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1408353477Abstract-Book-Euroqsar- B.Gjorgjeska.Pdf Abstract-Book-EuroQSAR.indd 1 18/08/2014 11:07:44 Table of Content Plenary Lectures and Hansch Session Abstracts-------------------------------------------------------------------------3 Oral Communications Abstracts--------------------------------------------------------------------------------------------40 Posters Abstracts----------------------------------------------------------------------------------------------------------------74 List of Abstracts --------------------------------------------------------------------------------------------------------------- 232 List of Authors ----------------------------------------------------------------------------------------------------------------- 243 - 2 - Plenary Lectures and Hansch Session Abstracts - 3 - Toshio Fujita Kyoto University, Japan Education: 1948~1951: Kyoto University, Department of Agricultural Chemistry 1961~1963: Pomona College, Department of Chemistry, Postdoctoral Fellow (Professor Corwin Hansch) 1963~1964: University of Illinois, Department of Chemistry, Postdoctoral Fellow (Professor Kenneth Rinehart) Degrees: B.S. Kyoto University, March 1951 D.Sc. Kyoto University, February 1962 Professional Positions: 1951 ~ 1964: Instructor, Kyoto University 1964 ~ 1966: Lecturer, Kyoto University 1966 ~ 1981: Associate Professor, Kyoto University 1981 ~ March 1992: Professor, Kyoto University 1992 ~ 1998: Consultant, Fujitsu Kansai Systems Laboratory March 1992 to date: Professor Emeritus, Kyoto University Professional Society Memberships: Japan Society for Bioscience, Biotechnology and Agrochemistry (Formerly Agricultural Chemical Society of Japan). Chemical Society of Japan. Pharmaceutical Society of Japan. Pesticide Science Society of Japan. American Chemica1 Society. Editorial and Advisory Positions: Quantitative Structure-Activity Relationship (Wiley-VCH): 1982 ~ 2003 QSAR and Combinatorial Sciences (Wiley-VCH): 2004 to date Pesticide Biochemistry and Physiology (Academic Press): 1987 ~ 1997 Pest Management Science (Formerly Pesticide Science): 1990 to date Pharmacochemistry Library (Elsevier): 1989 ~ 2002 Professional Activities: Organizing Committee and Scientific Program Committee Member of the 5th International Congress of Pesticide Chemistry, Kyoto, 1982 Vice President, The Pesticide Science Society of Japan, 1983~1984 President, The Pesticide Science Society of Japan, 1985~1986 Chairman, The Kansai Section of the Japan Society for Bioscience, Biotechnology and Agrochemistry, 1989~1990 - 4 - PL01 (Q)SAR: THE LIFELONG LEARNING FOR MY RESEARCH CAREER Toshio Fujita Professor Emeritus at Kyoto University Bioreguration and Pesticide Chemistry #38-1 Iwakura-Miyakecho, Sakyoku (Home), 606- 0022 Kyoto, Japan As is well-known, the classical QSAR was first discovered by Professor Corwin Hansch and his group at Pomona College, Claremont, California, almost half a century ago. It was just after I joined him as a postdoctoral fellow in 1961. I was very fortunate to participate directly in this discovery. Both of us had been studying independently the structure-activity relationship of plant growth regulators of the substituted aromatic carboxylic acid type. At Pomona, variations in the growth promotion of a set of substituted phenoxyacetic acids to oat sprouts were examined in terms of the effects of substituents introduced into the unsubstituted reference. We had recognized that more than single physicochemical effect “simultaneously” participates in variations in the plant growth activity, and the first QSAR equation was formulated in the framework of so-called “linear free-energy relationships” using multiple regression analyses and such electronic parameters as the Hammett σ and a hydrophobic parameter as the π value. The latter was defined at that time from the 1-octanol/water partition coefficients. This first equation was subject to a couple of revisions because of renewed hypotheses for the electronic mechanism of substituents and a later inclusion of the bilinear model for size effect of substituents represented by STERIMOL steric parameters. Even though these correlations could be thought “original as well as fundamental”, they were only obtained under considerably restricted conditions. For instance, most compounds substituted at the ortho positions, most 3,5-disubstituted derivatives, 4-substituted analogs with substituents larger than Br as well as compounds with such hydrogen bondable/ionizable groups as OH and COOH were omitted from the analyses. After returning to Kyoto, I expanded and deepened the QSAR research mostly in major insecticidal sets of compounds in the Department of Agricultural Chemistry. The compound sets include acetylcholinesterase inhibitors, BHC and DDT types of compounds, synthetic pyrethroide