96014-61-8Relevant academic research and scientific papers
4-(3-Halo/amino-4,5-dimethoxyphenyl)-5-aryloxazoles and-N-methylimidazoles That Are cytotoxic against combretastatin a resistant tumor cells and vascular disrupting in a cisplatin resistant germ cell tumor model
Schobert, Rainer,Biersack, Bernhard,Dietrich, Andrea,Effenberger, Katharina,Knauer, Sebastian,Mueller, Thomas
experimental part, p. 6595 - 6602 (2010/11/19)
New combretastatin A analogues featuring oxazole or N-methylimidazole bridged Z-alkenes and halo-or amino-substituted A-rings were tested against various cancer cell lines and in testicular germ cell tumor xenografts in mice. Imidazoles with 3-halo-4,5-dimethoxy substituted A-rings and 3-amino-4-methoxy substituted B-rings (7b and 8b) were efficacious at nanomolar concentrations against cells of combretastatin A refractory HT-29 colon carcinoma, multidrug-resistant MCF-7/Topo breast carcinoma, and cisplatin-resistant 1411HP testicular germ cell tumor. They induced apoptosis and inhibited tubulin polymerization. While well tolerated by mice at high doses, these imidazoles initiated extensive intratumoral hemorrhage and regressions of highly vascularized 1411HP xenografts.
Potent, orally active heterocycle-based combretastatin A-4 analogues: Synthesis, structure - Activity relationship, pharmacokinetics, and in vivo antitumor activity evaluation
Wang, Le,Woods, Keith W.,Li, Qun,Barr, Kenneth J.,McCroskey, Richard W.,Hannick, Steven M.,Gherke, Laura,Credo, R. Bruce,Hui, Yu-Hua,Marsh, Kennan,Warner, Robert,Lee, Jang Y.,Zielinski-Mozng, Nicolette,Frost, David,Rosenberg, Saul H.,Sham, Hing L.
, p. 1697 - 1711 (2007/10/03)
The synthesis and structure - activity relationship study of a series of compounds with heterocycles in place of the cis double bond in combretastatin A-4 (CA-4) are described. Substituted tosylmethyl isocyanides were found to be the key intermediates in construction of the heterocycles. Cytotoxicities of the heterocycle-based CA-4 analogues were evaluated against NCI-H460 and HCT-15 cancer cell lines. 3-Amino-4-methoxyphenyl and N-methyl-indol-5-yl were the best replacements for the 3-hydroxy-4-methoxyphenyl in CA-4. 4,5-Disubstituted imidazole was found to be the best for the replacement of the cis double bond in CA-4. Medicinal chemistry efforts led to the discovery of compounds 24h and 25f that were found to be 32 and 82% bioavailable, respectively, in rat. Evaluation of 24h and 25f against murine M5076 reticulum sarcoma in mice revealed that both compounds were orally efficacious with an increase in life span of 38.5 and 40.5%, respectively.
ACTIVATING EFFECT OF THE IMINIUM GROUP IN AROMATIC NUCLEOPHILIC SUBSTITUTION OF AN ALKOXY GROUP AND HALOGEN ATOMS BY THE ACTION OF NITROGEN BASES
Blokhin, A.V.,Bundel, Yu. G.,Terenin, V.I.,Kurtz, A.L.
, p. 2116 - 2123 (2007/10/02)
The characteristics of aromatic nucleophilic substitution with activation by the iminium group in the iminium derivatives of p-alkoxy- and p-halogenobenzaldehydes were investigated.They are determined by the concurrent addition of the nucleophilic agents at the C=N multiple bond.The activating effect of the iminium group depends on the nature of the leaving group, the solvent, the substituent in the benzene ring, and the nature and concentration of the protonating agent.The action of heat on p-methoxybenzylidenemethylamine with a tenfold excess of methylamine hydrochloride in a 30percent alcohol solution of methylamine at 150 deg C for 40 h leads to substitutioon of the methoxymethylamino group with a yield of 90percent.
