Preparation of Some Derivatives of Open-Lactam Form of Praziquantel

The lactam ring of the parent praziquantel was opened through hot alkaline hydrolysis. The resultant open lactam form of praziquantel (OLF- PZQ) has been subjected to various functionalization and interconversions of the amino and carboxylic acid (-NH/-COOH) groups.The methods of synthesis, and the mechanism for some selected reactions are given and discussed. Representatives of the different classes of compounds were selected and tested for their antischistosomal activity against S. mansoni in albino mice. The results indicated that these compounds were more effective on worms reduction than praziquantel. It can be seen that, compound (VIII) has six folds the antischistosomal activity of praziquantel. All the compounds have been found to possess anticestodal activity when tested against R- tetragona in Bovans type chicks, ranged from 14 to 100%, in a dose of 20 mg/kg body weight given twice in 72 hours. No clear toxicity was observed for all the tested compounds. In vivo biocyclization of some compounds has been investigated,No praziquantel or its hydroxy metabolites were detected.