Principal Components Describing Biological Activities and Molecular Diversity of Heterocyclic Aromatic Ring Fragments
- 1 January 1996
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 39 (20) , 4065-4072
- https://doi.org/10.1021/jm960058h
Abstract
Ten physicochemical variables have been calculated for each of 100 different aromatic rings. These variables were selected because of their potential involvement in the molecular recognition of drug−receptor binding interactions, and they include size, lipophilicity, dipole magnitude and orientation, HOMO and LUMO energies, and electronic point charges. A total of 59 different aromatic ring systems were studied including monocyclics and [5.5]-, [6.5]- and [6.6]-fused bicyclics. A principal components analysis of these results generated four principal components which account for 84% of the total variance in the data. These principal components provide a quantitative measure of molecular diversity, and their relevance for structure−activity relationships is discussed. The principal components correlate with the in vitro biological activity of heterocyclic aromatic fragments within a series of previously reported HIV-1 reverse transcriptase inhibitors (Saari, W. S.; et al. J. Med. Chem. 1992, 35, 3792−3802).Keywords
This publication has 14 references indexed in Scilit:
- A New Set of Principal Properties for Heteroaromatics Obtained by GRIDQuantitative Structure-Activity Relationships, 1996
- Molecular Similarity Determination of Heteroaromatics Using CoMFA and Multivariate Data AnalysisQuantitative Structure-Activity Relationships, 1994
- “Classical†and “Magnetic†Aromaticities as new Descriptors for Heteroaromatics in QSAR. Part 3 [1]. Principal Properties for HeteroaromaticsQuantitative Structure-Activity Relationships, 1993
- Structure-activity relationships of antifilarial antimycin analogs: a multivariate pattern recognition studyJournal of Medicinal Chemistry, 1990
- Principal Properties for Aromatic Substituents. A Multivariate Approach for Design in QSARQuantitative Structure-Activity Relationships, 1989
- On the significance of clusters in the graphical display of structure-activity dataJournal of Medicinal Chemistry, 1986
- A computational procedure for determining energetically favorable binding sites on biologically important macromoleculesJournal of Medicinal Chemistry, 1985
- Quantitative structure-activity relationships employing independent quantum chemical indexesJournal of Medicinal Chemistry, 1983
- Conformational study of a methylating agent: the crystal structure of S-methyl-L-methionine chloride.HCl (vitamin U hydrochloride)Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials, 1977
- Field and resonance components of substituent effectsJournal of the American Chemical Society, 1968