Metabolite analysis of [<Superscript>18</Superscript>F]Florbetaben (BAY 94-9172) in human subjects: a substudy within a proof of mechanism clinical trial

[¹⁸F]Florbetaben ([¹⁸F]BAY 94-9172) is a promising β-amyloid (Aβ) targeted PET-tracer currently in late stage clinical development. [¹⁸F]Florbetaben can assist in the more accurate diagnosis of Alzheimer’s Disease (AD) by non-invasive, in vivo detection of Aβ in the brain. To determine the arterial input function of the PET tracer—as part of a proof of mechanism (PoM) study—arterial samples were drawn from all subjects at predefined time points post injection (p.i.), and the proportion of unchanged tracer [¹⁸F]Florbetaben was determined by HPLC analysis. Plasma metabolite profiles were investigated following intravenous administration of 300 MBq (±60 MBq) of [¹⁸F]Florbetaben to both, patients with AD and healthy controls (HCs), and various methods for processing the blood samples were evaluated. Addition of acetonitrile to plasma samples (obtained from whole blood by centrifugation) and precipitation of proteins resulted in a recovery of more than 90% of the initial radioactivity in the supernatants. High Performance Liquid Chromatography using a polymer-based column (PRP-1) in conjunction with gradient elution was found to be a suitable method of metabolite analysis of [¹⁸F]Florbetaben. HPLC analyses indicated that [¹⁸F]Florbetaben is rapidly metabolized in vivo with an estimated initial half-life of about 6 min. A polar metabolite fraction, consisting presumably of more than one component, and (to a smaller extent) of the demethylated derivative of [¹⁸F]Florbetaben were time-dependently detected in plasma.     

Synthesis of quinazoline based chiral ligands and application in the enantioselective addition of phenylacetylene to aldehydes

Five novel 4-phenylquinazolinols were synthesised in three steps. Their application as ligands in the titanium tetraisopropoxide promoted catalytic enantioselective addition of phenylacetylene to a variety of aldehydes gave propargylic alcohols. Under the optimised reaction conditions, the best enantioselectivity was obtained using l-lactic acid derived 4-phenylquinazolinol and apart from the cyclohexylcarbaldehyde derivative, 16 propargylic alcohols were then synthesised in moderate to excellent enantiomeric excess from 53% to 97%.     

Clarithromycin hydro­chloride 3.5‐hydrate

The absolute configuration was determined for the title compound, C₃₈H₇₀NO₁₃⁺·Cl^?·3.5H₂O. The cation contains a 14‐membered macrocyclic lactone and two sugars, namely cladinose and desos­amine. The six‐membered rings of the sugars adopt chair conformations. The structure is stabilized by strong hydrogen bonds, with O?O distances in the range 2.486 (9)–2.830 (5) Å; other distances are N?O = 2.860 (5), N?Cl = 3.134 (4) and O?Cl = 3.303 (4) Å.     

Synthesis of chiral sulfoximines derived from 3-aminoquinazolinones and their catalysis of enantioselective diethylzinc addition to aldehydes

A series of sulfoxides were sulfoximinated using oxidative addition of 3-aminoquinazolinones by lead tetraacetate in the presence of hexamethyldisilazane. They were applied for the first time in catalytic enantioselective addition to aromatic aldehydes with a product enantiopurity (ee) of 92% in the case of 2-methoxybenzaldehyde.     

Synthesis,Characterization, and Bioactivity of Novel Bicinnolines Having 1‐Piperazinyl Moieties

A number of novel bicinnolines containing piperazine moieties, 4a – o , were synthesized via polyphosphoric acid‐catalyzed intramolecular cyclization of the respective acyl amidrazone derivatives ( 3a – o ). On the other hand, the amidrazones ( 3a – o ) were prepared by reaction of N′,N″‐(biphenyl‐4,4′‐diyl)bis(2‐oxopropane hydrazonoyl chloride) ( 2 ) with the appropriate cyclic sec‐amines in the presence of trimethylamine in absolute ethanol. Structures of the newly synthesized compounds were confirmed by NMR and mass spectral data. The antitumor activity of compounds 4a – o was evaluated in vitro on human breast cancer MDA‐231 by a cell viability assay. Results revealed that compounds 4k , 4n , and 4o exhibit potential cytotoxic effects (>70%) on the cancer cells. Additionally, the antimicrobial activity of compounds 4a – o was evaluated against three clinical microbial strains: Escherichia coli (Gram‐negative bacteria), Staphylococcus aureus (Gram‐positive bacteria), and Candida albicans (fungi/yeast). Results revealed that compounds 4e and 4k exhibit good activity against all three strains included in the study and that compound 4d displays excellent activity against S. aureus strain with a minimum inhibitory concentration value of 0.187 mg/mL.     

Rothe time-discretization method for a nonlinear parabolic p(u) -Laplacian problem with Fourier-type boundary condition and $$L^1$$ -data

Ricerche di Matematica - In this paper, we prove the existence and uniqueness results of entropy solutions to a class of nonlinear parabolic p(u)-Laplacian problem with Fourier-type boundary...     

On the multiplicity of solutions of a simplified tumor growth model with a free boundary

We consider a mathematical model of tumor growth taking into account the spatial structure and include a different phases because of the lack of the nutriments. This model is expressed as a PDE on a spherical domain describing the tumor region. The nonlinearity of this PDE is discontinuous, and our problem can be regarded as a free boundary problem. In fact, the boundary of the tumor and another part in the interior are unknown. We obtain a multiplicity result of solutions together with some properties of the associated free boundaries.     

A transition in the spectral statistics of quantum optical model by different electromagnetic fields

In this paper, we have considered the effects of different quantized electromagnetic fields on the spectral statistics of two-level atoms. The Berry-Robnik distribution and the maximum likelihood estimation technique are used to analyze the effect of the mean photon numbers, the two level atoms numbers and also the quantum number of considered states on the fluctuation properties of different systems which are described by different sets of the Dicke Hamiltonian’s parameters. Our results describe the obvious effect of mean photon number on the spectral statistics and show more regular dynamics when this quantity reaches 700. Also, we observed universality in the spectral statistics of considered systems when the number of two level atoms approaches an unrealistic limit (N _A ~ 200) and there are some suggestions about the effect of the quantum number of selected levels and the atom-field coupling constant on level statistics.     

A new eudesmane type sesquiterpene from Inula viscosa

Investigation of Inula viscosa of Jordanian origin afforded the new sesquiterpene 1beta-hydroxyilicic acid in addition to the known 2beta-hydroxyilicic acid.