M. Fethi Sahin

Studies on some 3(2H)-pyridazinone derivatives with antinociceptive activity.

Nineteen new [6‐(4‐methoxyphenyl)‐3(2H)‐pyridazinone‐2‐yl]‐acetamide (1—10) and 3‐[6‐(4‐methoxyphenyl)‐3(2H)‐pyridazinone‐2‐yl]propanamide (11—19) derivatives have been synthesized in this study. The structures of the compounds have been elucidated by their IR and NMR spectral data and elemental analysis. Antinociceptive activity of the compounds has been investigated by modified Kosters Test in mice, using aspirin as a reference. All the compounds (at 100 mg/kg dose) except >1 and 9 have been found more potent than aspirin. Compound 6 in the group of acetamide derivatives and compound 15 in the group of propanamides exhibited the highest antinociceptive activity. In addition, the propanamides have generally been found more potent than acetamides. In addition to these studies, the quantitative relation‐ships between some structural parameters (such as log P, parachor, molar refractivity, and molecular connectivity indices) and antinociceptive activity of the compounds have been investigated. Statistical regression analysis has shown a close relationship to exist between the first‐order molecular connectivity index (1 χ) and the antinociceptive activity.

Synthesis, Analgesic, and Anti-Inflammatory Activities of [6-(3,5-Dimethyl-4-Chloropyrazole-1-yl)-3(2H)-Pyridazinon-2-yl]Acetamides

A series of structurally diverse amide derivatives of [6-(3,5-dimethyl-4-chloro-pyrazole-1-yl)-3(2H)-pyridazinone-2-yl]acetic acid were prepared and tested for their in vivo analgesic and anti-inflammatory activity by using p-benzoquinone-induced writhing test and carrageenan-induced hind paw edema model, respectively. The analgesic and anti-inflammatory activity of the compounds, 7c, 7d and 7k were found to be equipotent to aspirin (as an analgesic) and indometacin (as an anti-inflammatory drug), respectively. The other amide derivatives generally resulted in lower activity on comparision with reference compounds.

Synthesis and anticonvulsant activity of some (2/4-substituted)benzaldehyde (2-oxobenzothiazolin-3-yl)acetohydrazones

Fifteen new (2/4-substituted)benzaldehyde (2-oxobenzothiazolin-3-yl)acetohydrazones were synthesized and their structures were elucidated by NMR and elemental analysis. Their anticonvulsant activity was tested by a pentylenetetrazole induced seizure test. Compounds 4e and 4h were found to be the most promising among the others.

Synthesis of some new 2,6-disubstituted-3(2H)-pyridazinone derivatives and investigation of their analgesic, anti-inflammatory and antimicrobial activities

In this study, 12 new 3(2H)-pyridazinone derivatives carrying 4-substituted phenylpiperazinylethyl moiety on lactam nitrogen were synthesized and their chemical structures were confirmed by 1H-NMR, mass, and elemental analysis. Analgesic and anti-inflammatory activities of the synthesized compounds were evaluated in mice. Among the synthesized compounds, compound 9c showed the best analgesic and anti-inflammatory activities without causing any gastric effect in stomachs of tested animals. In addition, the synthesized compounds were screened for their antibacterial and antifungal activities against some pathogenic strains.

Synthesis and antinociceptive activity of some 3-substituted benzothiazolone derivatives

Thirteen 3-substituted benzothiazolone derivatives have been synthesized. Their chemical structures have been elucidated by IR and NMR spectral data and by elemental analyses. Among these compounds, 1-¿3-[2(3H)-benzothiazolon-3-yl[propanoyl]morpholine (5b); 1-¿3-[2(3H)-benzothiazolon-3-yl[propanoyl]-4-benzylpiperidine++ + (5c); 1-¿3-[2(3H)-benzothiazolon-3-yl[-propanoyl]-4-phenylpiperazine (5d); 3-[3-(4-benzylpiperidine-1-yl)propyl]-2(3H)-benzothiazolone (5k); 3-[3-(4-benzylpiperazine-1-yl)propyl]-2(3H)-benzothiazolone (5I); 3-[3-(4-phenylpiperazine-1-yl)propyl]-2(3H)-benzothiazolone (5m) have been found to be significantly more active than the others.

Synthesis and antinociceptive activity of (5-chloro-2(3H)-benzoxazolon-3-yl) propanamide derivatives

In this study, (5-chloro-2(3H)-benzoxazolon-3-yl)propanamide derivatives were synthesized. The chemical structures of the compounds were elucidated by their IR and1H-NMR spectral data and microanalysis. The compounds were tested for antinociceptive activity by using the tail clip, tail flick, hot plate, and writhing methods. The varying levels of antinociceptive activity of the compounds were compared with those of dipyrone and aspirin. Among these compounds, compound5e, 5g, and5h have been found to be significantly more active than the others and the standards in all the tests.

Synthesis and Analgesic Activity of 1‐(1‐Piperidinyl)methyl‐2‐(4‐substituted styryl)‐5‐chlorobenzimidazole Derivatives

Seven 1-(1-piperidinyl)methyl-2-(4-substituted styryl)-5-chlorobenzimidazole derivatives were synthesized by the reaction of 2-(p-substituted styryl)-5-chlorobenzimidazoles with formaldehyde and piperidine in methanol. Analgesic activity of the 1-(1-piperidinyl)-methyl-2-(4-substituted styryl)-5-chlorobenzimidazole derivatives was investigated by the modified Koster test in mice. No obvious relationships between analgesic activity and the nature of the substituent on the styryl group was found.