Medchemcomm Medicinal Chemistry Communications RSC Publishing Is a Not-For-Profit Publisher and a Division of the Royal Society of Chemistry

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MedChemComm Medicinal Chemistry Communications www.rsc.org/medchemcomm RSC Publishing is a not-for-profit publisher and a division of the Royal Society of Chemistry. Any surplus made is used to support charitable activities aimed at advancing the chemical sciences. Full details are available from www.rsc.org

IN THIS ISSUE ISSN 2040-2503 CODEN MCCEAY 1(1) 1–104 (2010)

Cover Inside cover See Mark E. Bunnage et al., See Rex A. Palmer et al., pp. 45–49. pp. 16–29. The BW202W92 enantiomer is One of the cardinal attributes of a unique biologically active a neural stem cell is its ability to voltage gated sodium channel reliably (and virtually endlessly) blocker; two individual generate the 3 major cell types atropisomers A and B exist. of the brain, namely, neurons Image reproduced by permission (b-tubulin, red), astrocytes (glial of Rex A. Palmer from fibrillary acidic protein, dark blue), Med. Chem. Commun. 2010, 1, 45. and oligodendrocytes (myelin basic protein, green), making them excellent candidates for drug screening. Image reproduced by permission of Mark E. Bunnage from Med. Chem. Commun., 2010, 1, 16.

MEDCHEMWATCH

Downloaded on 03 September 2010 MCW1 MedChemWatch Issue 10: the ofﬁcial newsletter of the European Federation for Medicinal Chemistry (EFMC). Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K

EDITORIALS

11 Welcome to MedChemComm Co-Editors-in-Chief Professor Greg Verdine and Dr Tony Wood introduce the ﬁrst issue of MedChemComm.

This journal is ª The Royal Society of Chemistry 2010 Med. Chem. Commun., 2010, 1, 3–10 | 3 View Online

EDITORIAL STAFF MedChemComm Editor Richard Kelly Medicinal Chemistry Communications Deputy editor Lorena Tomás Laudo www.rsc.org/medchemcomm Senior publishing editor Helen Saxton A peer-reviewed journal publishing medicinal chemistry research, including new studies related to biologically-active chemical or biochemical entities that can act as pharmacological agents with Publishing editors therapeutic potential or relevance. Nicola Burton, Bailey Fallon, Scott Galliflent-Holmes, Frances Galvin, Jonathan Gammon, Ben Merison, MedChemComm is the official journal of the European Federation for Medicinal Chemistry (EFMC). Roxane Owen Publishing assistants Anna Anderson, Jackie Cockrill EDITORIAL BOARD Publisher Co-Editor-in-Chief Sylvie Garneau-Tsodikova Carlos Barbas III Emma Wilson Anthony Wood Regional Associate Editor, Americas La Jolla, CA, US For queries about submitted papers, please contact Sandwich, UK Ann Arbor, MI, US Mark Bunnage Helen Saxton, Senior publishing editor in the first Rob Leurs Sandwich, UK instance. E-mail: [email protected] Co-Editor-in-Chief Regional Associate Editor, Europe Gerhard Ecker Gregory Verdine Amsterdam, The Netherlands EFMC President For pre-submission queries please contact Richard Kelly, Cambridge, MA, US Editor. Email: [email protected] Ming-Qiang Zhang Vienna, Austria Regional Associate Editor, Catherine Peishoff Medicinal Chemistry Communications (print: ISSN Asia-Pacific Collegeville, PA, US 2040-2503; electronic: ISSN 2040-2511) is published monthly Shanghai, China David Rees by the Royal Society of Chemistry, Thomas Graham House, Cambridge, UK Science Park, Milton Road, Cambridge, UK CB4 0WF. Motonari Uesugi All orders, with cheques made payable to the Kyoto, Japan Royal Society of Chemistry, should be sent to RSC Distribution Services, c/o Portland Customer Services, Commerce Way, Colchester, Essex, UK CO2 8HP. INFORMATION FOR AUTHORS Tel +44 (0)1206 226050; E-mail [email protected] 2010 Annual (print+electronic) subscription price: £1173; Full details on how to submit material for publication in This journal is © The Royal Society of Chemistry 2010. US$1876.80. 2010 Annual (electronic) subscription price: MedChemComm are given in the Instructions for Authors Apart from fair dealing for the purposes of research or £1056; US$1689.60 Customers in Canada will be subject to a (available from http://www.rsc.org/authors). Submissions private study for non-commercial purposes, or criticism surcharge to cover GST. Customers in the EU subscribing to should be made via the journal’s homepage: or review, as permitted under the Copyright, Designs and the electronic version only will be charged VAT. If you take an http://www.rsc.org/medchemcomm Patents Act 1988 and the Copyright and Related Rights institutional subscription to any RSC journal you are entitled Regulation 2003, this publication may only be reproduced, to free, site-wide web access to that journal. You can arrange Authors may reproduce/republish portions of their stored or transmitted, in any form or by any means, with the Downloaded on 03 September 2010 access via Internet Protocol (IP) address at www.rsc.org/ip. published contribution without seeking permission prior permission in writing of the Publishers or in the case Customers should make payments by cheque in sterling from the RSC, provided that any such republication is of reprographic reproduction in accordance with the terms payable on a UK clearing bank or in US dollars payable on accompanied by an acknowledgement in the form: of licences issued by the Copyright Licensing Agency in the (Original Citation)–Reproduced by permission of UK. US copyright law is applicable to users in the USA. Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K a US clearing bank. Periodicals postage paid at Rahway, NJ, The Royal Society of Chemistry. USA and at additional mailing offices. Airfreight and mailing The Royal Society of Chemistry takes reasonable care in the in the USA by Mercury Airfreight International Ltd., 365 Blair preparation of this publication but does not accept liability Road, Avenel, NJ 07001, USA. for the consequences of any errors or omissions. US Postmaster: send address changes to Medicinal Chemistry Communications (MedChemComm) c/o Mercury ∞ The paper used in this publication meets the Airfreight International Ltd., 365 Blair Road, Avenel, NJ 07001. requirements of ANSI/NISO Z39.48–1992 (Permanence of Paper). All despatches outside the UK by Consolidated Airfreight. The Royal Society of Chemistry takes reasonable care in the Royal Society of Chemistry: Registered Charity No. 207890. preparation of this publication but does not accept liability for the consequences of any errors or omissions. Inclusion of an item in this publication does not imply endorsement by The Royal Society of Chemistry of the content of the original documents to which that item refers. Advertisement sales: Tel +44 (0) 1223 432246; Fax +44 (0) 1223 426017; E-mail [email protected] For marketing opportunities relating to this journal, contact [email protected] View Online

EDITORIALS

12 MedChemComm in partnership with the European Federation for Medicinal Chemistry Professor Gerhard Ecker, President of the EFMC, highlights the partnership between MedChemComm and the EFMC.

13 Meet the MedChemComm Editorial Board The Editorial Board of MedChemComm introduce themselves.

REVIEWS

16 Small molecule modulation of stem cells in regenerative Downloaded on 03 September 2010 medicine: recent applications and future direction Timothy E. Allsopp,* Mark E. Bunnage* and Paul V. Fish*

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K Small molecules can be used to help drive somatic cell reprogramming, maintain induced pluripotent states and also directly control lineage speciﬁcation and proliferation events. Small molecules have the potential to help enable the development of viable cell therapies and small molecule oral drugs can be envisaged that can control endogenous cell populations to support regeneration.

30 Chemical space as a source for new drugs Jean-Louis Reymond,* Ruud van Deursen, Lorenz C. Blum and Lars Ruddigkeit Methods to enumerate, visualise and virtually screen the ensemble of all possible organic molecules, illustrated by the MQN-map of the chemical universe database GDB-11, offer promising opportunities for drug discovery.

This journal is ª The Royal Society of Chemistry 2010 Med. Chem. Commun., 2010, 1, 3–10 | 5 View Online

CONCISE ARTICLES

Histamine H3 receptor ligands with a 3-cyclobutoxy motif: a novel and versatile constraint of the classical 3-propoxy linker M. Wijtmans,* F. Denonne, S. Celanire, M. Gillard, S. Hulscher, C. Delaunoy, N. Van houtvin, R. A. Bakker, S. Defays, J. Gerard, L. Grooters, D. Hubert, H. Timmerman, R. Leurs, P. Talaga, I. J. P. de Esch and L. Provins* Constraining the classical 3-propoxy linker to a 3-cyclobutoxy moiety reveals a versatile and attractive motif for histamine H3R ligands. 45 An absolute structure template for a unique voltage-gated sodium channel binding site Rex A. Palmer,* Brian S. Potter, Michael J. Leach, Terence C. Jenkins and Babur Z. Chowdhry* The absolute chiral conﬁgurations and important spatial properties for the R-(À)-enantiomer BW202W92 and the pharmacologically much less active S-(+)-enantiomer BW203W92 have been established.

50 Indolequinone-rhodol conjugate as a ﬂuorescent probe for hypoxic cells: enzymatic activation and ﬂuorescence properties Downloaded on 03 September 2010 Hirokazu Komatsu, Hiroshi Harada, Kazuhito Tanabe,* Masahiro Hiraoka and Sei-ichi Nishimoto*

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K Imaging of hypoxic cells was successfully accomplished on the basis of enzymatic reduction characteristics of IQ-R.

54 Design, synthesis, and structure–activity relationships of indole-3-carboxamides as novel water soluble cannabinoid CB1 receptor agonists J. M. Adam,* J. Cairns, W. Caulﬁeld, P. Cowley, I. Cumming, M. Easson, D. Edwards, M. Ferguson, R. Goodwin, F. Jeremiah, T. Kiyoi, A. Mistry, E. Moir, R. Morphy, J. Tierney, M. York, J. Baker, J. E. Cottney, A. K. Houghton, P. J. Westwood and G. Walker A novel CB1 receptor agonist clinical candidate was identiﬁed using high-throughput screening followed by optimization of potency and physico-chemical properties.

