Arzneimittel-Forschung

A rapid and efficient method was developed for synthesis of 6-acyl-1,3-benzothiazol-2(3H)-one derivatives under microwave irradiation (MWI) conditions. The reaction times were shortened compared to conventional heating. Additionally, we synthesized acetic acid and acetamide derivatives of 1,3-benzothiazol-2(3H)-one, 6-acyl-1,3-benzothiazol-2(3H)-one, 5-chloro-1,3-benzothiazol-2(3H)-one and 6-acyl-5-chloro-1,3-benzothiazol-2(3H)-one with the microwave-assisted method and analyzed their antinociceptive activity with the tail flick, tail clip, hot plate and writhing tests...

In the present study pharmacokinetics and bioequivalence of 2 brands of ciprofloxacin 500 mg were evaluated in 24 healthy male volunteers after a single dose oral administration in an open, randomized, 2-way crossover study.Blood samples were taken before and within 12 h after the administration of the drug. Plasma concentrations of ciprofloxacin were determined by a simple HPLC method with ultraviolet detection. The used method was validated for specificity, accuracy, precision and sensitivity. The mobile phase consisted of 0...

The main objective of this study was to investigate the pharmacokinetic characters of eszopiclone (CAS: 138729-47-2) after single and multiple-dose oral administration in healthy adult Chinese volunteers.In single-dose study, 12 subjects were given oral administrations of 1.5, 3 and 6 mg eszopiclone in an open-label, randomized, crossover fashion. In multiple-dose study, 8 subjects were given 3 mg eszopiclone once daily consecutively for 7 days. Blood samples were collected over 24 h and plasma eszopiclone were determined using a validated liquid chromatography/mass spectrometry (LC/MS/MS) assay...

VEGFR-2 tyrosine kinase inhibitors are currently receiving high interest in drug discovery process as anticancer agents. We have used virtual screening techniques in order to discover new scaffolds that can be used for developing new VEGFR-2 kinase inhibitors.Similarity ensemble approach was used to reduce the chemical space of ZINC database to select a subset of compounds. A validated structure-based pharmacophore was developed and adopted to screen the selected subset. Initial hits mapped to the pharmacophore were filtered using docking and scoring...

A combination of low-dose aspirin (ASA) and a phosphodiesterase inhibitor has been clinically tried for the secondary prevention of atherothrombotic diseases. The in vivo antithrombotic property of ibudilast (CAS 50847-11-5), a phosphodiesterase 4 (PDE4) inhibitor, was evaluated in a photochemically-induced guinea pig carotid artery thrombosis model in combination with low-dose ASA. The time required to decrease the carotid artery blood flow to the reading "zero" was defined as the time to occlusion (TTO) of the artery through thrombogenesis...

No abstract text is available yet for this article.

To discover new bioactive lead compounds for medicinal purposes, herein, sulfone biscompounds bearing dihydrothiazoles (3-9, 14, 15), acrylamide (11), thiazolidinones (12, 13, 20), thiophenes (16, 17) and benzothiophene (19) were prepared and tested for their anticancer activity. The structures of the products were confirmed from elemental analysis as well as spectral data. All the synthesized compounds showed remarkable anticancer activity against human breast cancer cell line especially, compound (3) with IC50 value 23...

G protein-coupled receptor 119 (GPCR 119 (GPR119)) agonists have received considerable attention as a promising therapeutic option for treatment of type 2 diabetes mellitus. GPR119 is one of the GPCRs expressed in pancreatic islet β-cells and its activation enhances stimulation of insulin secretion in a glucose-dependent manner. We have recently described a series of 6-amino-1H-indan-1-ones as potent, selective, and orally bioavailable GPR119 agonists with an amino group that plays important roles not only in their drug-like properties, such as high aqueous solubility, but also in their potent agonistic activity...

A series of phthalazinedione bearing substituted oxadiazole moiety derivatives X(1-7) were synthesized in good yield and evaluated for their possible anticonvulsant activity. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. Their anticonvulsant activities were evaluated by the maximal electroshock induced seizure (MES) and subcutaneous pentylenetetrazole (PTZ) tests. All the tested compounds showed considerable anticonvulsant activities in at least one of the anticonvulsant tests...

The immunomodulatory effects of lactic acid bacteria have been demonstrated previously. In this study, a Lactobacillus plantarum strain was selected and enriched with selenium nanoparticles for use as a new immunomodulating agent in a breast cancer murine model. 30 female inbred BALB/c mice were equally divided into a test group and a control group. For 2 weeks prior to tumor induction, each mouse received a daily oral administration of 2.5×108 CFU/ml of L. plantarum enriched with selenium nanoparticles (SeNPs), and then 1×106 4T1 cells were injected subcutaneously...

