Kevser Erol

Synthesis of some thiazolyl-pyrazoline derivatives and preliminary investigation of their hypotensive activity

Some 1-(4-arylthiazol-2-yl)-3,5-diaryl-2-pyrazoline derivatives were synthesized by reacting 1-thiocarbamoyl-3,5-diaryl-2-pyrazoline derivatives with phenacetylbromide in ethanol. The structural elucidation of the compounds were performed by IR, 1H-NMR and Mass spectral data and elemental analyses. The hypotensive activities of 13 compounds were evaluated by using the tail-cuff method. All examined compounds showed appreciable hypotensive activities. Clonidine was used as reference substance in the pharmacological evaluation.

Synthesis and analgesic activity of some triazoles and triazolothiadiazines

The synthesis of some triazoles and triazolothiadiazines starting from (5,6,7,8-tetrahydronaphthalen-2-yl)oxyacetic acid is described. The chemical structure of the compounds were elucidated by analytical, IR, 1H NMR and mass spectral studies. Some of the newly synthesized compounds were tested for analgesic activity and compounds 5b, 5c, and 5d exhibited promising analgesic activity.

Synthesis of some triazolyl-antipyrine derivatives and investigation of analgesic activity.

The synthesis of some triazolyl-antipyrine derivatives starting from 4-chloroacetamidoantipyrine and 3-(aryloxyalkyl)-4-ethyl/phenyl-5-mercapto-1,2,4-triazoles is described. The chemical structures of the compounds were elucidated by IR, 1H-NMR and mass spectral studies. These compounds were tested for analgesic activity.

New pyrazoline bearing 4(3H)-quinazolinone inhibitors of monoamine oxidase : Synthesis, biological evaluation, and structural determinants of MAO-A and MAO-B selectivity

A new series of pyrazoline derivatives were prepared starting from a quinazolinone ring and evaluated for antidepressant, anxiogenic and MAO-A and -B inhibitory activities by in vivo and in vitro tests, respectively. Most of the synthesized compounds showed high activity against both the MAO-A (compounds 4a-4h, 4j-4n, and 5g-5l) and the MAO-B (compounds 4i and 5a-5f) isoforms. However, none of the novel compounds showed antidepressant activity except for 4b. The reason for such biological properties was investigated by computational methods using recently published crystallographic models of MAO-A and MAO-B. The differences in the intermolecular hydrophobic and H-bonding of ligands to the active site of each MAO isoform were correlated to their biological data. Compounds 4i, 4k, 5e, 5i, and 5l were chosen for their ability to reversibly inhibit MAO-B and MAO-A and the availability of experimental inhibition data. Observation of the docked positions of these ligands revealed interactions with many residues previously reported to have an effect on the inhibition of the enzyme. Among the pyrazoline derivatives, it appears that the binding interactions for this class of compounds are mostly hydrophobic. All have potential edge-to-face hydrophobic interactions with F343, as well as pi-pi stacking with Y398 and other hydrophobic interactions with L171. Strong hydrophobic and H-bonding interactions in the MAO recognition of 4i could be the reason why this compound shows selectivity toward the MAO-B isoform. The very high MAO-B selectivity for 4i can be also explained in terms of the distance between the FAD and the compound, which was greater in the complex of MAO-A-4i as compared to the corresponding MAO-B complex.

Synthesis and in vitro calcium antagonist activity of 4-aryl-7,7-dimethyl/1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione derivatives

In this study, a series of 4-aryl-7,7-dimethyl and 1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones (1-25) were synthesized by condensing urea or N-methylurea with 5,5-dimethyl-1,3-cyclohexanedione and appropriate aromatic aldehydes according to the Biginelli reaction. The structures of the compounds were confirmed by spectral data and elementary analysis. The calcium antagonist activity of the compounds was tested in vitro on isolated rat ileum and lamb carotid artery. Compounds 16 and 19 were the most active derivatives on isolated rat ileum compared with the standard nicardipine. On isolated aortic strips of lamb the calcium antagonist activity of compound 16 (maximum relaxant effect: 38.83+/-5.84%) was found as high as that of nicardipine (maximum relaxant effect: 35.50+/-4.16%) used as a reference drug.

Some Pyridazinone and Phthalazinone Derivatives and Their Vasodilator Activities

In this study, 6-[(4-arylidene-2-phenyl-5-oxoimidazolin-1-yl)phenyl]-4,5-dihydro-3(2H)-pyridazinone and 4-[(4-arylidene-2-phenyl-5-oxoimidazolin-1-yl)phenyl]-1(2H)-phthalazinone derivatives were synthesized by reacting 6-(4-aminophenyl)-4,5-dihydro-3(2H)-pyridazinone or 4-(4-aminophenyl)-1(2H)-phthalazinone compound with different 4-arylidene-2-phenyl-5(4H)-oxazolone derivatives. The vasodilator activities of the compounds were examined bothin vitro andin vivo. Some pyridazinone derivatives showed appreciable activity.

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.

Effects of sertraline on behavioral alterations caused by environmental enrichment and social isolation

Environmental conditions are known to play a critical role in the pathogenesis of affective disorders. In this study, the effects of sertraline, a selective serotonin (5-HT) reuptake inhibitor, on anxiety- and depression-like behaviors were investigated in rats reared in different housing conditions. Wistar rats of both sexes were divided into three groups according to their rearing conditions (Enriched = EC, Isolated = IC and Standard = SC), after weaning at postnatal day 21. While animals in control conditions were housed as a group of 4 rats in regular size plexiglass cages, social isolation groups were housed individually in metal cages. Animals in enriched conditions were housed as a group of 12 rats in specially designed cages equipped with different stimulating objects. Six weeks later, activitymeter, elevated plus maze, rotarod, grip, forced swimming and sucrose preference tests were applied to all animals and all of the tests were repeated after i.p. injection of sertraline (10 mg/kg/day) for 7 days. Environmental enrichment reduced the stereotypic behavior, improved the motor coordination and facilitated the learning skills in animals. However, housing conditions affected depression-like parameters, but not anxiety-like parameters. Sertraline treatment reduced the depression-like effect in EC and SC, but not in IC. It decreased anxiety-like behavior in IC while increased in EC. Socially isolated animals preferentially consumed more sucrose and water than the other groups, and interestingly, these differences became more significant following sertraline treatment. These results show that the responses of animals to anti-depressive drugs could be differentially affected by the behavioral consequences of the diverse housing conditions. Thus, to improve the treatment of depression; behavioral consequences of diverse housing conditions should be taken into consideration.

Synthesis and anticonvulsant activity of some ω-(1H-1-imidazolyl)-N-phenylalkanoic acid amide derivatives

In this study, 15 omega-(1H-imidazol-1-yl)-N-phenylacetamide, propionamide and butyramide derivatives having methoxyl, methyl, nitro and chloro in ortho position of N-phenyl ring or without any substituent have been realized by two-step synthesis. Their anticonvulsant activity was determined against seizures induced by maximal electroshock (MES). The most active compound in the series was 2-(1H-imidazol-1-yl)-N-(o-chlorophenyl)acetamide.

Synthesis and antinociceptive activity of (2-benzazolon-3-yl)propionamide derivatives.

The syntheses of (2‐benzothiazolinon‐3‐yl)propionamide and (2‐benzoxazolinon‐3‐yl)propionamide derivatives are reported. The structures of these compounds are elucidated by their IR and 1H‐NMR spectral data, as well as by elemental analysis. The compounds were tested for antinociceptive activity by hot plate, tail flick, tail clip, and modified Koster tests. Compounds 6b and 7d were found to be the most promising compounds among the substances investigated.