Synthesis of novel 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/-nonsubstituted benzal)hydrazone derivatives and acetylcholinesterase and butyrylcholinesterase inhibitory activities in vitro.

In this study thirteen 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(substituted/nonsubstituted benzal)hydrazone V derivatives were synthesized as acetylcholinesterase and butyrylcholinesterase inhibitors. Ten of the synthesized compounds were synthesized for the first time in this study and the rest of them had been synthesized in a previous study. The structures of compounds V were elucidated by IR, 1H-NMR and MASS spectra. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChe) inhibitory activities of V derivatives were measured using Ellman's method. While some of the 6-substituted-3(2H)-pyridazinone-2-propyl-3-(substituted/-nonsubstituted benzal)hydrazone V derivatives exhibited significant AChE inhibitory activity, none of the compoundsshowed BChE inhibitory activity. Theseresults indicate that V derivatives were AChE inhibitors with AChE/ BChE selectivity.

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.

3-Chloro-6-{4-[3-(trifluoro-meth-yl)phen-yl]piperazin-1-yl}pyridazine.

The title compound, C(15)H(14)ClF(3)N(4), was synthesized from 3,6-dichloro-pyridazine and 1-[3-(trifluoro-meth-yl)phen-yl]piper-azine. The piperazine ring is flanked by 3-chloro-pyridazine and 3-trifluoro-methyl-phenyl rings and adopts a chair conformation, whereas the 3-chloro-pyridazine and 3-trifluoro-methyl-phenyl rings are planar, with maximum deviations of 0.0069 (13) and 0.0133 (14) Å, respectively. The crystal structure is stabilized by weak inter-molecular C-H⋯N hydrogen-bond inter-actions.

Synthesis and analgesic and anti-inflammatory activity of 6-phenyl/(4-methylphenyl)-3(2H)-pyridazinon-2-propionamide derivatives.

For reducing gastrointestinal toxicity associated with non-steroidal anti-inflammatory drugs (NSAIDs) a variety of 6-phenyl/(4-methylphenyl)-3(2H)-pyridazinon-2-propionamide were synthesized. The structures of these new pyridazinone derivatives were confirmed by their IR, 1H-NMR spectra and elementary analysis. All the new compounds were tested in vivo for their analgesic and anti-inflammatory activities. The analgesic activity of the test compounds was determined by phenylbenzoquinone-induced writhing assay and the anti-inflammatory activity was evaluated by the carrageenan-induced rat paw edema model. 6-Phenyl-3(2H)-pyridazinon-2-yl-[4-(4-fluorophenyl)piperazinyl] propanamide IVa-3 was the most active one among the synthesized compounds. Also this compound exhibited most potent anti-inflammatory activity. Acetylsalicylic acid and indometacin were used as reference drugs. Adverse effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect compared with the reference NSAIDs.

Synthesis and analgesic and anti-inflammatory activities 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substituted/nonsubstituted benzal)hydrazone derivatives.

In this study new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substituted benzal)hydrazone V derivatives were synthesized as analgesic and anti-inflammatory agents. The structures of compounds were elucidated by spectral and elemental analysis. Compounds Va, Vb and Vc were exhibited more potent analgesic activity than ASA. Also these derivatives demonstrated anti-inflammatory activity as well as standard compound indomethacin. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed gastric ulcerogenic effect compared with reference nonsteroidal anti-inflammatory drugs (NSAIDs). On the basis of available data, the structure-activity relationship of V derivatives was also discussed.

3-Chloro-6-[4-(2-pyrid-yl)piperazin-1-yl]pyridazine.

In the title compound, C(13)H(14)ClN(5), the piperazine ring adopts a chair conformation and the dihedral angle between the aromatic rings is 13.91 (7)°. The crystal structure is stabilized by weak inter-molecular C-H⋯N hydrogen-bond inter-actions.

Synthesis and anticonvulsant activity of 5-chloro-2(3H)-benzoxazolinone-3-acetyl-2-(o/p-substituted benzal) hydrazone derivatives.

