Medchem 2017 Abstract Book.Pdf

3rd Russian Conference on Medicinal Chemistry Kazan, September 28 – October 03, 2017 Abstract Book 1 Copyright © Organizing Committee of 3rd Russian Conference on Medicinal Chemistry, 2017. All rights reserved 3rd Russian Conference on Medicinal Chemistry. Abstract book. – Kazan Federal University, 2017, 280 p. The book contains abstracts of all the scientific sessions of the 3rd Russian Conference on Medicinal Chemistry (Kazan, September 28 – October 03, 2017), including plenary lectures, keynote presentations, oral and poster presentations, round-table talks, and correspondent presentations. It also includes the information from industrial partners of the conference, and the author index. 2 The 3rd Russian Conference on Medicinal Chemistry is held under the auspices of the European Federation for Medicinal Chemistry. The Conference Organizers Kazan (Volga region) Federal University Government of the Republic of Tatarstan Russian Academy of Sciences Federal Agency for Scientific Organizations Ministry of Education and Science of the Russian Federation Kazan Scientific Center of the Russian Academy of Sciences Tatarstan Academy of Sciences Institute of organic and physical chemistry, RAS, Kazan Institute of physiologically active compounds, RAS, Chernogolovka Mendeleev Chemical Society of the Republic of Tatarstan M.V. Lomonosov Moscow State University, the Chemical Faculty The General Partner: KHIMEXPERT LLC The partners: Tatkhimpharmpreparaty JSC (Platinum Sponsor) ChemRar (General Sponsor of the Young Scientists’ Symposium) Nanopharma Development LLC (Gold Sponsor) Millab (Silver Sponsor) Dia-M (Silver Sponsor) BIOCAD (Silver Sponsor) Merck (Silver Sponsor) TatKhimProduct (Bronze Sponsor) Laboratory Equipment and Instruments JSC (Bronze Sponsor) Acrus (Bronze Sponsor) 3 The 3rd Russian Conference on Medicinal Chemistry is dedicated to the memory of Academician Nikolay Serafimovich Zefirov (1935-2017) 4 CONTENT Plenary Lectures 7 Young scientists' symposium «Innovative developments of 13 young scientists in the field of drug design» Special session dedicated to the memory of Acad. Nikolay 33 Zefirov Scientific session «Target-directed design of novel drugs» 39 Scientific session «Novel synthetic and technological approaches 49 in medicinal chemistry» Scientific session «Scientific and methodological aspects of 57 development of novel drugs» Scientific session «Bioinorganic medicinal chemistry» 67 Scientific session «Natural-product-based drug design» 79 Scientific session «Computational drug design» 89 Poster session №1 99 Poster session №2 137 Poster session №3 177 Correspondent presentations 213 Round table materials 263 Information from the Industrial Partners 267 Author Index 275 Information from the Publishing Partners 279 5 6 PLENARY LECTURES 7 Advanced Anti-infective Agents Against Emerging Diseases Reuben Jih-Ru Hwu1,2, S.-C. Tsay1, N. K. Gupta1, W.-C. Huang1, J. Neyts3, M. Bolognesi4, and M. J. van Hemert5 1Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan 2Department of Chemistry, National Central University, Jhongli City, 32001, Taiwan 3Rega Institute for Medical Research, KatholiekeUniversiteit, Leuven, B-3000, Belgium 4Department of BioSciences, University of Milano, Milano, Italy 5Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands Email: [email protected] Our laboratory has successfully established 12 compound libraries after five years of research on the SILVER project of the 7th Framework Program funded by European Commission. More than 800 new conjugated compounds containing nucleoside, heterocycle, coumarin, and sulfonate moieties were designed and synthesized, of which the antiviral activities were explored by our SILVER Consortium partners. Results from Leuven University (Belgium), University of Milano (Italy), and Leiden University Medical Center(Leiden) indicate that more than 15 compounds possessed significant potency and identified as leads against chikungunya virus and norovirus. It is the aim of the SILVER project to develop new drugs for emerging and the relatively neglected diseases caused by RNA viruses. Surmarin, its derivatives, bis(benzofuran–thiazolidinone)s, and bis(benzofuran– thiazinanone)s have also been designed and synthesized. These compounds constitute new types of drug leads for anti-chikungunya virus and norovirus [1-3]. References [1] I. C. Albulescu, M. V. Hoolwerff, L. A. Wolters, E. Bottaro, C. Nastruzzi, S. C. Yang, S.-C. Tsay, J. R. Hwu, E. J. Snijder, and M. J. van Hemert, Antiviral Res.2015, 121, 3946. [2] J. R. Hwu, M. Kapoor, S.-C. Tsay, C.-C. Lin, K. C. Hwang, J.-C. Horng, I.-C. Chen, F.-K. Shieh, P. Leyssen, and J. Neyts, Antiviral Res.2015, 118, 103–109. [3] R. Croci1, M. Pezzullom, D. Tarantino, M. Milani, S.