Karaaslan Cigdem
Ankara University Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Ankara, Turkey.
Turk J Pharm Sci. 2020 Feb;17(1):108-114. doi: 10.4274/tjps.galenos.2019.44270. Epub 2020 Feb 19.
In our previous studies we synthesized some potent antiparasitic, anticancer and antimicrobial amidine derivatives. Despite all their potent activities, it is well known that due to their cationic charge, amidine derivatives pose a serious problem in terms of bioavailability. The main purpose of this study is to prepare amidoxime derivatives of previously synthesized potent amidine derivatives as prodrugs in order to increase their bioavailabilities.
The targeted benzimidazole amidoximes were synthesized from their nitrile derivatives. The nitrile groups of these benzimidazole carbonitriles were converted to N-hydroxy benzamidine derivatives (amidoxime derivatives, 20-29) in the presence of NHOH.HCI and KO-t-Bu in dimethyl sulfoxide. Structures of newly synthesized amidoxime derivatives were elucidated with 1H-NMR, 13C-NMR and some 2D NMR techniques like COSY, NOESY, HSQC and HMBC.
A new series of benzimidazole amidoximes were synthesized and their structural elucidations were done in this study.
In order to solve the potential bioavailability problem of potent amidine derivatives, we prepared the prodrugs of those potent amidine derivatives as their amidoxime derivatives. studies of both previous amidine derivatives and amidoxime prodrugs of those amidines which were synthesized in this study are planned to perform in our ongoing studies.
在我们之前的研究中，我们合成了一些强效的抗寄生虫、抗癌和抗菌脒衍生物。尽管它们具有所有这些强效活性，但众所周知，由于其阳离子电荷，脒衍生物在生物利用度方面存在严重问题。本研究的主要目的是制备先前合成的强效脒衍生物的偕胺肟衍生物作为前药，以提高它们的生物利用度。
目标苯并咪唑偕胺肟由其腈衍生物合成。在二甲亚砜中，这些苯并咪唑腈的腈基在盐酸羟胺和叔丁醇钾存在下转化为N-羟基苯甲脒衍生物（偕胺肟衍生物，20 - 29）。通过1H-NMR、13C-NMR以及一些二维NMR技术如COSY、NOESY、HSQC和HMBC对新合成的偕胺肟衍生物的结构进行了阐明。
本研究合成了一系列新苯并咪唑偕胺肟并对其结构进行了阐明。
为了解决强效脒衍生物潜在的生物利用度问题，我们制备了那些强效脒衍生物的前药，即它们的偕胺肟衍生物。计划在我们正在进行的研究中对先前的脒衍生物以及本研究中合成的那些脒的偕胺肟前药进行研究。
