64820-07-1Relevant academic research and scientific papers
Synthesis of combretastatin A4 analogues on steroidal framework and their anti-breast cancer activity
Parihar, Swati,Kumar, Amit,Chaturvedi, Amit K.,Sachan, Naresh Kumar,Luqman, Suaib,Changkija, Bendangla,Manohar, Murli,Prakash, Om,Chanda,Khan, Feroz,Chanotiya,Shanker, Karuna,Dwivedi, Anila,Konwar, Rituraj,Negi, Arvind S.
, p. 332 - 344 (2013/11/19)
Combretastatin A4 analogues were synthesized on steroidal framework from gallic acid with a possibility of anti-breast cancer agents. Twenty two analogues were synthesized and evaluated for cytotoxicity against human breast cancer cell lines (MCF-7 & MDA-MB 231). The best analogue 22 showed potent antitubulin effect. Docking experiments also supported strong binding affinity of 22 to microtubule polymerase. In cell cycle analysis, 22 induced apoptosis in MCF-7 cells significantly. It was found to be non-toxic up to 300 mg/kg dose in Swiss albino mice in acute oral toxicity. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".
Synthesis of highly substituted hexahelicenes
Schwertel, Manfred,Hillmann, Sabine,Meier, Herbert
, p. 2020 - 2032 (2013/12/04)
C2-Symmetric hexahelicenes 3a-3g, which bear four or six alkoxy chains, were prepared in eight-to-nine reaction steps in high overall yields. The final step consisted of a twofold oxidative photocyclization of the corresponding 2,7-bis(2-phenylethenyl)naphthalenes. Long (and branched) chains provide a good solubility and processability, which is a prerequisite for applications in organic synthesis and materials science.
Oxidative cyclizations, the synthesis of aryl-substituted c-glycosides, and the role of the second electron transfer step
Smith, Jake A.,Moeller, Kevin D.
, p. 5818 - 5821 (2013/12/04)
Anodic oxidation reactions have been used to synthesize aryl- and biaryl-substituted C-glycosides. The reactions take advantage of the tendency for alcohol nucleophiles to trap nonpolar radical cations. The addition of the alcohol to the radical cation appears to be reversible, and the success of the cyclizations is dependent on the ease with which the resulting benzylic radical is oxidized.
Structure-activity relationship studies on a novel class of antiproliferative agents derived from Lavendustin A. Part I: Ring A modifications
Nussbaumer, Peter,Winiski, Anthony P.
, p. 7552 - 7560 (2008/12/23)
The potent antiproliferative agent SDZ LAP 977, which has shown efficacy in a clinical proof of concept study in actinic keratosis patients, has been previously demonstrated to block the cell cycle in mitosis. In the present study, we further explored the mode of action: SDZ LAP 977 binds to the "colchicine binding site" on tubulin and, thus, inhibits tubulin polymerization in vitro. Moreover, we established structure-activity relationships for the effect of modifications in the 2,5-dimethoxyphenyl moiety ("ring A") of the molecule on in vitro antiproliferative activity.
Effect of base on alkyltriphenylphosphonium salts in polar aprotic solvents
Ngwendson, Julius N.,Schultze, Cassandra M.,Bollinger, Jordan W.,Banerjee, Anamitro
, p. 668 - 675 (2008/09/21)
When arylmethyl phosphonium salts are treated with a base (e.g., t-BuOK or NaH) they homocouple to form symmetric 1,2-diarylethenes. In some cases, dilution and (or) use of excess base lead to very high yields of the product. This reaction is solvent sensitive: the reaction occurs only when polar aprotic solvents such as acetonitrile or DMSO are used. Other alkyl phosphonium salts (e.g., ethoxycarbonylmethyltriphenylphosphonium bromide and n- butyltriphenylphosphonium bromide) form a ylid (when an α-carbonyl group is present) or lose a phenyl group to form alkyldiphenylphosphine oxides when treated with the base. Mechanistic investigation of the homocoupling reaction indicates that the reaction proceeds through a ylid that acts as a nucleophile on an unreacted phosphonium salt. The resulting adduct undergoes elimination to form the observed product. The EIZ ratio seems to depend on the amount of the base used and the phosphonium salt involved.
