Synthesis and analgesic activity of amines combining diazaadamantane and monoterpene fragments

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 and¹³C 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.