6|Med. Chem. Commun., 2010, 1, 3–10 This journal is ª The Royal Society of Chemistry 2010 View Online Downloaded on 03 September 2010 Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K

dt010028_Proof 4pp cover art.indd 7 23/06/2010 10:52:14 View Online

CONCISE ARTICLES

61 Synthesis and selective inhibition of human monoamine oxidases of a large scaffold of (4,5-substituted-thiazol-2- yl)hydrazones Franco Chimenti, Daniela Secci,* Adriana Bolasco, Paola Chimenti, Arianna Granese, Simone Carradori, Melissa D’Ascenzio, Matilde Yanez~ and Francisco Orallo New thiazolylhydrazones as selective human monoamine oxidase inhibitors.

73 Chiral ruthenium polypyridyl complexes as mitochondria- targeted apoptosis inducers Tianfeng Chen, Wen-Jie Mei,* Yum-Shing Wong, Jie Liu, Yanan Liu, Huang-Song Xie and Wen-Jie Zheng* A series of chiral ruthenium polypyridyl complexes have been synthesized and evaluated for their in vitro anticancer activities. L-[Ru(bpy)2(o-tFMPIP)]Cl2$3H2O was identiﬁed as a novel complex that was able to induce mitochondria-mediated apoptosis in melanoma A375 cells through regulation of Bcl-2 family members and activation of caspases.

76 Fluorocarbon oligonucleotide conjugates for nucleic acids delivery Downloaded on 03 September 2010 Guilhem Godeau, Helene Arnion, Christophe Brun, Cathy Staedel and Philippe Barthelemy* The synthesis of ﬂuorocarbon oligonucleotide conjugates

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K (FONs) featuring ﬂuorocarbon hydrophobic and lipophobic moieties is described. The presence of highly ﬂuorinated chains allows the delivery of nucleic acids into human cells.

79 Synthesis and biological activity of new pyridone diaryl ether non-nucleoside inhibitors of HIV-1 reverse transcriptase J. J. Kennedy-Smith,* N. Arora, J. R. Billedeau, J. Fretland, J. Q. Hang, G. M. Heilek, S. F. Harris, D. Hirschfeld, H. Javanbakht, Y. Li, W. Liang, R. Roetz, M. Smith, G. Su, J. M. Suh, A. G. Villasenor,~ J. Wu, D. Yasuda, K. Klumpp and Z. K. Sweeney* New pyridone non-nucleoside reverse transcriptase inhibitors (NNRTIs) were prepared, and several ﬂexible routes to this class of inhibitor were identiﬁed.

8|Med. Chem. Commun., 2010, 1, 3–10 This journal is ª The Royal Society of Chemistry 2010 View Online

CONCISE ARTICLES

84 Effect of particle shape on phagocytosis of CdTe quantum dot–cystine composites Zhisong Lu, Yan Qiao, Xin Ting Zheng, Mary B. Chan-Park and Chang Ming Li* CdTe quantum dot–cystine microcomposites with sphere, rod and needle structures were utilized to investigate the impact of particle shape on macrophage phagocytosis. The shape of particles signiﬁcantly affects the macrophage phagocytosis via the local cell shape at the initial cell–particle contact point.

87 Synthesis and NMDA receptor afﬁnity of dexoxadrol analogues with modiﬁcations in position 4 of the piperidine ring Ashutosh Banerjee, Roland Frohlich,€ Dirk Schepmann and Bernhard Wunsch€ * A series of dexoxadrol analogues has been synthesized and pharmacologically evaluated. Key steps in the synthesis are a hetero-Diels–Alder reaction of the dioxolane-derived imine 10 with Danishefsky’s diene 11 and replacement of the p-methoxybenzyl protective group by a Cbz group.

FREE E-MAIL ALERTS AND RSS FEEDS ADVANCE ARTICLES AND ELECTRONIC JOURNAL Contents lists in advance of publication are available on the web Free site-wide access to Advance Articles and the electronic form via www.rsc.org/medchemcomm – or take advantage of our free of this journal is provided with a full-rate institutional

Downloaded on 03 September 2010 e-mail alerting service (www.rsc.org/ej_alert) to receive subscription. See www.rsc.org/ejs for more information. notiﬁcation each time a new list becomes available. * Indicates the author for correspondence: see article for details. Try our RSS feeds for up-to-the-minute news of the latest Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K research. By setting up RSS feeds, preferably using feed reader software, you can be alerted to the latest Advance Articles Electronic supplementary information (ESI) is available via published on the RSC web site. Visit www.rsc.org/publishing/ the online article (see http://www.rsc.org/esi for general technology/rss.asp for details. information about ESI).

This journal is ª The Royal Society of Chemistry 2010 Med. Chem. Commun., 2010, 1, 3–10 | 9 View Online

AUTHOR INDEX Adam, Julia M., 54 Delaunoy, Christel, 39 Kennedy-Smith, Joshua J., 79 Smith, Mark, 79 Allsopp, Timothy E., 16 Denonne, Frederic, 39 Kiyoi, Takao, 54 Staedel, Cathy, 76 Arnion, Helene, 76 de Esch, Iwan J. P., 39 Klumpp, Klaus, 79 Su, Guoping, 79 Arora, Nidhi, 79 Easson, Morag, 54 Komatsu, Hirokazu, 50 Suh, Judy M., 79 Baker, James, 54 Edwards, Darren, 54 Leach, Michael J., 45 Sweeney, Zachary K., 79 Bakker, Remko A., 39 Ferguson, Morag, 54 Leurs, Rob, 39 Talaga, Patrice, 39 Banerjee, Ashutosh, 87 Fish, Paul V., 16 Li, Chang Ming, 84 Tanabe, Kazuhito, 50 Barthelemy, Philippe, 76 Fretland, Jennifer, 79 Li, Yu, 79 Tierney, Jason, 54 Billedeau, J. Roland, 79 Frohlich,€ Roland, 87 Liang, Weiling, 79 Timmerman, Henk, 39 Blum, Lorenz C., 30 Gerard, Julien, 39 Liu, Jie, 73 van Deursen, Ruud, 30 Bolasco, Adriana, 61 Gillard, Michel, 39 Liu, Yanan, 73 Van houtvin, Nathalie, 39 Brun, Christophe, 76 Godeau, Guilhem, 76 Lu, Zhisong, 84 Villasenor,~ Armando G., 79 Bunnage, Mark E., 16 Goodwin, Richard, 54 Mei, Wen-Jie, 73 Walker, Glenn, 54 Cairns, Jim, 54 Granese, Arianna, 61 Mistry, Ashvin, 54 Westwood, Paul J., 54 Carradori, Simone, 61 Grooters, Luc, 39 Moir, Elizabeth, 54 Wijtmans, Maikel, 39 Caulﬁeld, Wilson, 54 Hang, Julie Q., 79 Morphy, Richard, 54 Wong, Yum-Shing, 73 Celanire, Sylvain, 39 Harada, Hiroshi, 50 Nishimoto, Sei-ichi, 50 Wu, Jeffrey, 79 Chan-Park, Mary B., 84 Harris, Seth F., 79 Orallo, Francisco, 61 Wunsch,€ Bernhard, 87 Chen, Tianfeng, 73 Heilek, Gabrielle M., 79 Palmer, Rex A., 45 Xie, Huang-Song, 73 Chimenti, Franco, 61 Hiraoka, Masahiro, 50 Potter, Brian S., 45 Yanez,~ Matilde, 61 Chimenti, Paola, 61 Hirschfeld, Donald, 79 Provins, Laurent, 39 Yasuda, Dennis, 79 Chowdhry, Babur Z., 45 Houghton, Andrea K., 54 Qiao, Yan, 84 York, Mark, 54 Cottney, Jean E., 54 Hubert, Delphine, 39 Reymond, Jean-Louis, 30 Zheng, Wen-Jie, 73 Cowley, Phillip, 54 Hulscher, Saskia, 39 Roetz, Ralf, 79 Zheng, Xin Ting, 84 Cumming, Iain, 54 Javanbakht, Hassan, 79 Ruddigkeit, Lars, 30 D’Ascenzio, Melissa, 61 Jenkins, Terence C., 45 Schepmann, Dirk, 87 Defays, Sabine, 39 Jeremiah, Fiona, 54 Secci, Daniela, 61 Downloaded on 03 September 2010 Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K

10 | Med. Chem. Commun., 2010, 1, 3–10 This journal is ª The Royal Society of Chemistry 2010 The o;cial EFMC e-newsletter View Online MedChemWatch

10 July 2010

3 EDITORIAL

5 PERSPECTIVE Medicinal Chemistry in the 21th Century

8 SME PRESENTATION iNovacia

9 EFMC AWARDS Camille G. Wermuth Tony Wood Downloaded on 03 September 2010 Klaus Müller

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K 12 LAB PRESENTATION Tony Wood Andreas Bender

15 NEWS FROM SOCIETIES

17 EFMC NEWS

18 EFMC EVENTS View Online

Editor Gabriele Costantino University of Parma, IT

Editorial Committee Erden Banoglu Gazi University, TR Lennart Bunch University of Copenhagen, DK Leonardo Scapozza University of Geneve, CH Wolfgang Sippl University of Halle-Wittenberg, DE Sarah Skerratt Pfizer, Sandwich, UK

Design pupilla grafik web: www.pupilla.eu

Web Design Antalys Sprl web: www.antalys.be Downloaded on 03 September 2010

European Federation for Medicinal Chemistry

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K web: www.efmc.info e-mail: [email protected]

Executive Committee Gerhard F. Ecker President Roberto Pellicciari Past President Koen Augustyns Secretary Rasmus P. Clausen Treasurer Javier Fernandez Member Mark Bunnage Member Péter Mátuys Member

The European Federation for Medicinal Chemistry (EFMC) is an independent association founded in 1970. Free from any political convictions, it represents 24 scientific organisations from 21 European countries and covers a geogra- phical area the size of the USA with a similar scientific population. Its objective is to advance the science of medicinal chemistry by promoting cooperation and encouraging strong links between the national adhering organisations in order to promote contacts and exchanges between medicinal chemists in Europe and around the World. EDITORIALView Online

Dear colleagues,

While most of you have received this newsletter through the usual e-mail alert system, someone may have discovered it by flipping through the pages of the first issue of MedChemComm, the official journal of EFMC, launched by the Royal Society of Chemistry, which is now out with the first scientific contributions. Starting with this issue, MedChemWatch will be distributed together with MedChemComm by keeping its traditional quarterly release. The collaboration between MedChemComm and MedChemWatch is meant to provide a stronger link between cutting-edge scientific dissemination and the activities promoted by EFMC and National Organizations.