Studies leading to potent, dual inhibitors of Bcl-2 and Bcl-xL
Bruncko, Milan,Oost, Thorsten K.,Belli, Barbara A.,Ding, Hong,Joseph, Mary K.,Kunzer, Aaron,Martineau, Darlene,McClellan, William J.,Mitten, Michael,Ng, Shi-Chung,Nimmer, Paul M.,Oltersdorf, Tilman,Park, Cheol-Min,Petros, Andrew M.,Shoemaker, Alexander R.,Song, Xiaohong,Wang, Xilu,Wendt, Michael D.,Zhang, Haichao,Fesik, Stephen W.,Rosenberg, Saul H.,Elmore, Steven W.
, p. 641 - 662 (2007/10/03)
Overexpression of the antiapototic proteins Bcl-2 and Bcl-xL provides a common mechanism through which cancer cells gain a survival advantage and become resistant to conventional chemotherapy. Inhibition of these prosurvival proteins is an attractive strategy for cancer therapy. We recently described the discovery of a selective Bcl-xL antagonist that potentiates the antitumor activity of chemotherapy and radiation. Here we describe the use of structure-guided design to exploit a deep hydrophobic binding pocket on the surface of these proteins to develop the first dual, subnanomolar inhibitors of Bcl-xL and Bcl-2. This study culminated in the identification of 2, which exhibited EC50 values of 8 nM and 30 nM in Bcl-2 and Bcl-xL dependent cells, respectively. Compound 2 demonstrated single agent efficacy against human follicular lymphoma cell lines that overexpress Bcl-2, and efficacy in a murine xenograft model of lymphoma when given both as a single agent and in combination with etoposide.
NOVEL DICARBOXYLIC ACID DERIVATIVES WITH PHARMACEUTICAL PROPERTIES
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Page/Page column 57, (2010/02/14)
The present invention relates to the use of compounds of the formula (I) and to their salts and stereoisomers, for the preparation of medicaments for the treatment of cardiovascular disorders.
NOVEL THYROID HORMONE RECEPTOR LIGAND, MEDICINAL COMPOSITIONS CONTAINING THE SAME AND USE THEREOF
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Page 36, (2010/02/08)
The present invention provides a compound represented by general formula (I): . or pharmaceutically acceptable salts thereof, wherein W is O, S(O)m, CH2 and the like: R1 is halogen, lower alkyl, halo-lower alkyl, CN and th
Flash vacuum pyrolysis of stabilised phosphorus ylides. Part 12. Extrusion of Ph3P from sulfonyl ylides and reactivity of the resulting sulfonyl carbenes
Aitken, R. Alan,Drysdale, Martin J.,Ferguson, George,Lough, Alan J.
, p. 875 - 880 (2007/10/03)
Twelve sulfonyl stabilised phosphorus ylides have been prepared and their behaviour upon flash vacuum pyrolysis at 600°C has been examined. Examples with an arylsulfonyl substituent undergo loss of Ph3PO to give intractable products but those with an arylmethylsulfonyl substituent separately lose Ph3P and SO2 to give products consistent with the intermediacy of sulfonyl carbenes. X-Ray structure determinations of one ylide from each series show a more significant P-O non-bonding interaction in the first case, providing some explanation for the different thermal reactivity.
Relative Reactivity and Stereoselectivity in the Wittig Reactions of Substituted Benzaldehydes with Benzylidenetriphenylphosphorane
Yamataka, Hiroshi,Nagareda, Katsushi,Ando, Katsuhiro,Hanafusa, Terukiyo
, p. 2865 - 2869 (2007/10/02)
Carbonyl carbon-14 kinetic isotope effects and substituent effects on the relative reactivity and on the cis-trans product ratio were determined in the Wittig reaction of XC6H4CHO with Ph3P=CHC6H4Y in THF at 0 deg C.The isotope effect and the Hammett ρ value were positive under both Li salt-free (12k/14k = 1.060 +/- 0.003 and ρx = 2.77 +/- 0.15) and Li salt-present (12k/14k = 1.015 +/- 0.004 and ρx = 1.38 +/- 0.12) conditions, although they were much larger in the former case.These, together with the absence of enone isomerization for the benzylidene ylide reported previously, suggested that the reactions proceed via a polar cycloaddition transition state of considerable nucleophilic character.The cis-trans ratio of the product stilbene was essentially unchanged (40:60 in the salt-free and 60:40 in the Li salt-present reaction) by the change in concentration, the mode of addition, and the molar ratio of aldehyde and ylide, and it was varied only slightly for most substituents X and Y.However, the ratio was significantly varied when o-MeO or o-Cl was introduced as X.The results could be rationalized by assuming a chelating interaction between the lone pair of the ortho substituents and the phosphorous of the ylide.
