Literatur

Ohne Zusammenfassung     

Design and Structural Evolution of Matrix Metalloproteinase Inhibitors

Matrix metalloproteinases (MMPs) are involved in a multitude of severe diseases. Despite MMPs being considered druggable targets, past drug-discovery programs have not delivered the anticipated clinical benefits. This review examines the latest structural evolution of small-molecule inhibitors of MMPs, with a focus on the development of novel chemical entities with improved affinity and selectivity profiles. X-ray crystallographic data of the protein targets and cocrystal structures with inhibitors proved to be key for the success achieved during this ambitious endeavor. An evolutionary view on the structural diversity generated for this class of molecules is provided. This encouraging development paves the way for the clinical utilization of this class of highly relevant therapeutic targets. The structure-based design of superior MMP inhibitors highlights the power of this technique and displays strategies for the development of treatment options based on the modulation of challenging drug targets.     

Experimental design considerations in quantification experiments by using the internal standard technique: cholesterol determination by gas chromatography as a case study

An overview on experimental design in quantification experiments using the internal standard technique is described. Particular emphasis is given to the modelling of the relationship analyte/internal standard and the estimation of the optimal amount of internal standard to be used throughout the analytical concentration range by using a uniform shell design with a minimum number of seven experiments. The described approach is demonstrated in the analysis of cholesterol in various reference materials by gas chromatography (GC), using alpha-5 cholestan as internal standard. The outlined approaches can be applied in the determination of any kind of analyte.     

VIER- UND FÜNFGLIEDRIGE PHOSPHORHETEROCYCLEN,XVI 1.3.4.2Λ3-OXADIAZAPHOSPHOLINE

Abstract

Die Kondensation von N ¹-substituierten N-Acetyl-und-Benzoyl-hydrazinen mit P[N(CH₃)₂]₃ oder CH₃P[NCH₃)₂]₂ fuhrt stets zu 3-substituierten 1.3.4.2Λ³-Oxadizaphospholinen, auch wenn der jeweilige Substituent die Bildung von anderen isomeren Fünfringen oder von Isomeren mit größerem Ring oder eine weitergehende Kondensation zuließe. Sie können in die 2.2-Dichloro- und 2-Thioxo-1.3.4.2Λ⁵-Oxadiazaphospholine übergeführt werden.

Condensation of N ¹-substituted N-acetyl and N-benzoyl hydrazines with P[N(CH₃)₂]₃ or CH₃P[N(CH₃)₂] 2 always gives 3-substituted 1.3.4.2Λ3-oxadiazaphospholines, even if the substituent would allow other isomeric five membered or larger ring phosphorus heterocycles to be formed, or the condensation to proceed further. The title compounds can be oxidized to 2.2-dichloro and 2-thioxo 1.3.4.2Λ⁵-oxadiazaphospholines.     

Von Steinkohlenteer bis zu Krebsmedikamenten

When Friedrich Bayer and Johann Friedrich Weskott laid foundation for todays Bayer group, they initially exclusively focused on dyestuffs. However coal tar, which formed the common basis for these dystuffs, offered further opportunities for its application: from crop protection agents across antipyretic medicines up to anti‐cancer drugs. By means of exemplarily chosen chemical substances and their history of development – from the early days until today – the corporate history of Bayer is illustrated.