Mononuclear photoluminescent salicylaldimato copper(II) complex: synthesis, characterization, mesomorphic investigation and DFT study

A new photoluminescent disc-like copper (II) metallomesogen of the type [CuL2] {H2L = 2,4-bis((E)-((4-(hexadecyloxy)phenyl)imino)methyl)phenol} have been synthesized. The compounds were characterized by elemental analyses, Fourier transform infrared spectroscopy (FTIR), 1H, 13C nuclear magnetic resonance (NMR), ultraviolet – visible spectroscopy (UV – Vis), thermogravimetric analysis (TGA) and high-resolution mass spectrometry. Mesomorphic behavior of the compounds was probed with the help of polarizing optical microscopy (POM) and differential scanning calorimetry (DSC). The organization of the molecules in the mesophase was investigated by X-ray diffraction techniques. The ligand is non-mesogenic but the copper complex exhibited thermally stable columnar mesophases at about 86°C. The copper complex is a blue-light emitter both in solution and in the solid state. The Density Functional Theory (DFT) study was carried out using 6–31 G (d, p) basis set with unrestricted B3LYP level to obtain a stable, optimized structure, which revealed a distorted square-planar geometry for the copper complexes.</p

Odanacatib, a selective cathepsin K inhibitor to treat osteoporosis: safety, tolerability, pharmacokinetics and pharmacodynamics: results from single oral dose studies in healthy volunteers

Aims: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of odanacatib (ODN), a cathepsin K inhibitor, in humans. Methods: Two double-blind, randomized, placebo-controlled, single oral dose studies were performed with ODN (2600mg) in 44 healthy volunteers (36 men and eight postmenopausal women). Results: Adverse experiences (AEs) with single doses of ODN were transient and mild to moderate, with the exception of one severe AE of gastroenteritis. Headache was the most frequent AE. After absorption of ODN (initial peak concentrations 46h postdose), plasma concentrations exhibited a monophasic decline, with an apparent terminal half-life of approximate to 4080h. The area under the curve0-24 hours (AUC024h), concentration at 24 hours (C24h) and maximum concentration (Cmax,overal) increased in a less than dose-proportional manner from 2 to 600mg. Administration of ODN with a high-fat meal led to approximate to 100% increases in AUC024h, Cmax,day1, Cmax,overall and C24h relative to the fasted state, while administration with a low-fat meal led to a approximate to 30% increase in those parameters. Reduction of biomarkers of bone resorption, the C- and N-telopeptides of cross-links of type I collagen, (CTx and NTx, respectively), was noted at 24h for doses 5mg and at 168h postdose for 10mg. In postmenopausal women administered 50mg ODN, reductions in serum CTx of 66% and urine NTx/creatinine (uNTx/Cr) of 51% relative to placebo were observed at 24h. At 168h, reductions in serum CTx (70%) and uNTx/Cr (78%) were observed relative to baseline. Pharmacokinetic/pharmacodynamic modeling characterized the ODN concentration/uNTx/Cr relation, with a modeled EC50 value of 43.8nM and approximate to 80% maximal reduction. Conclusions: Odanacatib was well tolerated and has a pharmacokinetic and pharmacodynamic profile suitable for once weekly dosing