The Perspective article in this issue of MedChemWatch is expected to be a particularly interesting one. Gerhard Ecker and Koen Augustyns, President and Secretary of the EFMC, comment on the role of medicinal chemistry in the 21st century, and try to take on the challenge of a redefining the boundaries of medicinal chemistry in the context of emerging new disciplines like chemical Downloaded on 03 September 2010 biology and chemogenomics. I am sure that this Perspective will provoke discussion, and I invite all of you to use the newsletter as a tool for exchange

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K ideas and opinion.

This issue of the newsletter is the last one before the XXI International Symposium of Medicinal Chemistry (ISMC), which will be held in Brussels, September 5-9. The EFMC-ISMC, is the biannual world’s largest Medicinal Chemistry meeting and will be articulated in a series of sessions of exceptional scientific level. You may find the final program at www.ismc2010.org, and you are still on time to register.

The ISMC is also the occasion for our community to recognize, though Awards and Prizes, outstanding scientists who have had a significant impact on medicinal chemistry. MedChemWatch has the honor to present the winners of the Awards and Prizes. In this issue, we present the biographical sketch of Camille Wermuth (University Louis Pasteur Strasbourg and Prestwick Chemicals), winner of the Nauta Award, Tony Wood (Pfizer Global Research and Development), recipient of the UCB Award, and Klaus Müller, winner of the Prous Institute-Overton and Meyer Award for New Technologies in Drug Discovery. We are also proud to present the scientific activity and the lab of the two young winners of the newly established EFMC Prizes, namely Andreas Bender, for the academia, and Antonio Nardi for the industry.

MCW 3 EDITORIAL View Online

The series of the lab presentation is completed by the contribution from iNovacia AB, Stockholm, Sweden.

As usual, the newsletter contains news from the societies, and from the Executive and other Committees of the EFMC. In particular, there are two new functionalities that have been implemented in the official web site of EFMCwww. ( efmc.info) and that I am sure will be of great utility to our community. The first one is the Meeting Calendar which offers a quick way to organize our schedule for the forthcoming months, and provides us with the chance of not missing an interesting event The second functionality is the Job Portal, which can be used to publicize open positions, in both academia and industries.

Lastly, check out the news opportunities launched by EFMC to support the participation of young academic scientists to EFMC organized events.

My best regards,

Gabriele Costantino, Editor of MedChemWatch Downloaded on 03 September 2010 Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K

MCW 4 PERSPECTIVEView Online

Medicinal Chemistry in the 21st Century

by koen augustyns and gerhard ecker

IUPAC defined in 1998 Medicinal Chemistry as a chemistry-based Chemical Biology: discipline, also involving aspects of biological, medical and pharma- An Exciting Challenge For ceutical sciences. It is concerned with the invention, discovery, de- Medicinal Chemists The Royal Society of Chemistry defined sign, identification and preparation of biologically active compounds, Chemical biology as both the use of the study of their metabolism, the interpretation of their mode of ac- chemistry to advance a molecular un- tion at the molecular level and the construction of structure-activity derstanding of biology and the harness- relationships1. Is this still a valid definition or should it be modified? ing of biology to advance chemistry2. It is obvious that there is a great deal

Downloaded on 03 September 2010 Within the past decade a lot of buzz words, such as chemogenomics, chemical genetics, chemical biology, pharmacoepigenetics, pharma- of overlap between these two scientific fields. Certainly the design, synthesis cogenomics, chemical proteomics, systems chemical biology, chem-

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K and characterisation of chemical probes bioinformatics, came up which claim to be independent fields or that are used to study and manipulate disciplines related to drug discovery and development. With this per- biological systems, is best performed spective we would like to provoke a discussion on the future role of by experienced medicinal chemists in medicinal chemistry in the drug discovery and development process the classical definition. as well as give some thoughts on its definition. However, one needs to be aware that good drugs and good chemical probes must meet different criteria3. Therefore the focus of a medicinal chemist in classical medicinal chemistry or in chemical biology will be different. Potency is important in both cases, but after that the requirements diverge significantly. Drugs must prove themselves in clinical trials with a desirable clinical outcome. Next to their pharmacodynamic properties, favourable pharmacokinetic parameters and absence of toxicology are required. The degree of selectivity of a drug for a particular protein tar-

MCW 5 PERSPECTIVE View Online

get doesn’t really matter, as long as the should be supported by e.g. the Inno- targets of these compounds. There- phenotypic outcome is obtained. On vative Medicines Initiative (IMI) from fore, rather than following the long the other hand, high selectivity is abso- the EU. lasting paradigm of starting with the lutely essential for a chemical probe, if target to find the drug, chemogenom- one intends to make firm mechanistic Chemogenomics versus ics should generate drugable targets6. conclusions during target profiling ex- “Classical” Drug Discovery Implementation of these technologies periments. Chemical proteomics is an Chemogenomics, in its broadest sense, certainly will aid in our understanding emerging discipline essential to deter- has been defined as the discovery and how drugs work. With the few of a me- mine the absolute target selectivity of description of all possible drugs to all dicinal chemist, chemogenomics pro- chemical probes. Another difference possible targets5. This is far beyond any vides new tools and techniques which between good drugs and good chemical reality, but in a more realistic scenario will support the medicinal chemist probes is the nature of the interaction still should lead to the identification of scaling his or her lead generation and with the target. There is a strong bias in ligands for all important proteins. With –optimisation capabilities from single pharmaceutical industry that irrevers- this definition chemogenomics makes experiences towards a more broader ible inhibitors would have unfavour- a claim that touches the central aim of and systematic understanding of the able toxicity profiles (although numer- medicinal chemistry. However, state- interaction of small molecules with bio- ous examples prove the contrary). For ments like those above by no means logical systems. Being per se molecular an irreversible chemical probe, the long account for the complexity of any drug driven, also chemogenomics has a lot of lasting chemical knock down of a bio- discovery attempt. Generating selective overlap with medicinal chemistry and logical target will establish the relation- agonists for GPCRs or highly selective thus offers great opportunities for our ship between a molecular target and inhibitors of ABC-transporters remains involvement. the broader biological consequences of quite challenging and is far from being These are two examples of new fields modulating the target. In this respect, solved. A somewhat different definition of research, which have been estab- the use of chemical probes in target of chemogenomics is that it refers to lished and which have considerable Downloaded on 03 September 2010 validation mimics more closely the phe- the perturbation of biological systems overlap with medicinal chemistry and notypic outcome of the drugs that will with the help of small molecules, thus in some cases even have been started

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K be developed than genomic and genetic gaining a holistic understanding of the out of “classical” medicinal chemistry. methods. Needless to say, that in order interaction of these molecules with These new research fields have a merit to reach firm conclusions the chemical complex biological systems. This em- of their own, but also contribute to the probes will have to meet certain quality phasises the more technological part continuous development of what me- criteria4. of chemogenomics with its automation dicinal chemistry is, and what future The art of designing, synthesizing and and miniaturisation attempts and is drugs should look like. While classical characterising good quality chemical more in line with all the other “-omics” drug discovery and development and probes is an exciting challenge for me- approaches. According to this defini- understanding structure activity rela- dicinal chemistry. Especially medicinal tion, chemogenomics is thought to help tionships are still the core of medicinal chemists in the academic community to identifying the respective molecular chemistry, the field has developed a lot, should rise to this challenge since they often have state-of-the-art proteomic fa- cilities at their disposal. This is in con- trast with the lack of expertise and infra- structure to carry out ADME/Tox studies for drug discovery in most academic environments. This part of chemical biology is an area of pre-competitive chemistry that will greatly benefit from public-private collaborations and that

MCW 6 MEDCHEMWATCHView NO.10 Online JULY 2010

including much more than the classical definition indicates.

