Electronic-topologic investigation of the structure-acetylcholinesterase inhibitor activity relationship in the series of N-benzylpiperidine derivatives

"Structure-acetylcholinesterase (AChE) inhibitor activity" relationship stu dies have been performed for three series of N-benzylpiperidine derivatives using the Electronic-Topological Method (ETM) which is a structural approa ch designed for the investigation of structure-property relationships. Biol ogical activities of the compounds belonging to three different series have been measured on mouse, human and Torpedo californica AChE. Molecular frag ments that are only specific for active compounds ("activity features") wer e found for each of these series. In a similar way, "breaks of activity" (i .e. molecular fragments that are typical of inactive compounds and cannot b e a part of an active compound) were calculated by applying the ETM. Requir ements necessary for a compound to be active are formulated; they are the r esult of a detailed analysis of all compounds under study. The analysis sho ws that any violation of these requirements for a molecule decreases consid erably or even provokes a complete loss of its activity. A comparative stud y of the activity features found relative to three different AChE has also been performed.