Mustafa Fethi Sahin

Synthesis and antinociceptive activity of 6-substituted-3-pyridazinone derivatives.

A series of 3-pyridazinones carrying morpholino, arylpiperidino and arylpiperazino moiety in the position 6 IIa-g were synthesized and evaluated for antinociceptive activity. In the modified Koster test in mice 4-(4-fluorophenyl) piperazine, IIf, was found the most active compound. All the compounds except IId were more active than aspirin in the antinociceptive activity test.

Synthesis and antinociceptive activity of [(2-oxobenzothiazolin-3-yl)methyl]-4-alkyl/aryl-1,2,4-triazoline-5-thiones

The synthesis and pharmacological evaluation of new [(2‐oxobenzothiazolin‐3‐yl)‐methyl]‐ 4‐alkyl/aryl‐1,2,4‐triazoline‐5‐thiones are reported. All compounds were screened for analgesic and antiinflammatory activities by using the AcOH induced‐stretching test, the hot plate test, the tail clip test, and the tail flick test. All of the title compounds showed more potent activity than the standard compound aspirin in the AcOH induced‐stretching test. In the hot plate test [(2‐oxobenzothiazolin‐3‐yl)methyl]‐4‐phenethyl‐1,2,4‐triazoline‐5‐thione 5j were revealed to be two‐fold more potent in antinociceptive activity than novalgine. However, in the tail flick and tail clip test none of the compounds showed an antinociceptive activity as high as that of novalgine. On the basis of available data the structure‐activity relationship in the [(2‐oxobenzothiazolin‐3‐yl)methyl]‐4‐alkyl/aryl‐1,2,4‐triazoline‐5‐thiones was also discussed.

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.

Synthesis and antinociceptive activity of (5-chloro-2-benzothiazolinon-3-yl)acetamide derivatives.

The synthesis of (5‐chloro‐2‐benzothiazolinon‐3‐yl)acetamide derivatives is reported. The structure of these compounds is supported by their IR and 1H‐NMR spectra. The compounds were tested for antinociceptive activity.

Synthesis and antimicrobial, acetylcholinesterase and butyrylcholinesterase inhibitory activities of novel ester and hydrazide derivatives of 3(2H)-pyridazinone

In the current study, some novel ethyl 6- [(substituted-phenylpiperazine]-3(2H)-pyridazinone-2-yl propionate III and 6-[(substituted-phenylpiperazine]-3(2H)-pyridazinone-2-yl propionohydrazide IV derivatives were synthesized as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The structures of these new pyridazinone derivatives were confirmed by their IR, 1H-NMR spectra and elementary analysis. 6-Substituted-3(2H)-pyridazinone-2-yl propionate IIIa-e derivatives showed significant inhibitory activity against AChE and BChE. 6-[4-(3-Trifluoromethylphenyl)piperazine]-3(2H)-pyridazinone-2-yl propionate IIIe has been found to be the most active compound in terms of inhibition of either AChE or BChE. Compound IIIe exhibited inhibitory activity close to that of galantamine (CAS 357-70-0) and did not show any selectivity between the two enzymes. Also the antimicrobial activities of III and IV derivatives have been evaluated. All III and IV derivatives exhibited poor antibacterial activities but moderate antifungal activities.

Synthesis and analgesic and anti-inflammatory activity of ethyl (6-substituted-3 (2H)-pyridazinone-2-yl)acetate derivatives.

A number of 6-substituted-3(2H)-pyridazinones and the corresponding methyl (6-substituted-3(2H)-pyridazinone-2-yl)acetate derivatives carrying the arylpiperazinyl structure present in potent antinociceptive agents reported in the literature were synthesized. As part of a programme a series of diverse arylpiperazine derivatives of ethyl (6-substituted-3(2H)-pyridazinone-2-yl)acetate 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. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect compared with reference non-steroidal anti-inflammatory drugs (NSAIDs). On the basis of available data, the structure-activity relationship in the series of ethyl (6-substituted-3(2H)-pyridazinone-2-yl)acetate derivatives was also discussed. When compared to parent 6-substituted-3(2H)-pyridazinones, the new ester derivatives, for example ethyl (6-4-[(2-fluoro)phenyl]piperazine-3(2H)-pyridazinone-2-yl)acetate exhibited better analgesic and anti-inflammatory activity and a lower ulcerogenic effect.

The in vitro hepatic microsomal metabolism of methyl 2-(2(3H)-benzoxazolone-3-yl)acetate in rats.

The in vitro hepatic microsomal metabolism of methyl 2-(2(3H)-benzoxazolone-3-yl)acetate (I) was studied using hepatic washed rat microsomal preparations fortified with NADPH. The substrate (I) and its potential hydrolytic metabolite 2-(2(3H)-benzoxazolone-3-yl)acetic acid (II) and 2(3H)-benzoxazolone (III), a potential dealkylation metabolite, were separated using a reverse phase HPLC system which consisted of a C18 column and a mobile phase of acetonitrile: 0.02 M phosphate buffer (30:70, final pH 7) at a flow rate of 1 ml/min with UV detection at 254 nm. The substrate (I) was incubated with rat microsomal preparations, extracted into DCM, and finally evaporated under nitrogen. The results from HPLC studies showed that (I) was metabolised to (II) and (III) by rat microsomes in the presence of NADPH.