© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Editor-in-Chief: Natalia Ortúzar
Impact Factor: 2.968
ISI Journal Citation Reports © Ranking: 2014: 19/59 (Chemistry Medicinal); 83/254 (Pharmacology & Pharmacy)
Online ISSN: 1860-7187
June 26, 2015
Editor's Picks: Issue 07/2015
Editor's picks for issue 07: In this issue, a Minireview by Matteo Masetti et al. and a Full Paper by Stefan Günther, Irmgard Merfort, and colleagues illustrate how the latest advances in computational chemistry are solving problems in drug design and discovery. Read more...
Recently Published Articles
- Active Site Mapping of Human Cathepsin F with Dipeptide Nitrile Inhibitors
Janina Schmitz, Norbert Furtmann, Moritz Ponert, Dr. Maxim Frizler, Dr. Reik Löser, Prof. Dr. Ulrike Bartz, Prof. Dr. Jürgen Bajorath and Prof. Dr. Michael Gütschow
Article first published online: 26 JUN 2015 | DOI: 10.1002/cmdc.201500151
Mapping with nitriles: For human cathepsin F, low-molecular-weight inhibitors have not been developed so far. Therefore, a library of 52 dipeptide nitriles, known to interact in a covalent but reversible manner with the active site cysteine, was evaluated for cathepsin F inhibition. With the kinetic data in hand, optimized candidates were designed, synthesized, and tested to improve the activity profile as cathepsin F inhibitors.
- nido-Dicarbaborate Induces Potent and Selective Inhibition of Cyclooxygenase-2
Dr. Wilma Neumann, Dr. Shu Xu, Dr. Menyhárt B. Sárosi, Dr. Matthias S. Scholz, Brenda C. Crews, Kebreab Ghebreselasie, Dr. Surajit Banerjee, Prof. Dr. Lawrence J. Marnett and Prof. Dr. Dr. h.c. Evamarie Hey-Hawkins
Article first published online: 18 JUN 2015 | DOI: 10.1002/cmdc.201500199
Potency boost: Replacement of a phenyl moiety in indomethacin with a nido-dicarbaborate group results in a compound with a novel binding mode and markedly increased inhibitory activity and selectivity for COX-2, with a concomitant increase in stability and water solubility, while maintaining strong hydrophobic interactions in the binding site of the enzyme. This shows nido-dicarbaborate to be a promising pharmacophore for a variety of inhibitors.
- Synthesis, Characterization, and Antileukemic Properties of Naphthoquinone Derivatives of Lawsone
Ryuta Inagaki, Masayuki Ninomiya, Prof. Kaori Tanaka and Prof. Mamoru Koketsu
Article first published online: 18 JUN 2015 | DOI: 10.1002/cmdc.201500189
A new angle on leukemia: We present the facile synthesis of naturally occurring derivatives of lawsone. Results from cytotoxicity assays with HL-60 cells indicate that angular-type naphthoquinones act as antiproliferative agents. The particular efficacy of dunnione is brought about by substantial elevations in intracellular GSSG levels. Dunnione analogues have the potential for further development as chemotherapeutic drugs for the treatment of hyperproliferative disorders.
- Cinnamamide Derivatives for Central and Peripheral Nervous System Disorders—A Review of Structure–Activity Relationships
Dr. Agnieszka Gunia-Krzyżak, Katarzyna Pańczyk, Dr. Anna M. Waszkielewicz and Prof. Henryk Marona
Article first published online: 17 JUN 2015 | DOI: 10.1002/cmdc.201500153
Cinnamamide derivatives have been reported to exhibit antiepileptic, antidepressant, neuroprotective, analgesic, anti-inflammatory, muscle relaxant, and sedative/hypnotic properties, and they are known to act on a variety of targets in the central and peripheral nervous systems, including GABAA, NMDA, prostanoid, opioid, histamine H3, TRP cation channels, voltage-gated potassium channels, and HDACs. Here, literature reports on the structure–activity relationships of cinnamamide-derived biologically active agents are reviewed.
- You have full text access to this OnlineOpen articleFreezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases (pages 1163–1173)
Dr. Franz von Nussbaum, Dr. Volkhart M.-J. Li, Dr. Swen Allerheiligen, Sonja Anlauf, Dr. Lars Bärfacker, Dr. Martin Bechem, Dr. Martina Delbeck, Dr. Mary F. Fitzgerald, Dr. Michael Gerisch, Dr. Heike Gielen-Haertwig, Dr. Helmut Haning, Dagmar Karthaus, Dr. Dieter Lang, Dr. Klemens Lustig, Dr. Daniel Meibom, Prof. Dr. Joachim Mittendorf, Dr. Ulrich Rosentreter, Dr. Martina Schäfer, Prof. Dr. Stefan Schäfer, Dr. Jens Schamberger, Dr. Leila A. Telan and Dr. Adrian Tersteegen
Article first published online: 17 JUN 2015 | DOI: 10.1002/cmdc.201500131
Breathe better: It′s as potent as a low-molecular-weight inhibitor can get! Human neutrophil elastase (HNE) is a driver of pulmonary diseases. We describe the discovery of BAY 85-8501, a small-molecule inhibitor with picomolar in vitro potency against HNE. BAY 85-8501 is currently being assessed in clinical studies for pulmonary diseases.