Structure-activity relationships of convulsant and anticonvulsant barbiturates: a computer-graphic-based...

A computer-graphic-based pattern-recognition study of two series of 5-ethyl-5-substituted barbiturates has been undertaken in an attempt to find a correlation between molecular conformation and convulsant and anticonvulsant activity. Studies of a first (trial) set of barbiturates related to pentobarbital revealed a region of space in which at least one low-energy conformation of the hydrocarbon side chain of each of the anticonvulsant barbiturates resides. Another region was occupied by a low-energy conformation of each of the convulsant barbiturates. These regions of space are, thus, possible pharmacophores for convulsant and anticonvulsant activity. Analysis of a second (test) set of barbiturates related to phenobarbital has shown that the activities and structures of these molecules are consistent with the above model. These pharmacophores thus provide a basis for the design of rigid, new analogues with potent convulsant or anticonvulsant activities.