Mevlüt Ertan

6-Benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-onessubstituted with ibuprofen: synthesis, characterizationand evaluation of anti-inflammatory activity

In this study, the synthesis of 3-[1-(4-(2-methylpropyl)phenyl)ethyl]-1,2,4-triazole-5-thione (2) and its condensed derivatives 6-benzylidenethiazolo[3,2-b]-1,2, 4-triazole-5(6H)-ones (2a-u) are described. The structures of the compounds were elucidated by spectral and elemental analysis. In the pharmacological studies, anti-inflammatory activities of these compounds have been screened. Among the compounds examined, the compounds 2 and 2g possessed the most prominent and consistent activity. In gastric ulceration studies the synthesized compounds were generally found to be safe at a 200 mg/kg dose level.

Thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one substituted with ibuprofen: Novel non-steroidal anti-inflammatory agents with favorable gastrointestinal tolerance

In an effort to establish new candidates with improved analgesic and anti-inflammatory activities and lower ulcerogenic risk, a series of thiazolo[3,2-b]-1,2,4-triazole-5(6H)-one derivatives of ibuprofen were synthesized. All compounds were evaluated for their in vivo anti-inflammatory and analgesic activities in mice. Furthermore, the ulcerogenic risks of the compounds were determined. In general, none of the compounds represent a risk for developing stomach injury as much as observed in the reference drugs ibuprofen and indomethacin. The compounds carrying a 3-phenyl-2-propenylidene (1a), (biphenyl-4-yl)methylidene (1f) and (1-methylpyrrol-2-yl)methylidene (1n) at the 6th position of the fused ring have been evaluated as potential analgesic/anti-inflammatory agents without a gastrointestinal side effect. These new compounds, therefore, deserve further attention to develop new lead drugs.

Second Derivative Spectrophotometric Determination of p-Aminophenol in the Presence of Paracetamol

Abstract A second derivative spectroscopic method for the determination of p-aminophenol in paracetamol powder is described. Second derivative absorbance (d2A/dλ2) values were measured at 223.8 nm (Δ = 4.2 nm) where p-aminophenol showed derivative responses obeying Beers Law but paracetamol had negligible derivative absorption. The concentrations of p-aminophenol solutions prepared in 0.1 N HCl (0.12–7.61 mcg/ml), containing constant amounts of paracetamol (20 mcg/ml) related linearly with the d2A/dλ2 values and gave a straight line (r = −0.9999). The method allowed determination of 0.5% to 38% of p-aminophenol in paracetamol without prior separation, it is rapid, precise and accurate.

Novel thiazolo[3,2-b]-1,2,4-triazoles derived from naproxen with analgesic/anti-inflammatory properties: Synthesis, biological evaluation and molecular modeling studies.

3-Substituted-1,2,4-triazole-5-thiones are versatile synthetic intermediates for the preparation of several biologically active N-bridged heterocyclic compounds, given that they have two reactive sites, thiocarbonyl and an amine nitrogen (N1/N4). For several years, our interest has focused on the synthesis of novel heterocyclic systems derived from 3-substituted-1,2,4-triazole-5-thiones having analgesic/anti-inflammatory activity. In this study, a series of novel thiazolo[3,2-b]-1,2,4-triazole-6(5H)-one derivatives bearing naproxen was synthesized and evaluated for their in vivo analgesic and anti-inflammatory properties in acute experimental pain and inflammation models. The compounds were also tested for their ulcerogenic potential. Our findings showed that all the newly synthesized derivatives attenuate nociception and inflammation compared with a control. All the synthesized compounds exhibited much lower ulcerogenic risk than the standard drugs indomethacin and naproxen. Some compounds with significant analgesic and/or anti-inflammatory activities as well as low ulcer scores were further evaluated for in vitro COX-1 and COX-2 inhibitory potential in a COX-catalyzed prostaglandin biosynthesis assay. Among the tested compounds, compound 1q showed the highest selectivity index (SI) of 4.87. The binding mode for some of the tested compounds to the cyclooxygenase (COX) enzymes was predicted using docking studies.

Condensed Heterocyclic Compounds: Synthesis and Antiinflammatory Activity of Novel Thiazolo[3,2-a]pyrimidines

In this study, thirty six new 2‐benzylidene‐7‐methyl‐3‐oxo‐5‐phenyl‐2,3‐dihydro‐5H‐thiazolo[3,2‐a]pyrimidine‐6‐carboxylic acid methyl esters were synthesized and characterized by spectral, crystallographic, and elemental analysis. The antiinflammatory activity of the compounds was tested by the carrageenan hind paw edema test. It was found that compound 6a having a 2‐methoxyphenyl group at position 5 and a benzylidene group at position 2 was the most potent compound in this series. All the compounds that were tested for ulcer activity gave positive results.

