Learn More
New chemotherapeutics against Dengue virus and related flaviviruses are of growing interest in antiviral drug discovery. The viral serine protease NS2B-NS3 is a promising target for the development of such agents. Drug-like inhibitors of this protease with high affinity to the target are not available at the moment. The present work describes the discovery(More)
The modified integer roundup property (MIRUP) for a linear integer minimization problem means that the optimal value of this problem is not greater than the optimal value of the corresponding LP relaxation rounded up plus one. In earlier papers the MIRUP was shown to hold for the so-called divisible case and some other sub-problems of the one-dimensional(More)
The ongoing Zika virus (ZIKV) outbreak is linked to severe neurological disorders. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target. The 2.7 angstrom; crystal structure of ZIKV protease in complex with a peptidomimetic boronic acid inhibitor reveals a cyclic diester between the boronic acid and(More)
The 3-aryl-2-cyanoacrylamide scaffold was designed as core pharmacophore for inhibitors of the Dengue and West Nile virus serine proteases (NS2B-NS3). A total of 86 analogs was prepared to study the structure-activity relationships in detail. Thereby, it turned out that the electron density of the aryl moiety and the central double bond have a crucial(More)
The dengue virus and related flaviviruses are an increasing global health threat. In this perspective, we comment on and review medicinal chemistry efforts aimed at the prevention or treatment of dengue infections. We include target-based approaches aimed at viral or host factors and results from phenotypic screenings in cellular assay systems for viral(More)
Covalent ligand-target interactions offer significant pharmacological advantages. However, off-target reactivity of the reactive groups, which usually have electrophilic properties, must be minimized, and the selectivity of irreversible inhibitors is a crucial requirement. We therefore performed a systematic study to determine the selectivity of several(More)
The number of dengue virus infections is increasing and the dengue NS2B-NS3 protease is considered a promising target for the development of antiviral therapies. Therefore, reliable and fast screening systems are needed for the discovery of new lead structures. In this chapter, we describe two dengue virus protease assays based on an internally quenched,(More)
In the cutting stock problem (CSP) a given order for smaller pieces has to be cut from larger stock material in such a way that the number of stock material needed is minimal. Based on the classical integer linear programming model the common solution technique consists of solving the corresponding continuous relaxation problem followed by several(More)
The C-terminal β-hairpin of NS2B (NS2Bc) in the dengue virus NS2B-NS3 protease is required for full enzymatic activity. In crystal structures without inhibitor and in the complex with bovine pancreatic trypsin inhibitor (BPTI), NS2Bc is displaced from the active site. In contrast, nuclear magnetic resonance (NMR) studies in solution only ever showed NS2Bc(More)
Several novel betulin derivatives were prepared and evaluated for their antitumor activity. Among others, 3-O-acetylbetulinic aldehyde served as an ideal starting material for the synthesis of 28-acetylenic derivatives that were further transformed into Mannich bases. These hydroxypropargylamines were screened for their antitumor activity in a panel of nine(More)