O-tert-Butyl-L-threonine amide hydrochloride

Chitosan (CS)/metal oxide (MO) nano-carriers have recently attracted attention due to their great integration into several biomedical applications. Herein, CS and dysprosium oxide based bio-nanocomposites (Dy2O3/CuFe3O4/CS) were prepared using a citrate sol-gel route for biomedical settings at large and drug delivery, in particular. The chemical structure, average crystallite size, and surface morphology of Dy2O3/CuFe3O4/CS bio-nanocomposites were characterized using spectroscopic techniques, including FT-IR, PXRD, and SEM. The prepared nano composite's drug loading or release kinetics were investigated by FT-IR, zeta potential (ZP), and ultraviolet-visible spectroscopy (UV-Vis). In the FT-IR spectrum, the peaks in the range of 800-400 cm-1 confirmed the formation of meta-oxides, while amide bands at 1661 and 1638 cm-1 revealed the existence of CS in the bio-nanocomposite. The peaks at 2θ = 35.46 and 28.5, 39.4 indicated the presence and chemical interaction of Dy2O3 and CuFe3O4, respectively. The crystallite size was <20 nm. The model drug used in the loading and in vitro release assays was ciprofloxacin hydrochloride. Ciprofloxacin's CF stretch caused a modest peak to be seen at 1082 cm-1 and changed in zeta potential value from 7.90 mV to 8.88 mV endorsing that the drug had been loaded onto the nanomaterial. The loading efficiency (%) of CIP onto the composite was from 25 to 30 %, calculated from optical density measurements. Different kinetic models, such as zero-order, first-order, Higuchi, Hixon-Crowell, and Korsmeyer-Peppas, were determined to confirm the drug release mechanism. The percent (%) of drug release from the surface of Dy2O3/CuFe3O4/CS in PBS (pH 7.4), acidic (pH 2.2) and basic (pH 9.4) dissolution media were found to be 70, 28 and 20 %, respectively. Drug kinetics showed that mainly the release is fickian type followed "Fick's law of diffusion", slightly deviated from fickian release (dissolution-dependent system). Korsmeyer-Peppas (R2 0.9773, n < 0.4) and Higuchi's (R2 0.9846) models were the best for fitting controlled drug release data. The results revealed that the Dy2O3/CuFe3O4/CS bio-nanocomposite has good potential for a controlled drug delivery system.

Background: 1,2,4-triazoles scaffolds display significant biological activities due to hydrogen bonding, solubility, dipole character, and rigidity. Objective: The core motif of 1,2,4-triazoles plays a vital role in clinical drugs such as Rizatriptan (antimigraine), Ribavirin (antiviral), anastrozole (anticancer), etizolam (anxiolytic), estazolam (anticonvulsant), alprazolam (anti-hypnotic), letrozole (aromatase inhibitor), loreclezole (anticonvulsant), trazadone (antidepressant) etc. Methods: Epoxide ring opening of tert-butyl 6-oxa-3-azabicyclo [3.1.0] hexane-3-carboxylate followed by methylation under basic conditions and de-protection gave the corresponding trans 1-(4- methoxypyrrolidin-3-yl)-1H-1,2,4-triazole hydrochloride salt as the precursor. This precursor on reaction with substituted benzoyl chlorides and benzyl bromides gave the desired amide and amine products. Results: A library of 14 N-substituted pyrrolidine derivatives i.e. trans3-methoxy-4-(1H-1,2,4-triazol- 1-yl) pyrrolidin-1-yl) (phenyl)methanone and trans 1-benzyl-4-methoxypyrrolidin-3-yl)-1H-1,2,4- triazole were prepared. Conclusion: Eight novel amides (6a-h) and six amines (8a-f) derivatives were synthesized using 1-(4- methoxypyrrolidin-3-yl)-1H-1,2,4-triazole 4 salt with substituted benzoyl chlorides and benzyl bromides.

Main pharmacovigilance updates in 2012 are reviewed here. Dabigatran: elderly patients with renal failure are at higher risk of bleeding. Dual renin-angiotensin-aldosterone system blockade comprising aliskiren is harmful. Incretins: low risk of acute pancreatitis. Interaction between fusidic acid and statins: many reports of rhabdomyolysis. Interactions between boceprevir/telaprevir and antiretroviral therapies: complex, but manageable. Citalopram, ondansetron: maximum recommended doses are reduced. Atomoxetine: significant increase in blood pressure and heart rate in a fraction of exposed patients. Agomelatine: elevated liver enzymes are common. Fingolimod: bradycardia and heart blocks after first dose - stronger safety recommendations regarding use in patients with heart conditions and strengthened cardiovascular monitoring.