New adamantane derivatives containing monoterpene fragments in their structure and investigation of their antipox activity

Since, WHO declared eradication of natural smallpox in 1980, Independent Advisory Group on Public Health Implications of Synthetic Biology Technology Related to Smallpox report to the WHO Director-General noted the need to continue developing new low molecular weight agents against variola virus because of a number of reasons, such as discounted vaccination, possibility of smallpox spreading from permafrost solid, bioterrorism, potential danger of other orthopoxviruses circulating in animal population.

Despite a number of adamantane derivatives is known to demonstrate antiviral activity, only few adamantane derivatives showed activity against vaccinia virus. From the other hand, monoterpene derivatives demonstrate various biological activities, in particular some camphor derivatives were found being active against vaccinia virus. To find new agents to be active against orthopoxviruses we synthesized a different adamantane derivatives containing monoterpene fragments in their structure.

For this purpose, a number of monoterpene amines was obtained starting from corresponding alcohols and ketones. Their reaction with 1- or 2-adamantane carboxylic acid chlorides led to amides. For a number of them antipox activity against vaccinia virus was demonstrated, with SI being from 5 to 1123. A most active amides were investigated against cowpox virus and ectromelia virus, with SI being from 30 to 406 and from 39 to 707 respectively.

A number of ureas and thioureas was obtained starting from isocyanates and isothiocyanates containing 1- and 2-substituted adamantane fragments and corresponding monoterpene amines as well. The antipox activity of this new adamantane derivatives hasn’t been investigated.