Keywords
Abstract
Pathologies related or accompanied by pain and inflammation are among the most widespread. Currently, there is no analgesic and anti-inflammatory drug, which would optimally satisfy clinical efficiency and/or safety requirements. This is why search for new compounds of this group, which exceed modern analogues in their properties, is relevant and important. In the last years, in terms of search for new analgesic and anti-inflammatory drugs, azulenes derivatives, which show antiexudative and antinociceptive activity are the most interesting. The aim of the study was to research analgesic and anti-inflammatory activity of new derivatives of 1-phenoximethyl-4-(R-phenyl)-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulene. The synthesis of 1-phenoximethyl-4-(R-phenyl)-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulene derivatives was carried out. Composition and compound's structure were proven by PMR-spectra. Primary evaluation of anti-inflammatory and analgesic activity of new derivatives of 1-(phenoximethyl)4-(R-phenyl)-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulene, was conducted on «Carrageenan swelling» and «Acetic writhings» models, correspondingly using sodium diclofenac («Carrageenan swelling») and ketorolac («Acetic writhings») as comparator drugs. Studied compounds were administered intragastrically at dose of 25 mg/kg in form of water-ethanol emulsion with use of Tween-80 as emulgator. Statistic data processing was conducted by using parametric statistic methods (t-test). It’s shown, that derivatives of 1-(phenoximethyl)-4-(R-phenyl)-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulene (excluding compound 4 f (R = p-F-), are characterized by pronounced antinociceptive activity, which is close to or exceeds that of ketorolac. Most active compounds 4 а (R = Н), 4 c (R = Et) and 4 е (R = EtO) exceed the reference drug ketorolac. Thus, compounds are characterized by peripheral component of antinociceptive activity. The majority of studied compounds had not shown anti-exudative activity. Considering that the model of carrageenan swelling characterizes cyclooxigenase link of inflammation, it can be assumed that these compounds are not COX inhibitors.