analogs, and substituted benzoylphenylureas and dibenzoylhydrazines. In these research projects, we usually synthesized compounds and measured their biological activity by ourselves. These QSAR studies also came off well when compound sets are devoid of restrictive conditions as in the case of phenoxyacetic acids indicated above. Thus, we emphasized our effort also on exploring procedures to overcome restrictions and/or proving their free-energy related background. We found a procedure to analyze the “ortho-effect” by hypothesizing that their electronic and steric effects could be composed of ordinary and proximity components so that ortho-substituted compounds can be included on the same basis as meta- and para-substituted compounds in the QSAR analyses. We also suggested free-energy related background of STERIMOL steric parameters defined mechanistically from width and length of substituents in the unit of Å. In this lecture, I would like to show mainly examples of our physical-organic chemical studies performed to improve mechanistic understanding of the classical QSAR results in general. As a chemist starting his career from syntheses of small-molecular bioactive compounds, statistical as well as physical-organic chemical disciplines to explore QSAR were rather foreign and perseverant, but they have been continuingly fruitful and enjoyable learnings through my life of 85 years old. - 5 - Peter Ertl Novartis Institute for Biomedical Research, Switzerland eter Ertl studied organic chemistry and received his PhD at the University of Bratislava before joining Ciba-Geigy in Basel. After a merger with Sandoz to form Novartis he became Head of Pthe Cheminformatics group in Pharma Research, responsible for development of new methods for the calculation of molecular properties and cheminformatics tools. Peter is author of more than 100 publications and book chapters concerning all areas of cheminformatics and computational chemistry. In the cheminformatics community he is best known as author of the JME structure drawing applet and the fast fragment based method to calculate molecular polar surface area. http://peter-ertl.com - 6 - PL02 NAVIGATION IN CHEMICAL SPACE TOWARDS BIOLOGICAL ACTIVITY Peter Ertl Novartis Institutes of BioMedical Research, Basel, Switzerland www.peter-ertl.com One of the most common tasks that cheminformatics experts in pharmaceutical industry are facing practically daily is analysis and visualization of large collections of molecules. Typical areas, where this is needed are analysis and enhancement of company compound archive, analysis of high-throughput screening data, design of combinatorial libraries, chemogenomics analyses and many others. But also researchers in academia are facing similar challenges when analyzing large public molecular databases that become available recently or even structures generated in silico. This presentation will provide overview of various methods used to analyze and visualize chemical space with particular focus on needs of medicinal chemists. When displaying results, for chemists it is of great importance that the molecules are represented by their actual structures, or at least by their scaffolds and not only by points as it is common in other scientific fields. This particular requirement makes chemistry visualizations challenging because of necessity to squeeze a lot of information on rather limited computer screen real estate. In the presentation various chemistry visualization techniques will be discussed, starting from classical display of molecules as tables and grids, through visualization based on analysis of scaffold, up to advanced cheminformatics visualizations techniques recently developed at Novartis, such as a method for natural ordering or scaffolds or Molecule Cloud diagrams. References 1) Intuitive Ordering of Scaffolds and Scaffold Similarity Searching Using Scaffold Keys. P. Ertl, J. Chem. Inf. Model. 54, 1617 (2014) 2) The Molecule Cloud - compact visualization of large collections of molecules, P. Ertl and B. Rohde, J. Cheminf. 4:12 (2012) 3) The Scaffold Tree - Visualization of the scaffold universe by hierarchical scaffold classification. A. Schuffenhauer, P. Ertl, S. Roggo, S. Wetzel, M. Koch, H. Waldmann, J. Chem. Inf. Modelling. 47, 47-58 (2007). 4) Quest for the Rings - In silico exploration of ring universe to identify novel bioactive heteroaromatic scaffolds. P. Ertl, S. Jelfs, J. Muehlbacher, A. Schuffenhauer, P. Selzer, J. Med. Chem. 49, 4568-4573 (2006). - 7 - John C. Reed F. Hofmann-La-Roche, Switzerland ohn C Reed is Global Head of Roche Pharma Research and Early Development (pRED), and Member of the Enlarged Roche Corporate Executive Committee. With his broad scientific and Jmedical background, Dr Reed is responsible for driving pRED’s strategy of
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