Regioselective Synthesis, Structural Characterization, and Antiproliferative Activity of Novel Tetra-Substituted Phenylaminopyrazole Derivatives

A small library of highly functionalized phenylaminopyrazoles, bearing different substituents at position 1, 3 and 4 of the pyrazole ring, was prepared by the one pot condensation of active methylene reagents, phenylisothiocyanate and substituted hydrazine (namely, methyl- and benzyl-hydrazine). The identified reaction conditions proved to be versatile and efficient. Fur-thermore, the evaluation of alternative stepwise protocols affected the chemo- and re-gio-selectivity outcome of the one-pot procedure. The chemical identity of two N-methyl pyrazole isomers, selected as prototypes of the whole series, was unambiguously identified by means of NMR and mass spectrometry studies. Additionally, semiempirical calculations provided a structural rationale for the different chromatographic behaviour of the two isomers. The prepared tetra-substituted phenylaminopyrazoles were tested in cell-based assays on a panel of cancer and normal cell lines. The tested compounds did not show any cytotoxic effect on the selected cell lines, thus supporting their pharmaceutical potentials

A rare case of Prinzmetal angina 3 days after coronary artery stenting with a second-generation drug-eluting stent.

Non previsto

Combined adenocarcinoma\u2013atypical carcinoid of the lung. Targeted Next-Generation Sequencing (NGS) suggests a monoclonal origin of the two components

Combined neoplasms of the lung are defined by the WHO classification as an admixture of a small or large cell neuroendocrine carcinoma and a non-neuroendocrine component. However, rare cases of carcinoids combined with a non-neuroendocrine component have been described. These tumor types are not included as a specific entity in the WHO classification of pulmonary neoplasms and their pathogenesis is still unknown. We describe the clinico-pathologic and molecular features of a mixed (combined) lung neoplasm composed of adenocarcinoma and atypical carcinoid. The NGS analysis of the two different tumor components shows a similar molecular profile suggesting their monoclonal origin from a transformed stem/progenitor tumor cell which acquires a divergent differentiation during its development and progression. We also suggest the use of the recently proposed term of mixed neuroendocrine/non-neuroendocrine neoplasm (MiNEN) to define mixed (combined) neoplasms of the lung, because it seems to better cover the wide spectrum of different possible combinations of neuroendocrine and non-neuroendocrine components

Towards a Dynamic Logic of Gradual Normativity and Norm Adherence

Norms and accountability in multi-agent societies Authors: Kibble, Rodger Norms and plans as unification criteria for social collective