Synthesis, structural elucidation and pharmacological properties of some 5-acetyl-3,4-dihydro-6-methyl-4-(substituted phenyl)-2(1H) -pyrimidinones.

In this study, the synthesis of some new 5-acetyl-3,4-dihydro-6-methyl-4-(substituted phenyl)-2(1H)-pyrimidinones has been reported. The compounds were prepared by the Biginelli reaction of acetylacetone with aromatic aldehydes and urea. The structures of the compounds were characterized by UV, IR, 1H NMR, 13C NRM, mass spectra and elementary analysis. The calcium antagonistic activity of these compounds was tested in vitro on rat ileum precontracted with 4 x 10(-3) M barium chloride.

3,4-Diaminopyridine in Childhood Myasthenia: Double-Blind, Placebo-Controlled Trial:

Eleven patients with congenital and five with juvenile myasthenia gravis, aged 5 to 24 years, were given 3,4-diaminopyridine in a double-blind, placebo-controlled, crossover study. Clinical improvement was observed in 5 of 11 congenital myasthenia patients, and placebo effect, in 3 of 11. Juvenile myasthenia patients did not respond. Single-fiber electromyographic studies did not reveal any changes correlating with the clinical status of the patient. This study demonstrates the importance of double-blind and placebo-controlled studies to determine the effect of 3,4-diaminopyridine in congenital myasthenia. This drug may have different effects on various presynaptic and postsynaptic defects of neuromuscular transmission resulting in congenital myasthenia syndromes. (J Child Neurol 1996;11:458-461).

Development and Validation of a Capillary Electrophoretic Method for the Determination of Degradation Product in Naphazoline HCl Bulk Drug Substance

Abstract In this study a capillary electrophoretic method is described for the identification and quantitation of the main degradation product napthylacetyletylenediamine (NAED) in naphazoline HCl bulk drug. The effect of temperature, operating voltage, and electrolyte concentration on the resolution was determined by using a multivariate experimental design. The separation was achieved at 15 kV, on a 70 cm (62 cm effective) × 75 μm I.D. capillary at 20°C using 0.1 M, pH 3 phosphate buffer as background electrolyte. The method was validated and satisfactory specificity, linearity, precision, and accuracy results were obtained.

Investigation of antioxidant properties of some 6-(α-aminobenzyl)thiazolo[3,2-b]-1,2,4-triazole-5-ol compounds

Promising antiinflammatory activity together with low ulcerogenic properties of some Michael addition products of thiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones which have been synthesized in our previous study, prompted us to investigate their antioxidant properties. Since compound Ib has both antioxidant and antiinflammatory activities beside the lowest ulcerogenic incidence, it was selected for investigation of its inhibitory effect on various cyclooxygenase ezymes. It was found that while it did not inhibit cyclooxygenase-1 (COX-1) enzyme, there was a small inhibitory effect (17%) on COX-2 enzyme. We concluded that the diminished harmful effects on the stomach of this novel antiinflammatory compound were related to its antioxidant properties since it is ineffective on COX-1 enzyme. In conclusion, the compounds having both antioxidant and antiinflammatory activities with a lack of COX-1 enzyme inhibitory effect may improve the gastrointestinal safety profile of such compounds.

Protective effects of thiazolo[3,2-b]-1 ,2,4-triazoles on ethanol-induced oxidative stress in mouse brain and liver.

A series of 3-[1-(4-(2-methylpropyl) phenyl) ethyl]-1,2,4-triazole-5-thione (I) and its bicyclic condensed derivatives 6-benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones (IIa-IIf) were investigated for the prevention of ethanol-induced oxidative stress in liver and brain of mice. Administration of ethanol (0.1 mL/mice, p.o.) resulted in a drop of total thiol groups (T-SH) and non-protein thiol groups (NP-SH), and an increase in thiobarbituric acid reactive substances (TBARS) in both liver and brain tissue of mice (p<0.001). Among the compounds investigated (at a dose of 200 mg/kg, p.o.), I and IId ameliorated the peroxidative injury in these tissues effectively. Compounds IIa, IIc and IIe improved the peroxidative tissue injury only in brain. These findings suggest that certain condensed thiazolo-triazole compounds may contribute to the control of ethanol-induced oxidative stress in an organ selective manner.