caa a22 4500 469053607 CHVBK 20180323132837.0 cr unu---uuuuu 170328e19921001xx s 000 0 eng 10.1007/BF00130399 doi (NATIONALLICENCE)springer-10.1007/BF00130399 QSAR of conformationally flexible molecules: Comparative Molecular Field Analysis of protein-tyrosine kinase inhibitors [Elektronische Daten] [Marc Nicklaus, George Milne, Terrence Burke Jr.] Summary: Comparative Molecular Field Analysis (CoMFA) has been applied to a study of quantitative structureactivity relationships (QSAR) of conformationally flexible molecules. The relationship between three-dimensional structure and activity of 20 styrene derivatives which inhibit protein-tyrosine kinase was determined. A technique was developed that allows accurate prediction of the inhibitory activity of these molecules and identification in each case of the active conformation. The problem of multiple energetically acceptable conformations was approached in an iterative procedure. Use was made of the varying degrees of symmetry among the molecules. First, CoMFA QSAR models were developed using only those compounds that possess a symmetrical substituent pattern on the phenyl ring. These CoMFA models were then used to select the active conformers of the less symmetrical compounds in the set. Allowing multiple conformers for each compound in the dataset yielded higher crossvalidated r2 values and better predictivity of the QSAR models. Different probe atoms (C+, O−, neutral C) were explored, the O− probe atom exhibiting the highest selectivity in the conformer selection process. ESCOM Science Publishers B.V., 1992 CoMFA nationallicence Styrene derivatives nationallicence Prediction of bioactive conformation nationallicence Nicklaus Marc Laboratory of Medicinal Chemistry, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, U.S.A. aut Milne George Laboratory of Medicinal Chemistry, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, U.S.A. aut Burke Jr. Terrence Laboratory of Medicinal Chemistry, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, U.S.A. aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 6/5(1992-10-01), 487-504 0920-654X 6:5<487 1992 6 10822 https://doi.org/10.1007/BF00130399 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00130399 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nicklaus Marc Laboratory of Medicinal Chemistry, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, U.S.A aut NATIONALLICENCE 700 1- Milne George Laboratory of Medicinal Chemistry, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, U.S.A aut NATIONALLICENCE 700 1- Burke Jr Terrence Laboratory of Medicinal Chemistry, Developmental Therapeutics Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, 20892, Bethesda, MD, U.S.A aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 6/5(1992-10-01), 487-504 0920-654X 6:5<487 1992 6 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer