4457-32-3Relevant articles and documents
In vitro radical scavenging and cytotoxic activities of novel hybrid selenocarbamates
Romano, Beatriz,Plano, Daniel,Encío, Ignacio,Palop, Juan Antonio,Sanmartín, Carmen
, p. 1716 - 1727 (2015/03/30)
Novel selenocyanate and diselenide derivatives containing a carbamate moiety were synthesised and evaluated in vitro to determine their cytotoxic and radical scavenging properties. Cytotoxic activity was tested against a panel of human cell lines including CCRF-CEM (lymphoblastic leukaemia), HT-29 (colon carcinoma), HTB-54 (lung carcinoma), PC-3 (prostate carcinoma), MCF-7 (breast adenocarcinoma), 184B5 (non-malignant, mammary gland derived) and BEAS-2B (non-malignant, derived from bronchial epithelium). Most of the compounds displayed high antiproliferative activity with GI50 values below 10 μM in MCF-7, CCRF-CEM and PC-3 cells. Radical scavenging properties of the new selenocompounds were confirmed testing their ability to scavenge DPPH and ABTS radicals. Based on the activity of selenium-based glutathione peroxidases (GPxs), compounds 1a, 2e and 2h were further screened for their capacity to reduce hydrogen peroxide under thiol presence. Results suggest that compound 1a mimics GPxs activity. Cytotoxic parameters, radical scavenging activity and ADME profile point to 1a as promising drug candidate.
SAR development of lysine-based irreversible inhibitors of transglutaminase 2 for huntington's disease
Wityak, John,Prime, Michael E.,Brookfield, Frederick A.,Courtney, Stephen M.,Erfan, Sayeh,Johnsen, Siw,Johnson, Peter D.,Li, Marie,Marston, Richard W.,Reed, Laura,Vaidya, Darshan,Schaertl, Sabine,Pedret-Dunn, Anna,Beconi, Maria,MacDonald, Douglas,Mu?oz-Sanjuan, Ignacio,Dominguez, Celia
supporting information, p. 1024 - 1028 (2013/02/22)
We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling and in vitro ADME properties of selected compounds are also reported.
Synthesis and structure-activity relationships of nitrobenzyl phosphoramide mustards as nitroreductase-activated prodrugs
Hu, Longqin,Wu, Xinghua,Han, Jiye,Chen, Lin,Vass, Simon O.,Browne, Patrick,Hall, Belinda S.,Bot, Christopher,Gobalakrishnapillai, Vithurshaa,Searle, Peter F.,Knox, Richard J.,Wilkinson, Shane R.
body text, p. 3986 - 3991 (2011/08/06)
A series of nitrobenzyl phosphoramide mustards and their analogs was designed and synthesized to explore their structure-activity relationships as substrates of nitroreductases from Escherichia coli and trypanosomes and as potential antiproliferative and antiparasitic agents. The position of the nitro group on the phenyl ring was important with the 4-nitrobenzyl phosphoramide mustard (1) offering the best combination of enzyme activity and antiproliferative effect against both mammalian and trypanosomatid cells. A preference was observed for halogen substitutions ortho to benzyl phosphoramide mustard but distinct differences were found in their SAR of substituted 4-nitrobenzyl phosphoramide mustards in E. coli nitroreductase-expressing cells and in trypanosomatids expressing endogenous nitroreductases.
NOVEL VINBLASTINE DERIVATIVES, THEIR PREPARATION, USE AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAID DERIVATIVES
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Page/Page column 49, (2009/12/05)
The invention provides vinblastine derivatives represented by the following formula 1 or their physiologically acceptable salts, their preparation, use and pharmaceutical compositions comprising the said derivatives. The said vinblastine derivatives show inhibiting activities against tumor cell lines and can be used as medicaments for treating malignant tumors.
Substituent effects on the kinetics of reductively-initiated fragmentation of nitrobenzyl carbamates designed as triggers for bioreductive prodrugs
Hay, Michael P.,Sykes, Bridget M.,Denny, William A.,O'Connor, Charmian J.
, p. 2759 - 2770 (2007/10/03)
4-Nitrobenzyl carbamates are of interest as triggers for bioreductive drugs, particularly in conjunction with the E. coli B nitroreductase, which efficiently reduces them to the corresponding hydroxylamines. These then fragment to release highly toxic amine-based toxins. While many 4-nitrobenzyl carbamate derivatives have been evaluated as bioreductive drugs, there has been no systematic study of substituent effects on the rate of this fragmentation (which should be as fast as possible following reduction). We therefore prepared a series of 2-, 3- and α-substituted 4-[N-methyl-N-(4-nitrobenzyloxycarbonyl)amino]phenylacetamides as model compounds to study these effects. The majority of the carbamates were prepared by in situ formation of the chloroformate of the appropriate 4-nitrobenzyl alcohol and reaction with methyl 4-(methylamino)phenylacetate, followed by ester hydrolysis and 1,1′-carbonyl-diimidazole (CDI) mediated coupling with N,N-dimethylaminoethylamine. The hydroxylamines were generated by 60Co γ-ray irradiation of the nitro compounds in aqueous phosphate-buffered-propan-2-ol. The reactions were analysed by reverse-phase HPLC to determine the maximum half-life (Mt1/2) of the hydroxylamines generated, and the extent of release of amine from these after 10 half-lives (t∞). The parent (unsubstituted) hydroxylaminobenzyl carbamate had a Mt1/2 of 16 min under these conditions, while that of the corresponding α-methyl analogue was 9.5 min. Electron-donating substituents on the benzyl ring also accelerated fragmentation, with the data being fitted to the equation log(Mt1/2) = 0.57σ + 1.30, where σ represents σp for 2-substituents and σm for 3-substituents. The acceleration of fragmentation of the hydroxylamines with increasing substituent electron-donation is consistent with the proposed mechanism, and is presumably due to stabilisation of the developing positive charge on the benzylic carbon. The extent of release of amine (t∞) also increased with increasing substituent electron-donation. These data suggest that the standard 4-nitrobenzyl carbamate trigger for nitroreductase enzyme (NTR) prodrugs can likely be improved on, by increasing the rate of fragmentation by the use of α-methyl and/or electron-donating benzyl substituents. The Royal Society of Chemistry 1999.
Rapamycin carbonate esters as immuno-suppressant agents
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, (2008/06/13)
Carbonate esters with rapamycin at position 42 or positions 31 and 42 have been shown to have immunosuppressant properties and are useful in the treatment of transplant rejections and autoimmune diseases. These esters are represented by the formula below: STR1 wherein: R1 and R2 are independently H or --COOR3 but both R1 and R2 cannot be H, and R3 is C1 -C6 alkyl where 1 to 3 hydrogens may be replaced by fluorine, chlorine, bromine or iodine, C3 -C8 cycloalkyl, C2 -C6 alkenyl, or Ar--(CH2)n -- where n is 0 to 6 and Ar is phenyl, phenyl substituted by fluorine, chlorine, bromine, iodine, trifluoromethyl, nitro, cyano, C1 -C6 alkyl or C1 -C6 alkoxy; pyridinyl, indolyl, quinolyl or furanyl; or a pharmaceutically acceptable salt thereof.
Process for preparing N-protected 2-aminoethanethiol
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, (2008/06/13)
Disclosed is a process for preparing N-protected 2-aminoethanethiol which proceeds via the silyl covered sulfur intermediate: STR1 wherein R1 is triorganosilyl and R2 is a readily removable N-protecting group.
