Pyridazine derivatives. XIX: Functionalization studies at the 5 position in the 6-phenyl-3(2H)-pyridazinone system

A series of 6-phenyl-3(2H)-pyridazinones bearing different substitution at the 5 position of the pyridazinone ring were prepared in the search for new platelet aggregation inhibitors. The structure of the final compounds was determined on the basis of spectroscopics methods.     

Tetracyclic Thioxanthene Derivatives: Studies on Fluorescence and Antitumor Activity

Thioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline–chromene scaffold were obtained. These compounds were studied for their human tumor cell growth inhibition activity, in the cell lines A375-C5, MCF-7 and NCI-H460. Photophysical studies were also performed. Two of the compounds displayed GI₅₀ values below 10 µM for the three tested cell lines, and structure–activity relationship studies were established. Three compounds presented similar wavelengths of absorption and emission, characteristic of dyes with a push-pull character. The structures of two compounds were elucidated by X-ray crystallography. Two tetracyclic thioxanthenes emerged as hit compounds. One of the two compounds accumulated intracellularly as a bright fluorescent dye in the green channel, as analyzed by both fluorescence microscopy and flow cytometry, making it a promising theranostic cancer drug candidate.     

Synthesis,structural characterization and cytotoxic activity of organotin derivatives of indomethacin

The synthesis, characterization and cytotoxic properties in vitro of tri‐n‐butyltin 1‐(4‐chlorobenzoyl)‐5‐methoxy‐2‐methyl‐1H‐indole‐3‐acetate ( 1 ), tri‐phenyltin 1‐(4‐chlorobenzoyl)‐5‐methoxy‐2‐methyl‐1H‐indole‐3‐acetate ( 2 ), tetra‐n‐butyltin[bis‐1‐(4‐chlorobenzoyl)‐5‐methoxy‐2‐methyl‐1H‐indole‐3‐acetato]distannoxane ( 3 ) and di‐n‐butyltin bis‐1‐(4‐chlorobenzoyl)‐5‐methoxy‐2‐methyl‐1H‐indole‐3‐acetate ( 4 ) are described. These compounds have been characterized by ¹H, ¹³C and ¹¹⁹Sn NMR spectroscopy in solution and ¹¹⁹Sn NMR in the solid state, infrared spectroscopy, elemental analysis and X‐ray diffraction for compound 1 . The growth inhibition effects of compounds 1–4 against the lung adenocarcinoma cell line SK‐LU‐1 as well as the cervical cancer cell line HeLa were determined. Compounds 1 and 2 exhibit cytotoxic activity, whereas compounds 3 and 4 are inactive. Copyright © 2008 John Wiley & Sons, Ltd.     

Sensitivity analysis of the moments of the profit on an Income Protection Policy

The main purpose of this paper is to perform a sensitivity analysis where we quantify and analyse the effects on the mean of the profit on an Income Protection policy and two risk measures of changing the values of the transition intensities. All the calculations carried out are based on a multiple state model for Income Protection proposed in Continuous Mortality Investigation Committee (Continuous Mortality Investigation Reports 1991; 12 ). Within this model, we derive a formula for the mean of the profit, which enables to evaluate it more efficiently. In order to calculate the two risk measures we use the numerical algorithms for the calculation of the moments of the profit proposed by Waters (Insurance: Mathematics and Economics 1990; 9 :101–113). We carry out the sensitivity analysis considering two different situations: in the first situation, we update the premium rates used to calculate the moments of the profit, according to the changes in the values of the transition intensities; in the second one, we do not update the premium rates. Both analyses are of practical interest to insurance companies selling Income Protection policies. Copyright © 2009 John Wiley & Sons, Ltd.     

A manganese(II) coordination polymer with a 3D porous structure: Synthesis,structure, and spectroscopic and magnetic behaviour

A manganese(II) complex with N,N′-bis(carboxymethyl)dithiooxamide (H₄GLYDTO), [Mn(H₂GLYDTO)(H₂O)₂]_n, has been synthesized and characterized by elemental analysis and thermogravimetric analysis, as well as by infrared, electronic and EPR spectroscopy and magnetic susceptibility measurements. The crystal and molecular structure of this complex was determined by single-crystal X-ray structure analysis. The compound shows a 3D porous framework with alternate left- and right-handed helical channels where the manganese(II) ions have an octahedral environment. Variable temperature magnetic measurements reveal the existence of very weak antiferromagnetic interactions through the syn-anti carboxylate bridge, with an exchange parameter of J/k = −0.12 K.     

Characterizing PSPACE with pointers

This paper gives an implicit characterization of the class of functions computable in polynomial space by deterministic Turing machines – PSPACE. It gives an inductive characterization of PSPACE with no ad‐hoc initial functions and with only one recursion scheme. The main novelty of this characterization is the use of pointers (also called path information) to reach PSPACE. The presence of the pointers in the recursion on notation scheme is the main difference between this characterization of PSPACE and the well‐known Bellantoni‐Cook characterization of the polytime functions – PTIME. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)