Search

The purpose of the study was to investigate the in vivo metabolic pathway of 3-oxo-5-benzylidene-6-methyl-(4H)-2-(benzoylmethyl)pyridazine (substrate) in rats. Firstly its potential metabolites, i.e. N-dealkylation, ring scission of pyridazine and aromatic hydroxylation products, were synthesized and then the substrate was given orally (100 mg/kg) to male or female Wistar rats at a dose of 100 mg/kg to body weight. Blood samples were collected at 0, 1, 2, 4, 6 and 8 hours after administration of substrate and blood was centrifuged to obtain serum. The substrate and its potential metabolites were separated using a gradient HPLC method on a reverse phase system. This study revealed that 3-oxo-5-benzylidene-6-methyl-(4H)-2-(benzoylmethyl)pyridazine was not metabolized to the proposed metabolites and was present unchanged in the serum.

In this study, ten 2-acetylnaphthalene derivatives with a dioxolane structure were synthesized and screened for their anticonvulsant activities. Dioxolane derivatives were prepared by the reaction with appropriate ethanone, glycol and p-toluensulphonic acid. The structures of the compounds were elucidated by IR, 1H-NMR and elemental analysis. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES) test and subcutaneous metrazol (ScMet.) test. The rotarod toxicity test was used for the assessment of neurological deficits. According to the activity studies compound 6 was found neurotoxic, compounds, 1, 4, 5, 7-9 were found protective against MES and 7-10 were found protective against ScMet. Compounds 2 and 3 were found inactive.

Thirteen 3-acetyl-4-aryl-5-oxo-2,7,7-trimethyl-1,4,5,6,7,8- hexahydroquinoline derivatives (5a-m), one of which was synthesized before, have been prepared. The structures of the products 5b-m were characterized by IR,1H-NMR and elemental analysis. The calcium antagonistic activity of these compounds was studied in rabbit taenia coli precontracted with 1 mmol/l Ca+2.

Fourty-three new benzoxazolinone derivatives having a piperazinomethyl group at the third position of the ring were synthesized by using appropriate benzoxazolinones and 4-substituted piperazines via a Mannich reaction. The structures of the compounds were elucidated by spectral data and microanalyses. Analgesic activities were evaluated by a modified Koster test. All compounds, except 7, 14, 21, 32, and 41, showed analgesic activity higher than that of acetylsalicylic acid. The compounds were also screened for their anti-inflammatory activity using a carrageenan paw edema test, and those exhibiting high anti-inflammatory activity were investigated for their ability to inhibit prostaglandin E2 induced paw edema. The results of anti-inflammatory testing indicated that most of the compounds were more active than indometacin. Ulcerogenic activities of the compounds were also studied and no gastrointestinal bleeding was observed at the 100 mg/kg dose level.

Some new N-arylazole acetamide derivatives have been prepared by the reaction of alpha-bromo-N-arylacetamide with imidazole, pyrazole and 1,2,4-triazole. The structures of these compounds have been confirmed by UV, IR, 1H-NMR and elementary analysis. Their anticonvulsant activities were determined by maximal electroshock (MES) and subcutaneous metrazol (Scmet) tests. Most of the compounds showed anticonvulsant activity with significantly low neurotoxicity according to Phase I tests. Compound 6 carrying alpha-naphthyl and 1,2,4-triazole was found active in the MES test with ED50 = 64.9 mg/kg and TD50 = 221.0 mg/kg but it was not active in corneally stimulated rats. Antibacterial and antifungal activities of the compounds were determined against S. aureus, E. coli, P. aeruginosa, C. albicans, C. parapsilosis, C. pseudotropicalis and C. stellatoidea by using the microdilution broth method. Compounds 8 and 10 showed significant activity (MIC < 32 micrograms/ml) against various Candida species.

The synthesis of new N,N-disubstituted carbamodithioic acid 2-oxo-2-(diphenylamino) ethyl esters is reported. The structures of these compounds are supported by their UV, IR and 1H-NMR spectra, as well as by elemental analysis. The new compounds were tested for their anticholinergic activities.

The synthesis of new 3-aroylmethyl-2H-1,3-benzoxazinedione derivatives is reported. The structure of these products are supported by their UV, IR and 1H-NMR spectra, as well as by elemental analysis. The new compounds were tested for their anticholinergic and antihistaminic activities.