Synthetic procedure to pyrido[2,1-f][1,2,4]triazinium salt and related compounds

N-aminopyridyl ketone salts were reacted with formamide to yield heteroaromatic pyrido[2,1-f][1,2,4]triazinium salts. Upon storage of these products in the presence of water, formation of covalent hydrates have been observed. Reaction of the same starting compound with urethane yielded 3-chloropyrido[2,1-f][1,2,4]triazinium salt which readily reacted with secondary amines to afford 3-amino derivatives. An analogous ring closure reaction of 2-formylaminomethyl- and formaminobenzylpyridine allowed the synthesis of the partially reduced 3,4-dihydropyrido[2,1-f][1,2,4]triazinium compounds. The cyclization procedure was also applied for the synthesis of the related pyrimido[2,1-f][1,2,4]triazinium salt.     

Collective excitations of a degenerate gas at the BEC-BCS crossover

We study collective excitation modes of a fermionic gas of (6)Li atoms in the BEC-BCS crossover regime. While measurements of the axial compression mode in the cigar-shaped trap close to a Feshbach resonance confirm theoretical expectations, the radial compression mode shows surprising features. In the strongly interacting molecular BEC regime, we observe a negative frequency shift with increasing coupling strength. In the regime of a strongly interacting Fermi gas, an abrupt change in the collective excitation frequency occurs, which may be a signature for a transition from a superfluid to a collisionless phase.     

Precision measurements of collective oscillations in the BEC-BCS crossover

We report on precision measurements of the frequency of the radial compression mode in a strongly interacting, optically trapped Fermi gas of (6)Li atoms. Our results allow for a test of theoretical predictions for the equation of state in the BEC-BCS crossover. We confirm recent quantum Monte Carlo results and rule out simple mean-field BCS theory. Our results show the long-sought beyond-mean-field effects in the strongly interacting Bose-Einstein condensation (BEC) regime.     

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.     

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.