To evaluate the impact of single-nucleotide polymorphisms (SNPs) in CYP2C9, MDR1, SLCO1B1 and ABCG2 on the pharmacokinetics of fluvastatin in Chinese participants.A pharmacokinetic study of fluvastatin (single dose 40 mg) was conducted in 12 healthy Chinese volunteers. Plasma concentrations of fluvastatin were determined by a high-performance liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated by non-compartmental method. The SNPs were determined by TaqMan®(MGB) genotyping assay...

Previous studies have documented that substituted 8-oxycaffeines act as inhibitors of human monoamine oxidase (MAO) B. A particularly potent inhibitor among the reported compounds was 8-(2-phenoxyethoxy)caffeine with an IC50 value of 0.383 µM towards MAO-B. In an attempt to improve on the inhibition potency of this compound and to discover highly potent reversible MAO-B inhibitors, in the present study, a series of 8-(2-phenoxyethoxy)caffeine analogues containing various substituents on C4 of the phenoxy ring, were synthesized and evaluated as inhibitors of human MAO-A and -B...

Olanzapine is a widely used agent for the treatment of schizophrenia.The aim of this study was to evaluate bioequivalence of two 10-mg tablet formulations of olanzapine following single oral dose in adult male volunteers.This was a randomized, single-dose, open-label, crossover bioequivalence study. Plasma samples were collected before dosing and at 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0, 72.0, 96.0, 120.0 and 144.0 h after dosing. Plasma concentrations of olanzapine were determined by using a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method...

No abstract text is available yet for this article.

BACKGROUND: Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase developed for the management of hyperuricemia in patients with gout. OBJECTIVE: To investigate the pharmacokinetics and also evaluate the effects of gender and food on the pharmacokinetics of febuxostat in healthy Chinese volunteers. METHODS: A phase I, 3-period study was performed in healthy Chinese male and female subjects. Subjects either received single 40 mg, multiple 40 mg and single 80 mg doses of febuxostat under fasted conditions, or received single 80 mg doses under fed condition...

A specific, sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the simultaneous determination of acrivastine and pseudoephedrine in human plasma samples. Plasma samples were processed and analyzed on a Phenomenex Luna 3 μ CN 100A column (150 mm×2.0 mm) eluted with the mobile phase consisting of methanol and 0.01 mol/L ammonium acetate water solution containing 0.1% formic acid (45:55, v/v) at a flow rate of 0.2 mL/min. The analytes were detected by positive ion electrospray ionization in multiple reaction monitoring mode...

UNLABELLED: OBEJCTIVE: To compare the bioavailability of two 50-mg lamotrigine dispersible tablet formulations (Epilepax®, Ivax-TEVA Argentina Laboratories, Argentina, as a test formulation, and Lamictal®, GlaxoSmithKline, UK, as a reference formulation) in 24 healthy male volunteers. MATERIAL AND METHODS: This study was a randomized, 2-period, 2-sequence crossover design that was open for subjects and investigators, but blind for the bioanalytical lab. Serum samples were obtained over a 120-h interval...

PURPOSE: To synthesize a new series of 5-substituted-3-methylsulfanyl-1H-pyrazole-4-carboxylic acid ethyl esters for their analgesic and anti-inflammatory activity. METHODS: The title compound synthesized by reacting the amino group of 5-amino-3-methylsulfanyl-1H-pyrazole-4-carboxylic acid ethyl ester with acid anhydrides, acid chlorides and phenyl dithiocarbamates. The synthesized compounds were characterized by IR, 1H-NMR and mass spectral data; the purity of the compounds was determined by elemental analysis...

In the fermentation of milk by certain lactic acid bacteria, casein is degraded into bioactive tripeptides shown to lower blood pressure in experimental animal models and in mildly hypertensive humans. This effect is suggested to result mainly in inhibition of angiotensin converting enzyme 1 (ACE-1).Due to the complexity of renin-angiotensin system (RAS), several other enzymes than ACE-1 can participate in the production of vasoactive components. Therefore, in the present study we investigated effects of tripeptides isoleucine-proline-proline (IPP), valine-proline-proline (VPP) and leucine-proline-proline (LPP) on some endothelial enzymes that are important in RAS or otherwise have a role in the endothelial function...

Metronidazole is a BCS (Biopharmaceutics Classification System) class 1 drug, traditionally considered the choice drug in the infections treatment caused by protozoa and anaerobic microorganisms. This study aimed to evaluate bioequivalence between 2 different marketed 250 mg metronidazole immediate release tablets. A randomized, open-label, 2×2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a 7-day washout period. The formulations were administered as single oral dose and blood was sampled over 48 h...