Pyrazolyl-benzoxazole derivatives as protein kinase inhibitors. Design and validation of a combinatorial library

The malfunctioning of protein kinases is a hallmark of numerous diseases, for which a satisfactory therapy is missing. We describe the design and synthesis of a kinase targeted library based on a novel 2-(3-phenyl-1H-pyrazol-4-yl)-1,3-benzoxazole scaffold. Ethyl 3-(3-nitrophenyl)pyrazole-4-carboxylate and its 4-nitro regioisomer were bound to trityl chloride resin, saponified with NaOH in MeOH, and amidated with a choice of two o-aminophenols. The resulting N-(2-hydroxyphenyl)amides were cyclized by Mitsunobu reaction to form four variants of the pyrazolyl-benzoxazole core template. Straightforward stannous chloride reduction of the nitro group on solid phase allowed subsequent scaffold derivatization via acylation or sulfonylation of the obtained amino function. Cleavage with TFA gave rise to the final compounds (36 examples).     

A Catalyst Designed for the Enantioselective Construction of Methyl‐ and Alkyl‐Substituted Tertiary Stereocenters

Tertiary methyl‐substituted stereocenters are present in numerous biologically active natural products. Reported herein is a catalytic enantioselective method for accessing these chiral building blocks using the Mukaiyama–Michael reaction between silyl ketene thioacetals and acrolein. To enable remote enantioface control on the nucleophile, a new iminium catalyst, optimized by three‐parameter tuning and by identifying substituent effects on enantioselectivity, was designed. The catalytic process allows rapid access to chiral thioesters, amides, aldehydes, and ketones bearing an α‐methyl stereocenter with excellent enantioselectivities, and allowed rapid access to the C4–C13 segment of (?)‐bistramide A. DFT calculations rationalized the observed sense and level of enantioselectivity.     

Synthesis and preferred all-syn conformation of C3-symmetrical N-(hetero)arylmethyl triindoles

A new series of C(3)-symmetrical N-(hetero)arylmethyl triindoles has been synthesized in a straightforward procedure. The structure and conformation in the solid state have been determined for three derivatives (3, 4, and 6) by X-ray crystallographic analysis. In all three cases, the molecules adopt a tripodal conformation with all of the flexible arms directed towards the same side, thereby delimiting an inner cavity. Compound 6 crystallizes and forms C(3)-symmetric dimeric cagelike complexes. Guest molecules of chloroform and water are confined within the resulting cavities with stabilization by different intermolecular interactions; this highlights the potential of these compounds in the construction of supramolecular systems. A computational analysis has been performed to predict the most stable conformers. As a general trend, a preference for a conformation with all branches directed to the same side has been predicted. Comparison between theoretical and experimental results indicates that the computational level selected for the present study, B3LYP/6-31G*, is able to reproduce both the minimum energy conformations and the rotation barriers about the N--CH(2) bond.     

On variational expressions for quantum relative entropies

Distance measures between quantum states like the trace distance and the fidelity can naturally be defined by optimizing a classical distance measure over all measurement statistics that can be obtained from the respective quantum states. In contrast, Petz showed that the measured relative entropy, defined as a maximization of the Kullback–Leibler divergence over projective measurement statistics, is strictly smaller than Umegaki’s quantum relative entropy whenever the states do not commute. We extend this result in two ways. First, we show that Petz’ conclusion remains true if we allow general positive operator-valued measures. Second, we extend the result to Rényi relative entropies and show that for non-commuting states the sandwiched Rényi relative entropy is strictly larger than the measured Rényi relative entropy for \(\alpha \in (\frac{1}{2}, \infty )\) and strictly smaller for \(\alpha \in [0,\frac{1}{2})\). The latter statement provides counterexamples for the data processing inequality of the sandwiched Rényi relative entropy for \(\alpha < \frac{1}{2}\). Our main tool is a new variational expression for the measured Rényi relative entropy, which we further exploit to show that certain lower bounds on quantum conditional mutual information are superadditive.     

A New Preparative Route of the “Stepped‐Cubane” Tetranuclear Copper(II) Compound, [Cu4(μ2‐OH)2(μ3‐OH)2Cl2(bipy)4]Cl2 · 6H2O

The compound [Cu₄(μ₂‐OH)₂(μ₃‐OH)₂Cl₂(bipy)₄]Cl₂ · 6H₂O ( 1 ) was obtained by recrystallization of [Cu(HB)₂(2, 2′‐bipy)] · H₂O (H₂B = diphenylglycolic acid) from EtOH/CH₂Cl₂ and their structure has been determined by single‐crystal X‐ray analysis. The cationic complex may be described as based on a Cu₄(OH)₄ core with a “stepped cubane” structure. The coordination polyhedron around each copper is a distorted square pyramid. The tetranuclear units are linked in the crystal by C‐H…Cl hydrogen bonds and by π‐π interactions between bipyridine rings. IR data are also presented.     

Thermal and spectroscopic studies on a double-salt-type pyridine–silver perchlorate complex having κ1-O coordinated perchlorate ions

Journal of Thermal Analysis and Calorimetry - A simple synthetic method was developed to prepare 4[Agpy2ClO4]·[Agpy4]ClO4 in a low-temperature decomposition process of [Agpy4]ClO4. A detailed...     

Novel Approach of Evaluating Polymer Nanocomposite Structure by Measurements of the Freezing‐Point Depression

Summary: A novel experimental approach based on the freezing‐point depression of a solvent in a swollen gel has been developed to characterize the structure of nanocomposites. A higher depression in the freezing point has been related with an exfoliated nanocomposite. This increased depression not only depends on the formation of a tighter network but also on the decrease of the size of the solvent cages where the nucleation takes place.

The nucleation process of unfilled and organoclay‐filled natural rubber with the same crosslinking density.     

Challenges of partial discharge diagnostics of low-voltage cables

Partial discharge measurement is one of the most important diagnostic methods to detect local faults in insulation systems. Detection of local faults in low-voltage cables would be attractive for condition assessment of power plant secondary cables. The construction of low-voltage cables is different from the medium and high voltage ones, preventing the direct application of the already developed models and methods. An analysis of partial discharge detection and evaluation methods for low-voltage cable diagnostics are given in this paper. Some laboratory measurement results are also presented and the identified issues are described in this paper.