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

11 ELECTRONIC-TOPOLOGICAL INVESTIGATION OF THE STRUCTURE - ACETYLCHOLINESTERASE INHIBITOR ACTIVITY RELATIONSHIP IN THE SERIES OF N- BENZYLPIPERIDINE DERIVATIVES (PhD Thesis) Murat SARAÇO?LU GAZİ UNIVERSITY INSTITUTE OF SCIENCE AND TECHNOLOGY May 2001 ABSTRACT The "structure - acetylcholinesterase (AChE) inhibitor activity" relationship study is performed for four series of N-benzylpiperidine derivatives by the Electronic-Topological Method (ETM) that is a structural approach designed for the structure-property relationship studies. Biological activities of the compounds belonging to four different series have been measured on mouse, human, rat and Torpedo californica AChE. Molecular fragments that are only specific for active compounds ('farmakofor features') are 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 be a part of an active compound) are calculated by applying the ETM. Requirements necessary for a compound to be active are formulated; they are the result of a detailed analysis of all compounds under study. A comparative study of the activity features found relative to three different AChE is also performed. Science code : 404.04.01 Key words : Reversible AChE Inhibitors, 3D QSAR, Electronic-Topological Method, Alzheimer Disease Pages number: 165 Advisor : Prof.Dr. Melike KABASAKALO?LU Prof.Dr. Anatoli DİMOGLO