China Science

The purpose of this research was to analyze the pharmacological properties of a homologous series of nitrogen mustard (N-mustard) agents formed after inserting 1 to 9 methylene groups (-CH2-) between 2-N(CH2CH2Cl)2 groups. These compounds were shown to have significant correlations; associations in their properties after analysis by pattern recognition methods including hierarchical classification, cluster analysis, nonmetric multi-dimensional scaling (MDS), detrended correspondence analysis, K-means cluster analysis, discriminant analysis,; self-organizing tree algorithm (SOTA) analysis. Detrended correspondence analysis showed a linear-like association of the 9 homologs,; hierarchical classification showed that each homolog had great similarity to at least one other member of the series—as did cluster analysis using paired-group distance measure. Nonmetric multi-dimensional scaling was able to discriminate homologs 2; 3 (by number of methylene groups) from homologs 4, 5,; 6 as a group,; from homologs 7, 8,; 9 as a group. Discriminant analysis, K-means cluster analysis,; hierarchical classification distinguished the high molecular weight homologs from low molecular weight homologs. As the number of methylene groups increased the aqueous solubility decreased, dermal permeation coefficient increased, Log P increased, molar volume increased, parachor increased,; index of refraction decreased. Application of pattern recognition methods discerned useful interrelationships within the homologous series that will determine specific; beneficial clinical applications for each homolog; methods of administration.

Ronald Bartzatt1Email:bartzatt@mail.unomaha.edu?Laura Donigan1
[1] Department of Chemistry, Laboratory of Pharmaceutical Studies, University of Nebraska, Durham Science Center, 6001 Dodge St, 68182 Omaha, NE