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Ali, Hamed I. Department of Drug Discovery and Development, Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Ashida, Noriyuki Biology Laboratory, Research and Development Division, Yamasa Shoyu Co.
Nagamatsu, Tomohisa aDepartment of Drug Discovery and Development, Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Various novel 10-alkyl-2-deoxo-2-methylthio-5-deazaflavins have been synthesized by reaction of 6-(N-alkylanilino)-2-methylthiopyrimidin-4(3H)-ones with Vilsmeier reagent. The similar 2-(N-substituted amino) derivatives were prepared by nucleophilic replacement reaction of the 2-methylthio moiety by appropriate amines. The 2-oxo derivatives (i.e., 5-deazaflavins) were obtained by acidic hydrolysis of the 2-methylthio derivatives. The antitumor activities against CCRF-HSB-2 and KB cells and the antiviral activities against HSV-1 and HSV-2 have been investigated in vitro, and many compounds showed promising antitumor activities. Furthermore, AutoDock molecular docking into PTK has been done for lead optimization of these compounds as potential PTK inhibitors. Whereas, the designed 2-deoxo-5-deazaflavins connected with amino acids at the 2-position exhibited the good binding affinities into PTK with more hydrogen bonds.
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This is a author's copy,as published in Bioorganic & Medicinal Chemistry , 2007 Vol.15 Issue.19 pp.6336-6352
Publisher URL: http://dx.doi.org/10.1016/j.bmc.2007.06.058
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Copyright © 2008 by Elsevier Ltd.
Bioorganic & Medicinal Chemistry
Pergamon-Elsevier Science Ltd.
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