View Online 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). 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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. 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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 39 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