Year
2014
Degree Name
Doctor of Philosophy
Department
School of Chemistry
Recommended Citation
Rashad Ahmed, Adel Ahmed, The medicinal chemistry development for new antimicrobial chemotherapeutics, Doctor of Philosophy thesis, School of Chemistry, University of Wollongong, 2014. https://ro.uow.edu.au/theses/4132
Abstract
Chapter 2 discusses the synthesis of the arenearylpyrimidylmethanes (AAPMs) series was investigated to further develop the structure activity relationships (SAR) of these compounds as potential anti-chikungunya virus agents. 1-(4,6-Dichloropyrimidin-5-yl)- 2-methyl-1-(3-nitrophenyl)propan-1-ol was prepared in 50% yield. Subsequent dehydration and amination gave the intermediate 4-amino-6-chloro-5-(2-methyl-1-(3- nitrophenyl)prop-1-en-1-yl)pyrimidine in 90% yield, over two steps. Final amination using either 1-amino-3-(diethylamino)propan-2-ol or N1,N1-diethylpentane-1,4-diamine was attempted using several conditions, however, the desired final AAPM derivatives were not obtained.
Further modification of the synthetic protocol was achieved through the replacement of the 4,6-dichloropyrimidine with the less hindered 4-chloropyridine. The 4- chloropyridin-3-yl alcohols were prepared in 42-52% yield. Subsequent dehydration afforded the 4-chloropyridine alkenes in 62-85% yield. Final replacement of the chlorine atom with the amine N1,N1-diethylpentane-1,4-diamine was attempted under different conditions, however, the desired products were not obtained. Instead the 3- (cyclobutylidene(4-phenoxypyridin-3-yl)methyl)aniline was isolated when using phenol as a solvent for the amination reaction. Replacement of the N1,N1-diethylpentane-1,4- diamine with the secondary amine morpholine gave 4-(3-(cyclopropylidene(3- nitrophenyl)methyl)pyridin-4-yl)morpholine in 65% yield.
FoR codes (2008)
030401 Biologically Active Molecules, 030402 Biomolecular Modelling and Design, 030403 Characterisation of Biological Macromolecules
Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.