Synthesis Of Piperazine Compounds And Their Activities In Antiallergy

Allergy is a kind of excessive immune reaction. Allergic diseases are abroad in clinic. However, the incidence of the kind of disease tends to increase recently. Among the therapies for it, H₁ receptor antagonists (antihistamines) have shown to be effective clinically in the treatment of allergies. The classical antihistamines have some side effects such as restraining the central nervous system (CNS) and lasting shortly. Although the new antihistamines have no such side effect, some of them still have other side effects such as the latent harm to the heart and vessel system. It is important to study and explore the new antihistamines that have more significant effect and less side effect.Cetirizine is an kind of excellent antihistaminic drug, bearing diphenylmethylpiperazine skeleton. Recently, it was repoted that levocetirizine displayed a better pharmacological profile than the racemic mixture. Therefore, we decided to synthesize some levogyrate enantiomers of them. Nineteen levogyrate compounds were synthesized. At the same time, through investigating the antihistaminic drugs of Chlorpheniramine, we replaced pyridine ring to one phenyl ring of diphenylmethylpiperazine skeleton, two compounds which include pyridine ring were synthesized. All the compounds were identified by MS, IR, ¹H-NMR and elemental analysis.The results of the initial anti-allergic asthma and antipruritic tests showed that seventeen compounds had significant effect in asthma, the activities of WTW-08, WTW-10, WTW-13, WTW-17 and WTW-19 was equel to the activities of the positive comparison drug Chlorpheniramine, the activities of WTW-04, WTW-09, WTW-18 and WTW-20 was higher than Chlorpheniramine; fifteen compounds had significant antipruritic effect, the activities of WTW-11, WTW-15 and WTW-18 was equel to the activities of the positive comparison drag Chlorpheniramine, the activities of WTW-07 and WTW-19 was higher than Chlorpheniramine.