Structure-activity relationships investigation in a mixed series of cannabinoids. An electronic-topological approach.

Abstract

Structure-activity relationships (SAR) studies were performed for a series of heterocyclic cannabinoids by using the Electronic-Topological Method (ETM). Biological activities of the compounds possessing different skeletons were measured on cannabinoid receptor binding affinity. Molecular fragments being specific for active compounds only ('activity features') were revealed. In a similar way, "breaks of activity" (i.e. molecular fragments that are typical of inactive compounds and cannot be a part of an active compound) were calculated by applying the ETM. Requirements necessary for a compound to be active were formulated; they resulted from detailed analysis of all compounds under study. For better understanding, appropriate examples of the requirements violation that cause a decrease or loss of the activity in view were found.