Medicinal Chemistry and the Innovative Medicines Initiative In 2008, the governing board of IMI – The Innovative Medicines Initiative – approved the strategic research agenda of this World’s largest public private partnership with a volume of 2 billion € for the next 7 years7. The IMI Research Agenda is a multiannual plan developed by the European Technology Platform on Innovative Medicines which identi- fied principal research bottlenecks in pounds inducing cholestasis and their pers recently published an analysis that the biopharmaceutical R&D process profiles at liver transporters” just with greater use of new technologies to vir- and sets forth recommendations to typing in one query! This will revolu- tualise the research process and acceler- overcome these bottlenecks by focusing tionise the way how data can be mined ate clinical development will reduce the on four areas: predicting safety, predict- in medicinal chemistry projects. number of clinical studies by 40% and ing efficacy, knowledge management, There was a lot of discussion within the number of patients in clinical stud- and education and training. Main dis- EFMC that IMI is not made for medici- ies by 65%. Whether real or virtual, fi- ease areas targeted are cancer, brain nal chemists, as medicinal chemistry is nally it comes down to chemical entities disorders, metabolic disease, inflam- considered a core discipline in drug dis- and their interactions, which are driven Downloaded on 03 September 2010 mation and infectious diseases. covery, thus being purely competitive. by the basic laws of physicochemistry. The research projects proposed by However, as outlined above, medicinal EFMC is ready to take the challenge of

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K IMI are broad and multi-disciplinary chemistry knowledge is required in a being the central hub for these develop- and thus cannot be carried out by one lot of areas considered to be precompet- ments. With its symposia, short courses company or within one member state. itive, such as chemical biology and che- and schools, its newsletter and now also One main characteristic of IMI is that mogenomics. Thus, there are many op- with MedChemComm, EFMC provides projects are also ‘precompetitive’ for the portunities for medicinal chemists and perfect conditions for exchanging and pharmaceutical industry. Companies the projects approved in the first call promoting new ideas, exploring new (including SMEs), academics, regula- showed already that there is plenty of grounds and moving beyond estab- tors and patients need to come together space for medicinal chemistry groups. lished thinking! to share resources and expertise to address the challenges of drug discovery Outlook and development (www.imi-europe. The science of medicinal chemistry 1 http://www.chem.qmul.ac.uk/iupac/medchem/ 2 http://www.rsc.org/ScienceAndTechnology/ org). Results and the knowledge and ca- has been used since more than 100 Policy/Bulletins/Issue3/Chemicalbiology.asp pabilities gained from performing such years for the discovery and develop- 3 Kodadek, T. Rethinking screening. Nat. Chem. projects should be made available to the ment of new safe medicines. The field Biol. 2010, 6, 162-165. 4 Frye, S.V. The art of the chemical probe Nat. entire public and private sector. For ex- has become increasingly dynamic and Chem. Biol. 2010, 6, 159-161. ample, the call for an open pharmaco- medicinal chemists face the challenge 5 Müller, G.; Kubinyi, H. Chemogeniomics in logical space (knowledge management of rapidly evolving new technologies. Drug Discovery. Wiley-VCH 2005 6 Szymovski, D.E. Chemical genomics versus call round 2) should lead to an open One of the next large steps will be the orthodox drug development. Drug Discovery data open access system where you can “virtualisation” of the field. The Swiss Today 2003, 8, 157-159. answer questions like “give me all com- branch office of PricewaterhouseCoo- 7 http://imi.europa.eu

MCW 7 SME PRESENTATION View Online

iNovacia

by johan schultz

iNovacia AB, Stockholm, Sweden, was created in 2006 as a The highly experienced HTS team has performed screening scientist buy-out from Biovitrum, which in turn was a spin- campaigns towards all major target classes (GPCRs, ion chan- out in 2001 from Pharmacia Corporation. iNovacia is now nels, enzymes, nuclear receptors) using a wide range of as- an established drug innovator providing discovery services say read-outs (e.g. radioactivity, fluorescence, luminescence, to pharmaceutical and biotech companies in Europe and the absorbance). Primary fragment screening is performed by US. We specialize in providing competitive preclinical can- ligand-based NMR techniques or SPR using a 900+ frag- didates applying technologies to build a strong foundation ment library. for the understanding of structure-activity relationship and predictive ADMET. The hit-to-lead phase where the most promising hit series are selected for further development in full medicinal chem- iNovacia offers a complete coverage of early drug discovery istry programs is a crucial step for a successful drug discov- Downloaded on 03 September 2010 steps from assay development to optimized leads and IND ery project. iNovacia devotes much efforts to ensure that the state. Services include assay development, high-througphut medicinal chemists work on the most promising hit series.

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K screening (HTS), fragment-based screening by NMR and Counter assays and orthogonal assays are employed and our SPR, analytical chemistry, medicinal chemistry at all stages medicinal chemists evaluate the hit series with respect to up to lead optimization, ADMET profiling and biophysical chemical tractability, library expansion tractability, emerging characterization of proteins and compound-protein interac- SAR and IP space. Whenever possible, biophysical assays are tions. performed on hit series representatives in order filter out se- iNovacia scientists are using a range of biophysical tech- ries active via an undesired mechanism and also to obtain niques to decipher and validate mechanism of actions of hit more information on binding modes of compounds from series from HTS The picture shows the high field NMR- promising hit series. Further, analogues are tested and se- laboratory. lected series are expanded by parallel chemistry. Finally, early in-vitro ADME assays are performed before the final priori- The iNovacia HTS compound collection is of highest in- tization of hit series and continuation of the project into the ternational standard, validated by several pharmaceutical lead-generation and lead-optimization phases. companies. It consists of ca 280,000 compounds stored in iNovacia has several modular service offerings that can be DMSO stock solutions under nitrogen at +4°C. To enhance used separately or combined. A combination of the modular downstream success all compounds are carefully selected by offerings can for example cover all steps from assay develop- experienced medicinal chemists applying more than 70 fil- ment to the hit-to-lead phase. iNovacia brings an integrated ters to include and exclude desired and undesired properties, drug discovery organization underpinned by an investment respectively. To enable an early SAR already from primary of 10 Mio EUR in instruments and over 15 years of industrial screening the library is designed so that it includes a bal- track record of delivering drugs into the clinic and onto the anced number of analogues around each scaffold. market.

MCW 8 EFMCView AWARDS Online

MedChemWatch has the honor to acknowledge the winners of the EFMC Awards. In this issue, we present a short biographical sketch of Camille Wermuth, Universi- ty Louis Pasteur Strasbourg and Prestwick Chemicals, winner of the Nauta Award for Pharmacochemistry, Tony Wood, Pfizer Global Research and Development, Sandwich UK, winner of the UCB-Ehrlich Award for Excellence in Medicinal Chemistry and Klaus Müller, Roche-ETH Zurich, winner of the Prous Institute- Overton and meyer Award for New Technologies in Drug Discovery. iNovacia by johan schultz NAUTA AWARD FOR PHARMACOCHEMISTRY Camille G. Wermuth

Camille G. Wermuth was for more than three decades Pro- dicinal Chemistry,” first published in 1996, and now pub- fessor of Organic and Medicinal Chemistry at the Faculty lished in the third edition, was translated into several lan- of Pharmacy at the Louis Pasteur University in Strasbourg, guages, including Japanese and Chinese. France. Besides his academic carreer he was always interested in He became interested in Medicinal Chemistry during his industrial collaborations and drug discovery projects. This Downloaded on 03 September 2010 two years of military service in the French Navy at the “Cen- resulted in the foundation of the medicinal chemistry com- tre d’Etudes Appliquées à la Marine” in Toulon. During this pany Prestwick Chemicals in 1999 in which he put all his

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K time, he worked under the supervision of Dr. H. Laborit, the efforts after retirement from University. He became Presi- scientist who invented artificial hibernation and discovered dent and Chief Scientific Officer of the company and was chlorpromazine. Later he created and headed for 27 years responsible for the success of the company. Over the years the Molecular Pharmacochemistry Unit of the CNRS (“Cen- Prestwick was continuously growing and has now more tre National de la Recherche Scientifique”) in Strabourg. than 30 employees. This unit was original in that it had three areas of responsibility: synthetic organic chemistry, medicinal chemistry and Professor Wermuth has been awarded the Charles Mentzer computer modeling. Prize of the Société Française de Chimie Thérapeutique, the Léon Velluz Prize of the French Academy of Science, and His research has led to the development and synthesis of the Prix de l’Ordre des Pharmaciens by the French Academy many research tools for the Neurosciences and to the devel- of Pharmacy. He is Corresponding Member of the German opment of a new psychotropic drug, minaprine, marketed Pharmaceutical Society, and was nominated Commandeurs in Europe since 1980. His interests focussed on GABAergic des Palmes Académiques. and cholinergic drugs, dopamine D3 receptor ligands, and He has been nominated President of the Division of Chem- CRF receptor antagonists. istry and Human Health of the International Union of Pure and Applied Chemistry (IUPAC). Professor Wermuth is the author and co-author of over 300 peer-reviewed scientific papers. He holds over 60 patents. On the occasion of the 21th International Smposium on Me- He is the author, co-author, and editor of several books or dicinal Chemistry 2010 in Brussels he will be awarded with book chapters. His most recent book, “The Practice of Me- the Nauta Award.

MCW 9 EFMC AWARDS View Online

UCB-EHRLICH AWARD FOR EXCELLENCE IN MEDICINAL CHEMISTRY Tony Wood

Tony Wood is Vice President and Head of Worldwide Pfizer Tony Wood received his BSc in 1987 and PhD in 1990 in Medicinal Chemistry, Pfizer chemistry from Newcastle University, before completing post-doctoral studies with Professor Steven Ley, FRS at Im- Tony Wood has been named as the 2010 winner of the presti- perial College in London working on the total synthesis of gious UCB-Ehrlich Award for Excellence in Medicinal Chem- azadirachtin, one of the most complex molecules ever to have istry. been synthesised, and a project that has only recently been The award is conferred by the European Federation of Me- completed. dicinal Chemistry (EFMC) every two years to acknowledge and recognize outstanding research in the field of medicinal Tony Wood has active interests in many areas of medicinal chemistry in its broadest sense by a young scientist. chemistry including G-protein coupled receptors, cyclic nucleotide processing enzymes, nucleoside and non-nucleoside Tony Wood was selected as the 2010 recipient by an Inter- antiviral drugs, serine and aspartyl protease inhibitors, pro- national Selection Committee, in part, due to his leading the tein transferases and kinases, protein-protein interactions discovery of maraviroc, Pfizer’s breakthrough therapy for and transcription factor regulation. Tony Wood is particularly HIV infection and the first small molecule antagonist of the interested in HIV, HCV and HPV therapies, and molecular CCR5 receptor. In addition to his role guiding Pfizer’s strat- virology from the standpoint of intervention of modulation Downloaded on 03 September 2010 egy for medicinal chemistry, Tony Wood is an active mem- of host targets, in particular the cellular targets necessary for ber of the scientific community and demonstrates a commit- viral fusion and activation of viral transcription.

