Synthesis and Analgesic Activity of Amines Combining Diazaadamantane and Monoterpene Fragments

Abstract

Background: It was found earlier that compounds combining diazaadamantane and monoterpene moieties possessed promising analgesic activity along with low acute toxicity and the lack of ulcerogenic activity.

Objective: In this paper, new structural analogues of the most active compounds were synthesized and evaluated for their analgesic activity.

Methods: Their structures were confirmed by various analytical methods, such as 1H and 13C NMR, HRMS. All of them were evaluated for analgesic activity at a dose of 20 mg/kg or less using acetic acid-induced writhing test and hot plate test.

Results: Some compounds showed analgesic activity in acetic acid-induced writhing test. One of the synthesized compounds demonstrated high analgesic activity in both tests with 46% effect in acetic acid-induced writhing test and 89% effect in hot plate test. Both structural fragments of this compound did not possess any analgesic effect at a dose of 20 mg/kg.

Conclusion: Structure-activity relationships indicated that the most active compound combines fragments of (-)-myrtenal and 6-amino-5,7-dimethyl-1,3-diazaadamantane. Both parts of the molecule are important for demonstrating analgesic activity.

Keywords: Monoterpene; acetic acid-induced writhing test; adamantane; analgesic activity; azaadamantane; heterocyclic compounds; hot plate test.