STRUCTURE-ACTIVITY RELATIONSHIP INVESTIGATIONS OF 4-ANILINOPIPERIDINES H.A. Karapetyan, V.K. Jingozian, Mol. Struct. Research Center of Nat. Academy of Sciences of Armenia

The most potent narcotic analgesics, that are widely used in medicine are representatives of the 4-anilinopiperidines, the main prototype of which is Fentanyl [1-(2-ethylphenyl)-4-(N-propionylani-lino )piperidine]. On the basis of comparison of X-ray single crystal¹ and conformational energy calculations data for isomers of 2,5- and 3,5-dimethyl and 5-Me (correctly this must be named 3-Me) derivatives of Fentanyl with their individual analgesic activities, we have concluded, that the productive conformation of the molecule is that, when N(amide)-C (carbon atom of Ph-ring of aniline) bond elapsed the C(3)-C(4) bond of piperidine cycle. Subsequent exposition of productive conformation of 4-anilinopiperidines let us suppose, that 2-Me group have a negative influence on analgesic properties of the molecule and this influence is minimum when 2-Me group has an axial orientation relative to piperidine ring.

¹Karapetyan H.A., Struchkov Yu,T., Timofeeva T.V., Martirossian V.H., Vartanian R.S., Vartanian S.H. Structure and activity of phenaridine stereoisomers. Khimiko-Pharmatsevticheskii Zhurnal, 1989, V.23, No 5, P.565-572.