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K ment to medicinal chemistry education through a number Tony Wood has a highly successful track record of compound of external roles. design and candidate delivery, including broad-spectrum an- tifungal agents, sub-type selective GPCR antagonists and Tony Wood was appointed Head of Worldwide Medicinal potent cyclic nucleotide phosphodiesterase enzyme inhibi- Chemistry at Pfizer in 2008. Prior to this he was Head of tors. He has also been involved in the application of high- Chemistry and Exploratory Medicinal Sciences in Sandwich throughput synthesis and screening technologies to improve from 2007, and Head of Chemistry from 2004. Tony Wood efficiency in drug discovery, and the use of yeast genomics to joined Pfizer (Sandwich) as a Scientist in Discovery Chem- identify new targets for therapeutic intervention. istry in 1992. Over the next eight years, he made a number of contributions to the delivery of development candidates in Tony Wood has held positions on a number of UK funding various projects from within the Sexual Health, Urology, and council review boards such as the BBSRC and EPSRC, and Gastrointestinal therapeutic areas. has recently been elected to the EPSRC’s Council, its top-lev- Tony Wood was appointed to the role of Manager in 1999 el strategic committee. Tony Wood is co-editor in chief of the with responsibility for Anti-Infectives Chemistry, and played new RSC journal, Medicinal Chemistry Communications, a leading role in the discovery of Maraviroc, a CCR5 antago- and was editor of volume 41 of Annual Reports in Medici- nist for the treatment of HIV, for which he was awarded the nal Chemistry in 2006. Tony Wood is an author or inventor RSC Malcolm Campbell Prize in 2005, and was a co-recip- on more than 50 scientific publications and patents, and has ient of the ACS Heroes of Chemistry Prize, the Prix Galien given invited lectures at a number of International Confer- USA and Scrip awards in 2008 and the PhRMA Discoverers ences on Medicinal Chemistry. Tony Wood is also a Visiting Award in 2010. Professor at Newcastle University.

MCW 10 MEDCHEMWATCHView NO.10 Online JULY 2010

PROUS INSTITUTE-OVERTON AND MEYER AWARD FOR NEW TECHNOLOGIES IN DRUG DISCOVERY Klaus Müller

Klaus Müller studied chemistry at the ETH Zurich, where Since early 1998, he has been head of “Science & Technol- he obtained his Ph. D. degree in 1970 with Prof. Albert Es- ogy Relations” in Pharmaceutical Research at Roche, Basel. chenmoser. After postdoctoral work with Prof. Gerhard L. In this function, he has acted as liaison person to both aca- Closs at the University of Chicago, studying radical reactions demic institutions and non-academic external groups and by nuclear magnetic resonance spectroscopy (CIDNP), he has been responsible for the search and early identifica- moved to Harvard University as a visiting lecturer (1971- tion of young talents in chemistry and the life sciences. He 1974) on physical and theoretical organic chemistry. founded the annual “Roche Symposium for Leading Chem- ists of the Next Decade” which rapidly became a honoring By the end of 1974, he joined the scientific staff of the Labo- entry into the CV of those who were selected from all of ratorium für Organische Chemie at ETH Zurich, where he Europe to attend. did his Habilitation in 1977, focusing on molecular structure, energy, reactivity relationships and investigating the He was a board member and Secretary-General of the Roche chemistry of a series of novel strained heterocycles, using Research Foundation from 1999 till its conclusion at the photoelectron spectroscopy end of 2008. Since 1990, he is Extraordinary Professor at the University of Basel, giving advanced courses on “Struc- In 1982, he joined F. Hoffmann-La Roche AG, Basel, in or- ture- and Property-Guided Molecular Design”; a lecture se- Downloaded on 03 September 2010 der to set up a molecular modeling group and to help imple- ries that he also presented at ETH and, as invited “Robert ment biostructural research using macromolecular X-ray B. Woodward Visiting Scholar”, in 2006 in the Department

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K and multi-dimensional NMR spectroscopic analyses. In of Chemistry and Chemical Biology at Harvard University. 1988, he became head of the Section “Computer-Assisted He was promoted in Spring 2005 to “Roche Distinguished and Structural Chemistry, and, in 1991 head of the Depart- Scientist”, one of the first in this novel and highest scientific ments of “Pharma Research Logistics & Support” and “Phar- promotion category of Roche. After his regular retirement ma Discovery Information Management”. in Spring 2009, Klaus Müller continues to be affiliated with Roche as a consultant in chemistry and scientific matter, In these various functions, he has been instrumental in managing among others the new Roche Postdoctoral Pro- implementing and further developing computer-assisted gram. At the same time, he has resumed his teaching activi- molecular modeling and, together with Dr. Paul Gerber, ties at the ETH Zurich where he gives the main upper level developed the MAB force field and the molecular model- “Physical Organic Chemistry” course. ing software “MOLOC” that is today widely used not only at Roche but also in academics and other pharmaceutical Most importantly, over all these years, Klaus Müller has al- companies ways been able to pursue his own research projects targeting the generation and introduction of new concepts in struc- During that period, Klaus Müller pushed computational ture-based lead discovery and optimization. These scientific chemistry, bioinformatics, structure-property analytics and achievements are documented in more than 80 publications correlation methodologies, bringing some of the finest sci- and in over 250 lectures, mostly scientific but also on scientists aboard at Roche and fostering intimate contacts with ence policy matters. academia.

MCW 11 LAB PRESENTATION View Online

EFMC has recently established two Prizes for young researchers in Academia and Industries. The first winners are Andreas Bender, currently Lecturer for Cheminfor- matics, Unilever Centre for Molecular Science Informatics, University of Cambridge (Academia) and Antonio Nardi, currently at Grünenthal, Aachen, Germany (In- dustry) We congratulate with the two winners and offer them space for presenting their scientific activities and their labs.

Antonio Nardi

Winner of the EFMC Prize for Young Researcher in Industry

Dr. Antonio Nardi (1976, married, two children) graduated nels in conditions as diverse as ischemia, chronic obstructive at the faculty of Pharmacy of Pisa University in 2001 (Italy), pulmonary disease (COPD), erectile dysfunction and overac- awarded the same year with the Virdis prize as outstanding tive bladder is currently investigated. One of such research graduate and obtained in 2005 a PhD in medicinal chemistry centre is the Danish Arrhythmia Research Centre (DARC), in from the same university. Throughout the course of his doc- Copenhagen (Denmark) (www.darc.ku.dk), where he is cur- toral studies (2001-2004), first under the supervision of Prof. rently appointed visiting professor in medicinal chemistry. Biagi Giuliana at the Department of Pharmaceutical Sciences in Pisa (www.farm.unipi.it/scieweb) and later under the su- At NeuroSearch, besides the research in the field of BK pervision of Dr. Rodriguez Sarmiento Rosa Maria at the Phar- channel modulators, Dr. Nardi has also extended his scien- maceutical Division, Discovery Chemistry at Hoffmann-La tific interests to positive allosteric modulators of nicotinic Roche AG in Basel (Switzerland) (www.roche.com), Dr. Nardi acetylcholine receptors, for which research programme he had the opportunity to come into contact with diverse drug served as a research chemist leader throughout hit selection Downloaded on 03 September 2010 targets and a number of therapeutic areas. and advanced lead optimisation phase, as well as he had the opportunity to launch a new research programme in drug

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K His main research interest, though, focused on the design discovery, for which he served both as a chemistry leader and and synthesis of structurally novel heterocyclic compounds project leader. This program is to be considered distinctive as modulators of potassium channels, especially the large- in that it is carried out very much in opposition to the most conductance calcium-activated potassium channels (BK), classical paradigms of the modern drug discovery. Part of and their potential therapeutic application in cardiovascular this uniqueness is due to the fact that only high-quality com- diseases. pounds, designed upon a semi-rational principle, are tested His research efforts in this field were then further advanced in a primary in vivo screening and their potential in a given at NeuroSearch A/S (www.neurosearch.com) (Ballerup, therapeutic indication, irrespective of the molecular target(s), Denmark), a biopharmaceutical company focused on unmet is explored by means of systems biology approaches. medical needs and a well-known and recognised pioneer in the BK channel field. Dr. Nardi first served there as a post As per March 1st 2010, Dr. Nardi (antonio.nardi@grunen- doc and subsequently as a research chemist leader for the BK thal.com) has taken up a position within the Preclinical R&D channel programme (2005-2010). division (Medicinal Chemistry) at Grünenthal (www.grunen- His work has resulted in the design of modulators that are thal.com) in Aachen (Germany) where he is currently Asso- currently among the most potent BK channel openers (whose ciate Scientific Director and serves as Project Manager of a status cannot be fully disclosed) as well as in the identifica- research programme aiming at a novel type of ion channel tion of new tool compounds (such as NS11021 and NS13558) modulators. that are currently the basis for scientific collaborations with several American and European universities and research Dr. Nardi has authored more than 15 peer-reviewed articles centres and by which the therapeutic potential of BK chan- and is (co)inventor in more than 20 patent applications.

