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Optimization of Important Early ADME(T) Parameters of NADPH Oxidase-4 Inhibitor Molecules
- Source :
- Medicinal Chemistry; March 2012, Vol. 8 Issue: 2 p174-181, 8p
- Publication Year :
- 2012
-
Abstract
- Through their reactive oxygen species (ROS) producing function, NADPH oxidase (NOX) enzymes have been linked to several oxidative stress related diseases. In our recently published paper [1] we have already shown the NOX4 inhibitory effect of diverse, molecule sub-libraries and their biological importance. We also presented our work connected to potential anti-tumour molecules and the relationship between their biological activity and physico-chemical properties [2]. As an extension of these studies further physico-chemical and biological investigation has been carried out on a molecule group included NOX4 inhibitory chromanone compounds. Here we describe the optimization of early ADME(T) parameters determining lipophilicity, phospholipophilicity and permeability linked to structure-activity relationship. We prove that optimal lipo- and phospholipophilicty can be also determined in case of NOX4 inhibitors and a comparison will be made between the chemically similar isochromanone and chromanone molecular libraries. It will be also shown how to predict the effect of different substituents on permeability, lipo- and phospholipophilicity and also the biological differences between anti-tumour molecules and NOX4 inhibitors according to their penetration ability.
Details
- Language :
- English
- ISSN :
- 15734064
- Volume :
- 8
- Issue :
- 2
- Database :
- Supplemental Index
- Journal :
- Medicinal Chemistry
- Publication Type :
- Periodical
- Accession number :
- ejs27412296