A Density Functional Theory Study Of The Relationships Between Electronic Structure And Metabotropic Glutamate Receptor Subtype 5 Affinity Of 2- Amino- And 2-Halothiazole Derivatives

Abstract

We carried out an investigation and analysis of the relationships between the electronic structure and the metabotropic glutamate receptor subtype 5 affinity for a series of 2-amino- and 2-halothiazole derivatives using a model-based method. The electronic structure of all the molecules was calculated within the Density Functional Theory at the B3LYP/6-31g(d,p) level with full geometry optimization. Linear multiple regression analysis techniques were employed to find the best relationship between receptor binding affinity and local atomic reactivity indices belonging to a common skeleton. The variation of the receptor binding affinity is related to the variation of a set of three local atomic reactivity indices. The corresponding partial interaction pharmacophore is construed. The interaction with the receptor seems to be orbital-controlled. This is another example showing the absolute necessity of using formal quantum-chemical methods to study the microscopic basis of drug action.