Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Editor-in-Chief: Natalia Ortúzar
Impact Factor: 3.046
ISI Journal Citation Reports © Ranking: 2013: 18/58 (Chemistry Medicinal); 75/256 (Pharmacology & Pharmacy)
Online ISSN: 1860-7187
Recently Published Articles
- The Discovery of a Highly Selective 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one SIRT2 Inhibitor that is Neuroprotective in an in vitro Parkinson’s Disease Model
Dr. Paolo Di Fruscia, Emmanouil Zacharioudakis, Chang Liu, Dr. Sébastien Moniot, Sasiwan Laohasinnarong, Mattaka Khongkow, Ian F. Harrison, Konstantina Koltsida, Dr. Christopher R. Reynolds, Karin Schmidtkunz, Prof. Dr. Manfred Jung, Dr. Kathryn L. Chapman, Prof. Dr. Clemens Steegborn, Prof. David T. Dexter, Prof. Michael J. E. Sternberg, Prof. Eric W.-F. Lam and Dr. Matthew J. Fuchter
Article first published online: 13 NOV 2014 | DOI: 10.1002/cmdc.201402431
Hit discovery: Through ligand-based virtual screening validation, ICL-SIRT078, a cell-active substrate-competitive SIRT2 inhibitor with a Ki value of 0.62±0.15 μM and more than 50-fold selectivity against SIRT1, 3 and 5 was identified. In addition, ICL-SIRT078 shows a significant neuroprotective effect in a lactacystin-induced model of Parkinsonian neuronal cell death in the N27 cell line. ICL-SIRT078, or an optimised derivative thereof, warrants further investigation as a neuroprotective agent in in vivo models of Parkinson’s disease.
- From Ergolines to Indoles: Improved Inhibitors of the Human H3 Receptor for the Treatment of Narcolepsy
Dr. Yves P. Auberson, Dr. Thomas Troxler, Dr. Xuechun Zhang, Dr. Charles R. Yang, Dr. Dominik Feuerbach, Dr. Yu-Chih Liu, Dr. Bharat Lagu, Dr. Mark Perrone, Dr. Lijun Lei, Dr. Xiaoxia Shen, Dr. Dushan Zhang, Dr. Chunxiu Wang, Dr. Tie-Lin Wang, Dr. Karin Briner and Dr. Mark G. Bock
Article first published online: 12 NOV 2014 | DOI: 10.1002/cmdc.201402418
Better than caffeine! Simplification of the ergoline scaffold of the H3 receptor antagonist 1 led to a series of indoles with improved pharmacological properties and better chemical accessibility. A combined pharmacodynamic, pharmacokinetic, and receptor occupancy evaluation led to the selection of 15 m, the wakefulness-enhancing properties of which were demonstrated by EEG measurements in rats.
- Oxidation Potentials of N-Modified Derivatives of the Analgesic Flupirtine Linked to Potassium KV7 Channel Opening Activity But Not Hepatocyte Toxicity
Christian J. Lemmerhirt, Mirko Rombach, Dr. Anja Bodtke, Prof. Dr. Patrick J. Bednarski and Prof. Dr. Andreas Link
Article first published online: 12 NOV 2014 | DOI: 10.1002/cmdc.201402442
Oxidation–activation–toxicity? The connection between activity, toxicity, and oxidation potential of the pain killer flupirtine was investigated. N-Modified analogues of flupirtine displayed varying oxidation potentials that appeared to be linked to potassium channel opening activity but not to in vitro hepatotoxicity. These data suggest that oxidative metabolites of flupirtine contribute to the mechanism of action, but not to liver toxicity.
- Evaluating p97 Inhibitor Analogues for Their Domain Selectivity and Potency against the p97–p47 Complex
Dr. Chen-Jie Fang, Dr. Lin Gui, Dr. Xiaoyi Zhang, Derek R. Moen, Dr. Kelin Li, Dr. Kevin J. Frankowski, Dr. Henry J. Lin, Dr. Frank J. Schoenen and Dr. Tsui-Fen Chou
Article first published online: 6 NOV 2014 | DOI: 10.1002/cmdc.201402420
Grade-AAA inhibitors: We carried out a structure–activity relationship study of 200 p97/valosin-containing protein inhibitor analogues for the p97 D1 and D2 domains, as well as the p97–p47 complex. Our studies provide potential starting points for the development of D1-domain-selective and p97–p47- complex-specific inhibitors.
- Development of Second-Generation Small-Molecule RhoA Inhibitors with Enhanced Water Solubility, Tissue Potency, and Significant in vivo Efficacy
Sheng Ma, Dr. Jing Deng, Baoli Li, Xiujiang Li, Zhaowei Yan, Dr. Jin Zhu, Gang Chen, Prof. Zhong Wang, Prof. Hualiang Jiang, Prof. Liyan Miao and Prof. Jian Li
Article first published online: 5 NOV 2014 | DOI: 10.1002/cmdc.201402386
Whoa RhoA! Second-generation small-molecule RhoA inhibitors were obtained by structural modifications to the aniline nitrogen and acid side chain of lead compounds. Among 32 compounds synthesized and tested in biological assays, one compound was identified as the most potent and water soluble, showing good in vitro and in vivo efficacy.