Novel tetrahydropyrimidine–adamantane hybrids as anti-inflammatory agents: synthesis, structure and biological evaluation

A series of novel (3-((3s,5s,7s)-adamantan-1-yl)-1-alkyl/aralkyl/aryl-1,2,3,4-tetrahydroyrimidin-5-yl)(aryl)methanones (5a–j) has been synthesized by the reaction of 1-aryl-3-(alkyl/aralkyl/aryl)aminoprop-2-en-1-ones 3a–j, 1-adamantanamine 4 and formaldehyde under thermal conditions. The structures of the products (5a–j) have been established with the help of spectral and analytical data. The stereochemistry of the products was established by X-ray crystallographic studies of a representative product (3-((3s,5s,7s)-adamantan-1-yl)-1-methyl-1,2,3,4-tetrahydropyrimidin-5-yl)(4-chlorophenyl) methanone (5g) of the series. The target adamantane–tetrahydropyrimidine hybrids 5a–j were evaluated for their anti-inflammatory activities as a result of which compounds 5e (R=C6H5CH2, Ar=C6H5), 5i (R=CH3, Ar=4-CH3C6H4), 5j (R=C6H5CH2, Ar=4-CH3C6H4) and 5g (R=CH3, Ar=4-ClC6H4) were found to exhibit excellent and promising anti-inflammatory activities.