Synthesis and pharmacological activities of novel 1-alkyl-4-aryl-6-hydroxyperhydro-1,4-diazepine-2,3-diones

The present work involves the synthesis of 1-alkyl-4-aryl-6- hydroxyperhydro-1,4-diazepine-2,3-diones through the reaction of epichlorohydrin with some selected arylamine followed by the reaction of the formed intermediates with the corresponding -cyclohexyl, alkyl, or aralkyl amines. The resulting N,N disubstituted-1,3-diamino-2-propanols were cyclized with diethyl oxalate to afford the target compounds. The structures of the obtained compounds were verified by spectral and elemental methods of microanalysis. Fifteen of the final compounds were subjected to preliminary pharmacological screening as regards their anticonvulsant activity. In addition, evaluation of the hypotensive activity of twenty two compounds was performed. Most of the tested compounds gave 100% protection against pentylenetetrazole-induced convulsions with a faster onset of action [15 min] than diazepam [30 min]. On the other hand, most of the tested compounds gave mild to ~ 50-80% reduction in blood pressure in comparison to that of propranolol. Moreover, the cytotoxic activity of twenty eight final compounds was determined and only three of them elicited mild cytotoxic effects. Also, the median lethal dose [LD50] of four target representative compounds was determined and was found to range between 10-20 mg/kg [i.p.]

Synthesis of certin 2-aroylindole derivatives of poential analgesic, anti-inflammatory and antopyretic activities

In the present study, a series of 2-aroylindole derivatives were synthesized by phase transfer catalysis [PTC] and were characterized by IR, 1H-NMR, Mass spectral and Elemental analysis. Indole derivatives 6a-g, 7a-f 8a-f and 9a-13a were tested for analgesic activity using hot-plate test. Compounds 7b and 8b were tested far antipyretic and anti-inflammatory activity using yeast induced hyperthermia and paw edema in rats. Analgesic activity was shown when indole nucleus was substituted at position 2 and 3 by phenyl and [p-halo] benzoyl moieties respectively, where highest activity was recognised in compounds 7b and 8b. Both compounds also exhibited faster, more effective and prolonged reduction in hyperthermia and edema induced in rats compared with indomethacin. Compounds 7b and 8b were also tested for ulcerogenic activity in mice, where a lower ulcerogenie effect was observed compared with indomethacin at all tested dose levels

Synthesis of trigonelline and nicotinamide linked prodrugs of 5-aminosalicylic acid [5-ASA] with analgesic and anti-inflammatory effects

3-N-[4'-Hydroxy-3'-substituted phenyl] carbamoyl-1-methylpyridinium iodides [compds. 5b-j] and 3-carbamoyl-1-[N-[4'-hydroxy- 3'-substituted phenyl] carbamoyl] methyl pyridinium chlorides [compds. 7a-j] were synthesised and some of them were tested for their analgesic and anti-inflammatory activities by hot plate test and carageenin-induced hind paw edema model, respectively. Compound 5b revealed the most potent analgesic and anti-inflammatory activities in comparison to sulfasalazine [SASP] and 5-ASA. In addition, ulcerogenicity, LD [50], in-vivo and in vitro cleavage and pH stability of compound 5b were also determined

New 1, 4-disustituted-6-hydroxyperhydro-1,4-diazepine- 2,3-dione derivatives

A series of 1,4-disubstituted-6-hydroxyperhydro-1,4-diazepine-2,3-diones were designed and synthesized through the reaction of epichlorohydrin with an excess of the appropriate primary amine. The resulting secondary diamine derivatives were allowed to react with diethyl oxalate to afford the target compounds in good yields. Structures of the target compounds were verified on the basis of spectral and elemental methods of analysis. Twelve new derivatives were subjected to preliminary pharmacological screening regarding their CNS depressant activity such as sedative, hypnotic, anticonvulsant as well as muscle relaxant activities, in addition to evaluation of the hypotensive activity of some representative compounds. Most of the tested compounds gave high percentage reduction in spontaneous locomotor activity [SLA] compared with diazepam. Concerning the rota-rod coordination test, mice cannot remain on the rod more than 20 seconds in comparison with the reference drug used indicating a good muscle relaxant activity of the test compounds. Moreover, these compounds gave 100% protection against pentylenetetrazole-induced convulsions with a rapid onset of action. On the other hand, most of the test compounds gave mild to comparable reduction in blood pressure in comparison to that produced by using propranolol. Moreover, the acute toxicity [LD50] test was carried out for only one representative compound

Role of urethral wall components in the continence mechanism

An experimental model is used to test the role of the components of the urethral wall and its elasticity in the continence mechanism. The model consists of [1] a modified plastic syringe with three openings; one on each end and the third on its upper surface [2] a condom, a double condom and a double condom with K - Y jelly in between acting as a urethra