement of certain polar groups in similar regions of the heteroaromatic system improves top1 inhibitory and antiproliferative activities. A series of water-soluble aromathecins substituted at position 14 with diaminoalkanes of various lengths has been prepared. These compounds all possess similar antiproliferative potency, but a general trend is observed: aromathecins with longer diaminoalkane substituents (>6 carbons) possess lower anti-top1 activity than their smaller counterparts (2-4 carbons), presumably as a result of unfavorable hydrophobic interactions. This trend is also noted with the indenoisoquinolines, revealing additional SAR overlap that supports the hypothesis that there is a 'universal' top1 inhibitor SAR.
N-SUBSTITUTED INDENOISOQUINOLINES AND SYNTHESES THEREOF
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Page/Page column 40, (2008/06/13)
N-Substituted indenoisoquinoline compounds, and pharmaceutical formulations of N-substituted indenoisoquinoline compounds are described. Also described are processes for preparing N-substituted indenoisoquinoline compounds. Also described are methods for
Investigation of the lactam side chain length necessary for optimal indenoisoquinoline topoisomerase I inhibition and cytotoxicity in human cancer cell cultures
Morrell, Andrew,Placzek, Michael S.,Steffen, Jamin D.,Antony, Smitha,Agama, Keli,Pommier, Yves,Cushman, Mark
, p. 2040 - 2048 (2008/02/01)
Indenoisoquinolines with lactam substituents such as ethylamino, propylamino, and butylamino have previously demonstrated potent biological activity, but an optimal length has never been established. In the present study, a series of simplified indenoisoquinoline analogues possessing a linker spacing of 0-12 carbon atoms between the lactam nitrogen and the terminal amino group have been prepared, determining that 2-4-atom lengths are optimal for topoisomerase I inhibition and cytotoxicity. Using these lengths, analogues were prepared with the amino group and portions of the linker replaced by a pyridine ring. A three-carbon spacer within the pyridine series still demonstrated potent topoisomerase I inhibition.
ALIPHATIC PYRAZINOYLGUANIDINE SODIUM CHANNEL BLOCKERS WITH BETA AGONIST ACTIVITY
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Page/Page column 52, (2010/11/29)
The present invention provides sodium channel blockers possessing beta-adrenergic receptor agonist activity.
PHENYL SUBSTITUTED PYRAZINOYLGUANIDINE SODIUM CHANNEL BLOCKERS POSSESSING BETA AGONIST ACTIVITY
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Page/Page column 52; 85, (2008/06/13)
The present invention relates to sodium channel blockers. The present invention also includes a variety of methods of treatment using these inventive sodium channel blockers.
COMB COPOLYMERS WITH THERMOTROPIC AND LYOTROPIC PROPERTIES SYNTHESIS AND STRUCTURAL STUDY
Gallot, Bernard,Douy, Andre
, p. 367 - 374 (2007/10/02)
Comb copolymers with polyacrylamide or polymethacrylamide main chains and lipopeptidic side chains were synthesized in two steps: synthesis of a polymerizable lipopeptide followed by radical polymerization of the lipopeptidic macromonomer.X ray diffraction and DSC studies showed that comb copolymers exhibit both a thermotropic and a lyotropic behaviour.The influence of the nature and the degree of polymerization of the peptidic chains on the type (smectic, nematic or cholesteric) and the domain of stability of the liquid-crystalline structures was established.In the case of smectic structures, the influence of the solvent concentration and the degree of polymerization of the peptidic chains on the distances between the smectic planes was also established.