MCW 12 MEDCHEMWATCHView NO.10 Online JULY 2010

Andreas Bender

Winner of the EFMC Prize for Young Researcher in Academia

10 Years in the Cheminformatics Field – From a Start-Up in Given the independent research possible in this position, and Berlin to a Lectureship in Cambridge under the direction of Jeremy Jenkins, we published more There are times in life where you make consciously the right than a dozen papers during my tenure with Novartis, which decision - but there are also those situations where a seem- allowed me to become an Assistant Professor with the Le- ingly random choice turns out to be the exactly right one in iden / Amsterdam Centre for Drug Research (LACDR) before hindsight. In my case, after studying chemistry at Techni- assuming my current position as a lecturer with Cambridge cal University Berlin and returning from an exchange year University. at Trinity College Dublin, I had the summer after my year abroad off – and having been the decent student I was I decid- Chemogenomics Databases – Millions of Bioactivity Data- ed to look for an internship in a related field. Now, originally I points are at our Disposal for Ligand Design Efforts planned to work in South America in summer, but realizing So why should ligand-based drug design methods be of in- the preparations required for this step I settled for an intern- terest in current days, with more and more crystal structure ship with a cheminformatics start-up close to Berlin instead, popping up in databases every day? Well – not only that both in Hennigsdorf, called CallistoGen. methods are often complementary, but there is simply such a It was the golden time of biotech, back then in summer lot of ligand bioactivity (and more generally, property) data out 2000 (hard to imagine today probably!), and this was the first there which we can (and should) put to good use for future time that I was in touch with ligand-based approaches to drug medicinal chemistry activities. To mention a few numbers: design, giving me a scientific direction for about 10 years by The ChEMBL database at the European Bioinformatics Insti- now. While admittedly being neither a computer expert nor tute (EBI) which was recently released publicly as one of the Downloaded on 03 September 2010 capturing every detail of the virtual screening algorithms I biggest databases of this type, contains more than 560,000 helped to develop at that time, this stint made me realize my compound records with more than 2,700,000 experimental

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K desire to move away from the bench, and to simulations- activities in its current release, spanning more than 7,300 tar- based work from now on. (An accident in my chemistry lab gets. (‘Targets’ in this context might be proteins, but also phe- at home where I nearly lost my eyesight and which kept me notypic readouts such as ‘as ‘walking behaviour’ or ‘change in hospital for over a month might have been a contributing in foot-licking latency’ which are surely some of the more factor as well.) interesting assays to perform). Also other properties, such The nice thing about science is that you can move around as lipophilicity or solubility are of interest to the modelling relatively freely. Hence, for my Master’s Thesis I went to community of course, but I have to say that, personally, I am Goethe University Frankfurt to work with Gisbert Schneider most interested in the factors that contribute to the activity of on a bioinformatics topic; while for my PhD I moved to the chemical matter against protein targets. UK to extend previous work on virtual screening algorithms This type of data can now be used in multiple ways which at the Unilever Centre for Molecular Informatics in Cam- are also pursued in my current research group in Cambridge, bridge / UK with Bobby Glen (which, in fact, is also the place as well as previously in Leiden, termed ‘chemogenomics’ or I returned to just a few months back to assume a position as ‘proteochemometrics’ approaches. These modelling methods a research group leader). What I am very grateful for is a so- take information about the ligand structure, as well as the tar- called ‘Presidential’ Postdoctoral Fellowship with Novartis in get protein, into account in order to make bioactivity predic- Cambridge / MA afterwards – it is a fantastic program, which tions. So why is this useful? Well, imagine you have a series of allows the postdoc to do essentially three years of indepen- compounds, A1, A2, and A3, which you measure against tar- dent research, with all the resources a pharmaceutical com- get 1. At the same time, you know the activities of compounds pany can offer. (‘Presidential’ here refers to the head of the B1, B2 and B3 against target 2 (see Figure 1 for an illustration). research arm of Novartis, not ‘W’ in case you might wonder.) In classical models, you would need to generate two separate

MCW 13 LAB PRESENTATION View Online

by erden banoglu

bioactivity models, one for target 1 and one for target 2, each that is known to be related to modulation of those pathways. of which covers only a relatively small area of chemical space A database of this type, schematically displayed in Figure 2, each. However, if you knew how to translate bioactivities from could be used in a myriad ways in drug discovery: Be it in target 1 into bioactivities against target 2, you would on the the analytical way, by deconvoluting the mechanistic reasons one hand cover more chemical space in your model (namely behind adverse drug reactions, or in the way more relevant chemical space represented by all of the ligands above), and for drug discovery, by rationally choosing ligand chemical fea- on the other hand you would learn to be able to extrapolate tures in order to modulate targets and pathways in a manner between targets 1 and 2. You are now thinking of ligand selec- to reverse the diseased phenotype. Being realistic, our knowl- tivity (or desired promiscuity) profiles against GPCRs? Or bio- edge of bioactive chemical space and pathway annotations is activities against highly resistant mutants of viral enzymes? overall still very limited – still, we have millions of chemog- Then you move into the absolutely right direction - these are enomics data points at our disposal, which we can already use the typical areas where proteochemometrics research could today to make more informed decisions on how to modify be applied, and where we will release prospectively validated compounds to achieve the desired, phenotypic effect. primary research results in the very near future. As illustrated in this example, by employing chemogenomics PhD Students and Postdoctoral Positions Open at the Uni- principles – namely relating proteins by the similarities of lever Centre their ligands - we can use ligand bioactivity data in a much The above are only examples of the amount of knowledge wider way then before. This type of modelling, taking into and the versatility current bioactivity and pathway databases account up to millions of data points, has applications that offer to researchers in the life sciences and I would be very range from receptor deorphanization, to the prediction of happy to contribute with my experience in chemical data polypharmacology of compounds against G-Protein Coupled mining and retrieval to experimental ligand design projects Receptors, to the selection of the right HIV Reverse Tran- in research groups anywhere in the world. Given our recent scriptase Inhibitor active against a particular mutant of this renewal of funding at the Unilever Centre for Molecular In- enzyme. formatics at the University of Cambridge we are currently heavily recruiting about 10 PhD students and postdoctoral From Chemical Space, via Protein Targets and Pathways, to fellows in and around the cheminformatics, chemogenomics Downloaded on 03 September 2010 Phenotypes (and back again) and metabolism areas. If you are interested you are cordially One can even go a step further than this, and not only map invited to visit the Unilever Centre website at http://www-

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K chemical space onto biological space: The next logical step, ucc.ch.cam.ac.uk/ or my personal departmental website at and this is also the plan for future research in my group at http://www.ch.cam.ac.uk/staff/ab.html for further informa- Cambridge University, is to include information also about tion. Also of course, feel free to contact me directly by e-mail phenotypic space in this concept. This would likely involve at [email protected] if you would like to discuss two steps, firstly pathways information mapped onto the tar- options for joint research projects or if you are interested in gets, and secondly including also phenotypic information joining our research groups.

MULT IPLE CONVENTIONAL ONE PROTEOCHEMOMETRIC CHEMICAL SPACE TARGET SPACE PATHWAY PHENOTYPE BIOACTIVITY MODELS MODEL

COMPOUND COMPOUND N HYPOTENSION

N Cl N ANXIETY N H DEPRESSION

N N COMPOUND O VASODILATION COMPOUND HO

HYPOTHERMIA N N

...

Figure 1. While for conventional bioactivity models one model per activity Figure 2. By integrating chemical space with target and pathway annota- class needs to be generated, in proteochemometric models only a single tions, plus a phenotype definition that depends on the particular study, the model, covering all related protein targets at once, is required. Advantages wealth of data available today can be used in both directions: to rationalize are larger coverage of chemical space on the ligand side, plus the ability to phenotypic observations of compounds (such as adverse reactions), as extrapolate to novel, but related targets (the extent of which depends on the well as to influence phenotypes – the objective of every drug discovery pro- precise data given). gramme.

MCW 14 View Online News from the Societies by erden banoglu

second year. It offers young scientists for the discussion of recent advances with a few years of experience in the in the field of Medicinal Chemistry. For pharmaceutical industry and interested the first time HSMC-14 was an EFMC Ph.D. students a broad overview of key sponsored meeting with pronounced disciplines important for modern pre- international participation, represent- clinical drug research. Active participa- ed by invited speakers as well as oral tion in tutorials and a broad variety of presentations and posters from differ- lectures and case histories are impor- ent European countries, among them, tant elements of the course (see also the president of EFMC Prof. Gerhard http://www.swiss-chem-soc.ch/events/ Ecker and the Council member Prof. DIVISION OF MEDICINAL index.cfm ). Danjel Kikelij who also participated in CHEMISTRY OF THE SWISS the round table discussion on: Educa- CHEMICAL SOCIETY NEWS ON ACTIVITIES FOR 2011 tion and Research in Medicinal Chem- dr. hans peter märki istry: The role of Universities and the • March 20-23, 2011 views of industry. In total there were NEWS ON ACTIVITIES FOR 2010 Joint German-Swiss Meeting on Medic- about 150 participants who presented inal Chemistry “Frontiers in Medicinal 5 plenary lectures; 11 main lectures 22 • August 20, 2010 Chemistry”, Saarbrücken, Germany. oral presentations and 100 posters. 2nd International Symposium on The Symposium attracted increased in- “DNA-Encoded Chemical Libraries” Participation in various events which will terest from a considerable number of ETH Zürich be organized to celebrate the UN Interna- Pharmacy and Chemistry students. A Organized by Prof. Dr. Dario Neri tional Year of Chemistry 2011. pre symposium workshop on molecu- • September 16, 2010 lar modeling (1st Hellenic Workshop Downloaded on 03 September 2010 Division of Medicinal Chemistry, oral on Molecular Modeling and Molecular and poster session at the Fall Meeting Docking) was successfully organized

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K of the Swiss Chemical Society for the first time. ETH Zürich HELLENIC SOCIETY OF The Symposium focused on different • September 21-24, 2010 MEDICINAL CHEMISTRY aspects of Medicinal Chemistry bal- The Swiss Chemical Society will orga- ancing from rational design, synthesis nize the ILMAC Scientific Forum at the A report on the 14th Hellenic Sympo- and biological evaluation of new com- Fair Basel (MCH) entitled “From Nylon sium on Medicinal Chemistry in Thes- pounds, molecular modeling and dock- to Nanomaterials. Future Trends in saloniki, Greece ing and drug transporters to screening Polymers”, with a specific section on and semi- or total synthesis of natural September 23 dedicated to Biopolymers The 14th Hellenic Symposium on Me- products as well as to radiopharmaceu- and Polymer Based Drug Delivery. dicinal Chemistry (HSMC-14)) took ticals. The program of the Symposium The program will include a lecture by place in Thessaloniki on 23-25 April, is still available on the website at www. Prof. Alberto A. Gabizon (Hebrew Uni- 2010 and was a successful event. It was helmedchem2010.gr versity, Jerusalem, Israel): “Delivery co-organized by the Hellenic Society The next scientific appointment for of Anticancer Agents by Liposomes: of Medicinal Chemistry (HSMC) and medicinal chemists in Greece will take Nanomedicine in Action”. the Division of Organic and Medicinal place in 2012 in Patras and the two • October 10-15, 2010 Chemistry of the Association of Greek organizations, the Hellenic Society of 9th Swiss Course on Medicinal Chem- Chemists (DOMC-AGC). This series of Medicinal Chemistry and the Division istry, organized by Professor Beat Ernst Symposia follows the tradition of bi- of Organic and Medicinal Chemistry of in Leysin, a pittoresque Swiss moun- annual conferences, established since the AGC are already joining their efforts tain village. This course is held every more than 25 years in Greece, as a forum in setting up the 15th HSMC-2012.

