St Andrews Research Repository

St Andrews University Home
View Item 
  •   St Andrews Research Repository
  • Biology (School of)
  • Biology
  • Biology Theses
  • View Item
  •   St Andrews Research Repository
  • Biology (School of)
  • Biology
  • Biology Theses
  • View Item
  •   St Andrews Research Repository
  • Biology (School of)
  • Biology
  • Biology Theses
  • View Item
  • Login
JavaScript is disabled for your browser. Some features of this site may not work without it.

Studies on N-hydroxyguanidine derivatives, potential nitric oxide donor drugs

Thumbnail
View/Open
NeilAndersonPhDThesis.pdf (39.98Mb)
Date
1999
Author
Anderson, Neil D.
Supervisor
Botting, Nigel
Funder
Biotechnology and Biological Sciences Research Council (Great Britain)
Metadata
Show full item record
Altmetrics Handle Statistics
Abstract
The ability of substituted N-hydroxyguanidines to act as nitric oxide donor drugs has been previously established. To further investigate the potential of this class of compound as nitric donor drugs a number of new N-hydroxyguanidines were prepared. The compounds were synthesised and then subjected to a number of chemical and biological tests. A number of the examples prepared were indeed shown to be oxidised under chemical conditions to give nitric oxide. The nitric oxide was tested for using the Greiss test. One example, 1-benzyl-1-methyl-2-hydroxyguanidine showed biological activity and was found to be a vasodilator. In addition an X-ray crystal structure of this compound was obtained which gave a further insight into the conformation of this type compound and related analogues. A number of ureas were also prepared for use in the biological and chemical testing. Under chemical conditions the ureas were not oxidised thus indicating that the hydroxyguanidine functionality was required for nitric oxide generation. O-Substituted N-hydroxyguanidines were also prepared in an effort to examine the possibility of selectively targeting the molecule to the site of action for nitric oxide release. These compounds were found to produce a small amount of nitric oxide under chemical oxidation, therefore confirming their potential as potential nitric oxide donor compounds. Acid catalysed decomposition of O-THP-1,1,-dibenzyl-2- hydroxyguanidine was studied. The reaction was carried out at various pHs and was monitored using HPLC. It was found that the THP protecting group could be removed to give the free N-hydroxyguanidine. More easily removed O-substituents are probably required to produce successful prodrugs. However the reaction only gave a reasonable rate at a very low pH (t1/2 = 122 s at pH 0). A number of O-substituted hydroxylamines were then prepared in an attempt to increase the range of O-substituted N-hydroxyguanidines that could be obtained.
Type
Thesis, PhD Doctor of Philosophy
Collections
  • Biology Theses
URI
http://hdl.handle.net/10023/14108

Items in the St Andrews Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.

Advanced Search

Browse

All of RepositoryCommunities & CollectionsBy Issue DateNamesTitlesSubjectsClassificationTypeFunderThis CollectionBy Issue DateNamesTitlesSubjectsClassificationTypeFunder

My Account

Login

Open Access

To find out how you can benefit from open access to research, see our library web pages and Open Access blog. For open access help contact: openaccess@st-andrews.ac.uk.

Accessibility

Read our Accessibility statement.

How to submit research papers

The full text of research papers can be submitted to the repository via Pure, the University's research information system. For help see our guide: How to deposit in Pure.

Electronic thesis deposit

Help with deposit.

Repository help

For repository help contact: Digital-Repository@st-andrews.ac.uk.

Give Feedback

Cookie policy

This site may use cookies. Please see Terms and Conditions.

Usage statistics

COUNTER-compliant statistics on downloads from the repository are available from the IRUS-UK Service. Contact us for information.

© University of St Andrews Library

University of St Andrews is a charity registered in Scotland, No SC013532.

  • Facebook
  • Twitter