It is well known that some hydrazone derivatives of both 2-oxobenzoxazoline and 2-oxobenzothiazoline exhibit potent anticonvulsant activity. In order to investigate the effects of structural modifications on the biological properties, 14 new hydrazones of 5-chloro-2(3H)-benzox-azolinone-3-acetyl hydrazide were synthesized. The chemical structures of the synthesized compounds were established by IR, 1H-NMR spectral analyses and elementary analyses. The anticonvulsant activities of the title compounds were tested by the penthylenetetrazole induced seizure test. 5-Chloro-2(3H)-benz-oxazolinone-3-acetyl-2-(o-methoxy-benzaldehyde)-hydrazone 4d, 5-chloro-2(3H)-benzoxazolinone-3-acetyl-2-(o-methybenzaldehyde)-hydrazone 4g, 5-chloro-2(3H)-benzoxazolinone-3-acetyl-2-(p-methylbenzaldehyde)-hydrazone 4h, 5-chloro-2(3H)-benzoxazolino-ne-3-acetyl-2-(p-nitrobenzaldehyde)-hydrazone 4m, and 5-chloro-2(3H)-benzox-azolinone-3-acetyl-2-(p-dimethylaminobenzaldehyde)-hydrazone 4n were found more active than phenytoin (CAS 57-41-0) in the tests.

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.

Synthesis of new Mannich bases of arylpyridazinones as analgesic and anti-inflammatory agents.

A series of 2-[[4-(substituted-phenyl/ benzyl)-1-piperazinyllmethyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone derivatives was prepared and examined for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR and 1H-NMR spectra and elementary analysis. Among the compounds prepared, 2-[[4-(4-fluorophenyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H)pyridazinone IVe was found to be a most promising analgesic and anti-inflammatory agent. Compound IVe showed more potent analgesic activity than acetylsalicyclic acid in the phenylbenzoquinone-induced writhing test. Also IVe showed anti-inflammatory activity comparable to that of the standard compound indometacin against the carrageenan-induced paw edema. Side effects of the compounds were examined on gastric mucosa. None of the compounds showed a gastric ulcerogenic effect compared with reference nonsteroidal anti-inflammatory drugs. On the basis of the available data, the structure-activity relationship of the series of 2-[[4-(substituted-phenyl/benzyl)-1-piperazinyl]methyl]-6-(4-methoxyphenyl)-3(2H) pyridazinones is also discussed.

Synthesis and evaluation of the analgesic and anti-inflammatory activity of new 3(2H)-pyridazinone derivatives.

A series of 6-substituted-3(2H)-pyridazinone derivatives were synthesized and evaluated for analgesic and anti-inflammatory activities. The structures of these new pyridazinone derivatives were confirmed by their IR, 1H-NMR spectra and elementary analysis. Analgesic and anti-inflammatory activities of the title compounds have been evaluated. Four of the ten tested compounds possessed significant analgesic effects in the phenylbenzoquinone-induced writhing test (PBQ test). The most active derivatives 8a, 8b, 8d, 8e were void of gastric ulcerogenic effect or acute toxicity at the maximal dose (200 mg/kg p.o.). In the carrageenan-induced paw edema model, compound 8d (6- [4- (2-fluorophenyl) piperazin-1-yl]-3(2H)-pyridazinone) showed anti-inflammatory activity similar to that of the standard drug indometacin (CAS 53-86-1). A significant dependence of the anti-inflammatory effect on the substituents was observed; The pharmacological study of these compounds confirms that modification of the chemical group at position 6 of the 3(2H)-pyridazinone ring influences analgesic and anti-inflammatory activities.

Antiviral and antimicrobial activities of new nitrobutane derivatives.

It is known that some addition products of beta-nitrostyrenes exhibit potent antimicrobial activity. In order to investigate the effects of structural modifications on the biological properties, some new Michael type addition products of beta-ethyl-beta-nitrostyrenes were synthesized. In this study, eight new 1-[(2-aminophenyl)thio]-1-phenyl-2-nitrobutane (2) derivatives were synthesized by addition of 2-aminothiophenol to the double bond of beta-ethyl-beta-nitrostyrenes (1). The chemical structures were proved by IR and 1H-NMR data and by elemental analysis. Antimicrobial activities of the synthesized compound were investigated against Escherichia coil, Pseudomonas aeruginosa, Proteus mirabilis, Enterococcus faecalis, Bacillus subtilis, Staphylococcus aureus, Candida albicans by the microdilution method. In addition, the newly synthesized compounds were studied for antiviral activities. All of them were found to be almost 100 fold more active than the standard compound aciclovir (CAS 59277-89-3).