MCW 15 EFMC ISMC 2010 View Online XXIst International Symposium on Medicinal Chemistry

September 5-9, 2010 Brussels, Belgium

INTERNATIONAL ORGANISING COMMITTEE SESSIONS AND SESSION COORDINATORS

Chairmen CAREERS IN MEDICINAL CHEMISTRY RECENT CASE STUDIES IN DD AND DEVELOPMENT Koen Augustyns Graeme Robertson (Sienabiothech, Italy) Gerhard Ecker (University of Vienna and EFMC, VIenna)

(University of Antwerp, Belgium) CHEMICAL APPROACHES TO STEM CELL BIOLOGY MOLECULAR THERAPIES FOR INFLAMMATORY AND Edmond Differding Sheng Ding (The Scripps Research Institute, United States) AUTOIMMUNE DISEASES: ONGOING CLINICAL TRIALS (Formerly with UCB) AND FUTURE PROSPECTS CHEMICAL STRATEGIES FOR FUNCTIONAL PROTEOMICS - Sylviane Muller (CNRS Strasbourg, France) ACTIVITY-BASED PROTEIN PROFILING Members Stephan A. Sieber NATURAL PRODUCTS IN DRUG DISCOVERY Gerhard Ecker (Ludwig-Maximilians-Universität München, Germany) BEYOND CYTOTOXICS AND ANTI-INFECTIVES (University of Vienna & EFMC, Austria) Gloria Serra (Udelar, Uruguay) COVALENT INHIBITORS IN DRUG DISCOVERY Peter Ettmayer Stan Van Boeckel (Schering-Plough, The Netherlands) NEW MEDICINES BEYOND SMALL MOLECULES (Boehringer Ingelheim, Austria) Hans-Ulrich Stilz (Sanofi-Aventis, Germany) Eckhard Ottow EMERGING DRUGS - CASE STUDIES OF RECENTLY (Bayer, Germany) DISCLOSED NEW MEDICINES NOVEL TREATMENTS FOR OBESITY AND METABOLIC Nicholas Carruthers (Johnson & Johnson R&D, United States) DISORDERS Henk Timmerman Roberto Pellicciari (University of Perugia, Italy) (VU Amsterdam, The Netherlands) EMERGING TECHNOLOGIES David Parry (Cyclofluidic, United Kingdom) ONCOLOGY CASE STUDIES Peter Ettmayer (Boehringer Ingelheim, Austria) Downloaded on 03 September 2010 PLENARY LECTURES FINDING THE RIGHT BINDING POCKETS: ALLOSTERIC MODULATORS OF G-PROTEIN COUPLED RECEPTORS FOR PROCESS R&D AND SCALE-UP: CHEMISTRY, CRYSTALS & MORE CHALLENGES AND SUCCESS STORIES � INVITED PLENARY LECTURES NON-CNS DISEASES (ACS Session) Robert A. Fecik (University Of Minnesota, United States) Herbert Stark (Sanofi-Aventis, Germany)

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K �� IUPAC�RICHTER PRIZE LECTURE EFMC AWARD LECTURES FIRST TIME DISCLOSURES SUCCESSFUL STRATEGIES IN LEAD DISCOVERY ë7KH1DXWD$ZDUGIRU3KDUPDFRFKHPLVWU\ Eckhard Ottow (Bayer Schering Pharma, Germany) Hans Peter Maerki (F. Hoﬀmann – La Roche, Switzerland) ë7KH8&%(KUOLFK$ZDUGIRU([FHOOHQFHLQ0HGLFLQDO Chemistry G-PROTEIN COUPLED 7TM RECEPTORS - NEW INSIGHTS TARGETING PATHWAYS ë7KH3URXV,QVWLWXWH2YHUWRQDQG0H\HU$ZDUG INTO THEIR STRUCTURE AND LIGAND RECOGNITION Nicholas Cosford for New Technologies in Drug Discovery Hans Bräuner-Osborne (Burnham Institute for Medical Research, United States) EFMC PRIZE LECTURES (The Danish University of Pharmaceutical Sciences, Denmark) ë3UL]HIRU

SYMPOSIUM SECRETARIAT HOT TOPICS IN CARDIOVASCULAR DISEASES TEACHING MEDICINAL CHEMISTRY Joachim Mittendorf (Bayer Schering Pharma, Germany) EFMC-Teaching & Training Committee

LD Organisation sprl HOT TOPICS IN CNS DISEASES THE CHALLENGES IN DESIGNING MULTIPLE LIGANDS Scientiﬁc Conference Producers Benoît Kenda (UCB, Belgium) DRUGS. THE GOOD, THE BAD AND THE UGLY Rue Michel de Ghelderode 33/2 (ACS Session) 1348 Louvain-la-Neuve, Belgium IMAGING BIOMARKERS John Butera (Wyeth Research, United States) Gilles Tamagnan (Yale School of Medicine, United States) Tel: +32 10 45 47 77 TOXICITY CHALLENGES IN DRUG DESIGN AND Fax: +32 10 45 97 19 INNOVATIVE DRUG DELIVERY SYSTEMS AND STRUCTURE-TOXICITY RELATIONSHIPS [email protected] NANOTECHNOLOGIES (EUFEPS Session) Ferran Sanz (Universitat Pompeu Fabra, Spain) Daan Crommelin (TI Pharma, The Netherlands) VIRTUAL SCREENING AND PROFILING KNOWLEDGE ENABLED DRUG DESIGN Didier Rognan (University of Strasbourg, France) www.ismc2010.org Mark Bunnage (Pﬁzer, United Kingdom)

EFMC H Li Be European Federation Na Mg K Ca Sc Ti V for Medicinal Chemistry Rb Sr Y Zr Nb Cs Ba Lu Hf Ta Fr Ra Lr Rf Db MCWLa Ce Pr Ac Th Pa kvcv16 EFMC ISMC 2010 View Online XXIst International Symposium on Medicinal Chemistry EFMC NEWS September 5-9, 2010 Brussels, Belgium by nele coulier and koen augustyns

EFMC is funding grants for EFMC oral Symposium on Medicinal Chemistry European, but with some from as far ganised events with the aim to support (September 5-9, 2010), the council will away, as Canada and Singapore. Most the participation of young academic elect 6 positions for the Executive Com- participants were from industry, but INTERNATIONAL ORGANISING COMMITTEE SESSIONS AND SESSION COORDINATORS scientists. Upon application, up to 50% mittee. The positions to be elected are there were also two academics. of the registration fee for EFMC-ISMC, president-elect, treasurer, secretary, and The course was a major success, with Chairmen CAREERS IN MEDICINAL CHEMISTRY RECENT CASE STUDIES IN DD AND DEVELOPMENT Koen Augustyns Graeme Robertson (Sienabiothech, Italy) Gerhard Ecker (University of Vienna and EFMC, VIenna) EFMC-ASMC, Frontiers in Medicinal three additional members. The terms for participants enthusiastic about the pro-

(University of Antwerp, Belgium) CHEMICAL APPROACHES TO STEM CELL BIOLOGY MOLECULAR THERAPIES FOR INFLAMMATORY AND Chemistry, EFMC Short Courses or the all the elected EC-members will start on gramme, the quality of the lectures and Edmond Differding Sheng Ding (The Scripps Research Institute, United States) AUTOIMMUNE DISEASES: ONGOING CLINICAL TRIALS EFMC Accredited School will be covered Jan 1st, 2011 and last for two years. The the venue. Most of the lecturers stayed (Formerly with UCB) AND FUTURE PROSPECTS CHEMICAL STRATEGIES FOR FUNCTIONAL PROTEOMICS - Sylviane Muller (CNRS Strasbourg, France) by EFMC. Applications should reach the president-elect will automatically become for the whole of the course, allowing ACTIVITY-BASED PROTEIN PROFILING Administrative Secretariat (administra- President on Jan 1st, 2012. intensive discussions with the partici- Members Stephan A. Sieber NATURAL PRODUCTS IN DRUG DISCOVERY Gerhard Ecker (Ludwig-Maximilians-Universität München, Germany) BEYOND CYTOTOXICS AND ANTI-INFECTIVES [email protected]) at least six weeks prior pants. The course was “evaluated” by (University of Vienna & EFMC, Austria) Gloria Serra (Udelar, Uruguay) to the event and should consist of a CV The EFMC Council will also decide on the means of a questionnaire; with indi- COVALENT INHIBITORS IN DRUG DISCOVERY Peter Ettmayer Stan Van Boeckel (Schering-Plough, The Netherlands) NEW MEDICINES BEYOND SMALL MOLECULES and a short motivation letter. organizers of the 2014 edition of the Inter- vidual contributions scored by partici- (Boehringer Ingelheim, Austria) Hans-Ulrich Stilz (Sanofi-Aventis, Germany) national Symposium on Medicinal Chem- pants for both contents and for quality Eckhard Ottow EMERGING DRUGS - CASE STUDIES OF RECENTLY (Bayer, Germany) DISCLOSED NEW MEDICINES NOVEL TREATMENTS FOR OBESITY AND METABOLIC The EFMC website offers links to the job istry. EFMC is the initiator and sponsor of of the presentation on a scale 1 (poor) Nicholas Carruthers (Johnson & Johnson R&D, United States) DISORDERS Henk Timmerman Roberto Pellicciari (University of Perugia, Italy) portals of EFMC corporate members as this series of symposia, each of which is to 5 (excellent). The score of all contrib- (VU Amsterdam, The Netherlands) EMERGING TECHNOLOGIES well as information on current vacant posi- organized in a European city in collabo- utors was very high with an average of David Parry (Cyclofluidic, United Kingdom) ONCOLOGY CASE STUDIES Peter Ettmayer (Boehringer Ingelheim, Austria) tions. The posting of job offers is free and ration with one or more EFMC National 4.35 for quality of the presentation and PLENARY LECTURES FINDING THE RIGHT BINDING POCKETS: ALLOSTERIC Downloaded on 03 September 2010 is available for any medchem related jobs, Adhering Organization(s). 4.18 for the contents. MODULATORS OF G-PROTEIN COUPLED RECEPTORS FOR PROCESS R&D AND SCALE-UP: CHEMISTRY, CRYSTALS & MORE CHALLENGES AND SUCCESS STORIES in industry as well as academic positions. ISMC 2012 will be held in Berlin. � INVITED PLENARY LECTURES NON-CNS DISEASES (ACS Session) Robert A. Fecik (University Of Minnesota, United States) Herbert Stark (Sanofi-Aventis, Germany)

