Abstract
A practical synthesis of 2,3-diarylated 2H-benzo[e][1,2]thiazine 1,1-dioxides and their 3,4-dihydro derivatives was developed. ortho-Methyl lithiation of N-aryl-o-toluenesulfonamide followed by reaction with aryl aldehydes gave carbinol sulfonamides, which were either converted directly, or first oxidized to their ketones and converted, to 2,3-diarylated six-membered benzosultams via a TMSCl-NaI-MeCN mediated cyclization. A library of benzosultams was synthesized and evaluated for inhibitory activity against MCF-7 cells. Compound 3 in the 3,4-dihydro (saturated) series and compound 8 in the unsaturated series exhibited the highest potencies with growth inhibition (GI50) values of 0.8 and 18.0 μM, respectively. Molecular modeling studies suggest that these compounds can associate with the colchicine binding site on microtubules. However, experimental assessments of that and other mechanistic possibilities are still ongoing.
Keywords: TMSCl-NaI-MeCN, cyclization, benzo[e][1,2]thiazines, benzosultams, MCF-7 cells, anticancer, synthesis of 2,3-diarylated, 2H-benzo[e][1,2]thiazine, microtubules, 3,4-dihydro (saturated)
Medicinal Chemistry
Title: Syntheses of 2,3-Diarylated 2H-Benzo[e][1,2]Thiazine 1,1-Dioxides and their 3,4-Dihydro Derivatives, and Assessment of their Inhibitory Activity Against MCF-7 Breast Cancer Cells
Volume: 7 Issue: 6
Author(s): Yuan-Yuan Shan, Cheng-Mei Zhang, Long-Qiang Tang, Zhao-Peng Liu, Nicole R. Bearss, Jeffrey G. Sarver, Amarjit Luniwal and Paul W. Erhardt
Affiliation:
Keywords: TMSCl-NaI-MeCN, cyclization, benzo[e][1,2]thiazines, benzosultams, MCF-7 cells, anticancer, synthesis of 2,3-diarylated, 2H-benzo[e][1,2]thiazine, microtubules, 3,4-dihydro (saturated)
Abstract: A practical synthesis of 2,3-diarylated 2H-benzo[e][1,2]thiazine 1,1-dioxides and their 3,4-dihydro derivatives was developed. ortho-Methyl lithiation of N-aryl-o-toluenesulfonamide followed by reaction with aryl aldehydes gave carbinol sulfonamides, which were either converted directly, or first oxidized to their ketones and converted, to 2,3-diarylated six-membered benzosultams via a TMSCl-NaI-MeCN mediated cyclization. A library of benzosultams was synthesized and evaluated for inhibitory activity against MCF-7 cells. Compound 3 in the 3,4-dihydro (saturated) series and compound 8 in the unsaturated series exhibited the highest potencies with growth inhibition (GI50) values of 0.8 and 18.0 μM, respectively. Molecular modeling studies suggest that these compounds can associate with the colchicine binding site on microtubules. However, experimental assessments of that and other mechanistic possibilities are still ongoing.
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Shan Yuan-Yuan, Zhang Cheng-Mei, Tang Long-Qiang, Liu Zhao-Peng, R. Bearss Nicole, G. Sarver Jeffrey, Luniwal Amarjit and W. Erhardt Paul, Syntheses of 2,3-Diarylated 2H-Benzo[e][1,2]Thiazine 1,1-Dioxides and their 3,4-Dihydro Derivatives, and Assessment of their Inhibitory Activity Against MCF-7 Breast Cancer Cells, Medicinal Chemistry 2011; 7 (6) . https://dx.doi.org/10.2174/157340611797928307
DOI https://dx.doi.org/10.2174/157340611797928307 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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