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| Titel: |
The Design of Therapeutic Chelating Agents |
| Auteur: |
Jones, Mark M. |
| Verschenen in: |
Journal of coordination chemistry |
| Paginering: | Jaargang 23 (1991) nr. 1-4 pagina's 187-200 |
| Jaar: |
1991-06-01 |
| Inhoud: |
The factors involved in the design of therapeutic chelating agents are outlined on the basis of the theoretical analyses of ligand design and experimental data obtained in animal studies. The starting point in such design must always be those factors which assure that a sufficiently high stability constant be achieved, and here the analyses presented by Martell and his co-workers furnish a general approach. If the removal of intracellular metal deposits is to be achieved, additional factors need to be considered to incorporate variables which govern the interaction of the chelating agent with the membrane systems of those organs within which the toxic metal is concentrated. For these, the QSAR (quantitative structure activity relationship) procedure of Hansch furnishes a useful guide. This allows the development of direct structure-efficacy correlations (DSEC) involving molecular parameters in addition to those which are directly involved in the determination of the stability constant. In several cases data are available which indicate how the relative efficacy of two chelating agents with essentially identical stability constant expectations is dependent upon structural features which govern the relative ease with which such molecules can gain access to intracellular deposits. The combination of these approaches allows the joint use of in vitro and in vivo data to design improved therapeutic chelating agents with an increased probability of success when tested in vivo. |
| Uitgever: |
Taylor & Francis |
| Bronbestand: |
Elektronische Wetenschappelijke Tijdschriften |
Details van artikel 65 van 73 gevonden artikelen
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