SYNTHESIS AND PHARMACOLOGICAL ACTIVITIES OF NOVEL 1-ALKYL-4-ARYL-6-HYDROXYPERHYDRO1,4-DIAZEPINE-2,3-DIONES

Abdel-Alim, A. M.; Hussein, M. A.; El-Shorbagi, A. A.; AbuElMagd, A. A.; El-Menshawi, B. S.

doi:10.21608/bfsa.2006.65199

SYNTHESIS AND PHARMACOLOGICAL ACTIVITIES OF NOVEL 1-ALKYL-4-ARYL-6-HYDROXYPERHYDRO1,4-DIAZEPINE-2,3-DIONES

Document Type : Original Article

Authors

¹ Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut-71526, Egypt

² Department of Pharmacognosy, National Research Centre, Dokki, Giza, Egypt

10.21608/bfsa.2006.65199

Abstract

The present work involves the synthesis of 1-alkyl-4-aryl-6hydroxyperhydro-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.).