-C. Tsay, R. Sureshbabu, Y.-J. Tsai, E. Mastrangelo, J. Rohayem, M. Bolongnesi, and J. R. Hwu, PLOS ONE2014, 9, e91765. 8 Modulation of the tumor microenvironment with organometallic compounds P. J. Dyson 1 1Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology Lausanne (EPFL), CH-1015, Lausanne, Switzerland E-mail: [email protected] This presentation is concerned with the role of metal compounds in the treatment of cancers [1]. The seminar will focus on our own research on ruthenium-based organometallic compounds that are active against chemoresistant and invasive tumors [2]. We show that lead compounds strongly influence the tumor microenvironment and, when used in combination with other drugs, are effective against chemoresistant tumors. These same compounds also show selectivity towards invasive tumors and metastasis. The mechanisms by which these ruthenium-based organometallic compounds exert their pharmacological effects will also be discussed and drug design strategies highlighted [3]. References [1] C. S. Allardyce, P. J. Dyson, Dalton Trans., 2016, 45, 3201-3209. [2] For example see, A. Weiss, X. Ding, J. R. van Beijnum, I. Wong, T. J. Wong, R. H. Berndsen, O. Dormond, M. Dallinga, L. Shen, R. O. Schlingemann, R. Pili, C.-M. Ho, P. J. Dyson, H. van den Bergh, A. W. Griffioen, P. Nowak- Sliwinska, Angiogenesis, 2015, 18, 233-244. [3] For example see, Z. Adhireksan, G. Palermo, T. Riedel, Z. Ma, R. Muhammad, U. Röthlisberger, P. J. Dyson, C. A. Davey, Nature Commun., 2017, 8, 14860. 9 Novel synthetic approaches in medicinal chemistry Valery N. Charushin,1,2 Oleg N. Chupakhin1,2 1I.Y. Postovsky Institute of Organci Synthesis, Ural Branch of Russian Academy of Sciences, Ekaterinburg, Russia 2B.N. Eltsyn Ural Federal University, Ekaterinburg, Russia In the plenary lecture, the novel synthetic approaches to the design of physiologically active compounds are discussed which are being developed in I.Y. Postovsky Institute of Organic Synthesis and B.N. Eltsyn Ural Federal University (Ekaterinburg, Russia). The Ural academic school is known for its prominent achievements in organic and medicinal chemistry, and design of physiologically active compounds including original innovative drugs recently launched into market. 10 Specific inhibitors of myosin ATPase and β-secretase – new prospects for drug development Hans-Joachim Knölker Department of Chemistry, TechnischeUniversität Dresden, Bergstraße 66 01069 Dresden, Germany e-mail: [email protected] We developed a silver(I)-catalyzed cyclization of homopropargylamines to pyrroles which has been applied to the total synthesis of the alkaloids pentabromopseudilin and pentachloropseudilin.1,2 The pentahalogenatedpseudilins represent a novel class of inhibitors for myosin ATPase. The fact that pentachloropseudilin is specific for the inhibition of class-1 myosins whereas pentabromopseudilin is specific for the inhibition of class-5 myosins has been exploited in cell biology.3,4 Alzheimer’s disease (AD) is a neurodegenerative disorder leading to progressive loss of memory and cognitive abilities. In a cooperative project, we have designed potential drugs against AD. A hallmark of AD is the formation of extracellular aggregates of β-amyloid peptides, known as amyloid plaques. These plaques are generated from the membrane-bound amyloid precursor protein (APP) by sequential cleavage of APP involving firstly β-secretase and then γ-secretase. Thus, highly efficient inhibition of the β-secretase enzyme (BACE1) should lead to a potential therapy for AD. Cleavage of APP takes place only when APP and BACE1 are co-internalized into the cell via endocytosis. Based on these findings, we have designed and synthesized a modified lipophilic inhibitor of BACE1 consisting of a tripartite structure, in which each unit exhibits a welldefined function.5–8 Inhibitor Spacer Membrane Anchor Linking of a known BACE1 inhibitor to a membrane anchor via a spacer of defined length leads to a tripartite structure which is transported into the cell by endocytosis and delivered to the site of action where BACE1 is active. Compared to non-lipophilic modified inhibitors, our tripartite structures are more effective by several orders of magnitude – in cell culture as well as in living organisms. In a mouse model, simulating AD, our novel inhibitor reduced the formation of β- amyloid peptides by 50% in only four hours, whereas the known inhibitor showed no effect. References 1. R. Martin, A. Jäger, D. J. Manstein, H. O. Gutzeit, H.-J. Knölker et al., Angew. Chem. Int. Ed. 2009, 48, 8042. 2. R. Martin, C. Risacher, D. J. Manstein, H. O. Gutzeit, H.-J. Knölker et al., Eur. J. Org. Chem. 2014, 4487–4505. 3. E. Rozbicki,

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