�� IUPAC�RICHTER PRIZE LECTURE Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K To have your job offer published on the A third short course will be announced EFMC AWARD LECTURES FIRST TIME DISCLOSURES SUCCESSFUL STRATEGIES IN LEAD DISCOVERY website, please fill in the application form EFMC Short Course later this year and will most likely occur ë7KH1DXWD$ZDUGIRU3KDUPDFRFKHPLVWU\ Eckhard Ottow (Bayer Schering Pharma, Germany) Hans Peter Maerki (F. Hoﬀmann – La Roche, Switzerland) ë7KH8&%(KUOLFK$ZDUGIRU([FHOOHQFHLQ0HGLFLQDO available on the site (http://www.efmc. After the success of the first EFMC in April 2011. Chemistry G-PROTEIN COUPLED 7TM RECEPTORS - NEW INSIGHTS TARGETING PATHWAYS info/content.php?langue=english&cle_ Short Course in 2009 at Kasteel Oud ë7KH3URXV,QVWLWXWH2YHUWRQDQG0H\HU$ZDUG INTO THEIR STRUCTURE AND LIGAND RECOGNITION Nicholas Cosford for New Technologies in Drug Discovery Hans Bräuner-Osborne (Burnham Institute for Medical Research, United States) menus=1199870681). Poelgeest near Leiden in the Nether- EFMC PRIZE LECTURES (The Danish University of Pharmaceutical Sciences, Denmark) lands, it was decided to organise fur- ë3UL]HIRU

EFMC-ISMC 2010 XXST NATIONAL MEETING ON MEDICINAL CHEMISTRY 21ST INTERNATIONAL SYMPOSIUM ON MEDICINAL OF THE DIVISION OF ITALIAN CHEMICAL SOCIETY CHEMISTRY

Date: September 5-9, 2010 Date: September 12-16, 2010 Place: Brussels, Belgium Place: Padova, Italy

Website: Website: http://www.ismc2010.org http://www.nmmc2010.sistemacongressi.com/

EFMC-ISMC 2010 will be organised by the Medicinal and Topics: Bioorganic Chemistry Division of Royal Flemish Chemical CNS Medicinal Chemistry Society (KVCV) and the Division for Medicinal Chemistry Epigenetics: A New Pathway to Drug Discovery of the Société Royale de Chimie (SRC), on behalf of the Oncology Medicinal Chemistry European Federation for Medicinal Chemistry (EFMC). Antibacterial and Antiviral Agents This symposium traditionally attracts experts in drug Pharmaceutical Profiling Assays in Drug Discovery and research and development, in particular medicinal and Development synthetic chemists, combinatorial chemists, molecular Drug Design Downloaded on 03 September 2010 modelers, pharmacologists, as well as development chemists. It is is recognized worldwide as one of the leading Contact:

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K Medicinal Chemistry meetings, as proven by its large Francesco Dall’Acqua international attendance. Department of Pharmaceutical Sciences University of Padova Contact: Via Marzolo 5 Dr. Edmond Differding 35131 Padova (Italy) Email: [email protected] Tel: +39 049 827 5708 Fax: +39 049 827 5366 Organised by: Email: [email protected] The European Federation for Medicinal Chemistry (EFMC) and by the Medicinal and Bioorganic Chemistry Division Organised by: of Royal Flemish Chemical Society (KVCV) (Belgium) and Division of Medicinal Chemistry of the Italian Chemical the Société Royale de Chimie (SRC), Medicinal Chemistry Society (Società Chimica Italiana) (Italy) Division (Belgium)

MCW 18 View Online EFMC EVENTS s p o n s o r e d e v e n t s s p o n s o r e d e v e n t s by nele coulier and koen augustyns

18TH EUROPEAN SYMPOSIUM ON QUANTITATIVE SUMMER SCHOOL ON PHARMACEUTICAL ANALYSIS STRUCTURE – ACTIVITY RELATIONSHIPS (SSPA)

Date: 19-24 September 2010 Date: June 13-16, 2010 Place: Rhodes, Greece Place: Rimini, Italy

Website: Website: http://www.euroqsar2010.gr http://www.scpaweb.org/

Topics: The Summer School on Pharmaceutical Analysis (SSPA) Pharmacophore Searching and Virtual Screening is yearly planned under the auspices of the Division of Structure-Based Drug Design - Drugability Medicinal Chemistry of the Italian Chemical Society and the Bioinformatics / Chemoinformatics EFMC (European Federation for Medicinal Chemistry). This Systems Biology and biological complexity three days school is mainly addressed to researchers and Multitarget QSAR PhD students of the Faculties of Pharmacy and Sciences and QSPR for novel biomaterials and regenerative medicine to young scientists from pharmaceutical industries. In silico PhysChem Profiling and ADMET Downloaded on 03 September 2010 Predictive Toxicology and Risk Assessment - Environmental SSPA is organized on a three-year program on the most QSAR advanced analytical methodologies involved into the various

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K Computational Strategies in Agricultural Research stages of the launch of new drugs, from drug discovery (hit Novel QSAR Approaches selection, structure properties relationship), through drug development (ADME/PK properties, biomarkers discovery) Contact: up to formulation and quality control. Congress Secretariat Mr. Gerasimos Kouloumpis Following the 2008 edition focused on ‘Advanced Analytical Zita Congress & Travel Methodologies in Drug Discovery’, and SSPA 2009 Email: [email protected] ‘Advanced Analytical Methodologies in Drug Development’, in 2010 the third year of SSPA covers ‘Advanced Analytical Organised by: Methodologies in Drug Quality Control and Preformulation’. Hellenic Society of Medicinal Chemistry (Greece) Contact person: SSPA Director Prof. Vincenza Andrisano Department of Pharmaceutical Sciences, Alma Mater Studiorum University of Bologna Via Belmeloro 6 40126 Bologna, Italy Tel: +39 (0)51 2099742 Fax: +39 (0)51 2099741 Email: [email protected]

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s p o n s o r e d e v e n t s

9TH SWISS COURSE ON MEDICINAL CHEMISTRY THE 19TH LEIDEN/AMSTERDAM CENTER FOR DRUG RESEARCH SCHOOL ON MEDICINAL CHEMISTRY

Date: October 10-15, 2010 Date: 19-22 October, 2010 Place: Leysin, Switzerland Place: Oegstgeest, The Netherlands

Website: Website: http://www.swiss-chem-soc.ch/smc/leysin/leysin.html http://www.lacdr.nl/events/19th-school-on-medicinal-chemistry

The objectives of the course are to give synthetic chemists, The School encompasses basic and advanced aspects physicochemists, biochemists and pharmacologists a of drug design, pharmacology and toxicology to provide broad and balanced introduction to the background, research chemists in the pharmaceutical industry with the concepts and tools of medicinal chemistry, a science at appro¬priate background for their daily practice. The course the interface of synthetic chemistry, physicochemistry, provides a thorough introduction in pharmacodynamics, phytochemistry, biochemistry, pharmacology and toxicology, pharmacokinetics and toxicology (ADME-Tox). The impact drug metabolism and disposition, molecular modeling and of molecular biology, genomics and molecular modeling on informatics. drug research are also discussed. Newly introduced to the course are cheminformatics and fragment-based design Downloaded on 03 September 2010 Modern preclinical drug research is thus the focus of the approaches. course, which combines dense lectures, tutorials and case In addition, two case histories will give a flavour of chance

Published on 01 July 2010 http://pubs.rsc.org | doi:10.1039/C0MD90006K studies presented by experts from university and industry. and strategy in drug development. Speakers come from both Active participation is encouraged. pharmaceutical industries and academic research institutes; they have been selected for their scientific expertise as well Contact person: Prof. Dr. Beat Ernst as didactic qualities. Tel: +41 61 267 15 50 Fax: +39-0722-3033-13 Contact: Email: [email protected] Ms. Bea Dekker Email: [email protected]

4TH INTERNATIONAL SYMPOSIUM IN ADVANCES IN FRONTIERS IN MEDICINAL CHEMISTRY: “EMERGING SYNTHETIC MEDICINAL CHEMISTRY (ASMC) TARGETS, NOVEL CANDIDATES AND INNOVATIVE STRATEGIES”

To be announced Date: To be announced Place: Stockholm, Sweden

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