Conformational analysis and neuroleptic pharmacophore identification
Jan P. Tollenaere, Henri Moereels, L. A. Raymaekers · 1984
It is now widely accepted that the three-dimensional (3-D) characteristics of drug molecules are of utmost importance for a better classification of drugs into various pharmacological classes and towards a better understanding of how molecules could possibly interact with a putative receptor. The advent of routine X-ray crystallographic techniques and powerful computational approaches offer the medicinal chemist an unprecedented opportunity to describe molecules in terms of their spatial properties. Conformational analysis, however, is not an end in itself, but rather the basis for answering the question as to which 3-D features are essential for recognition by the receptor. In principle, the search for the essential 3-D features can be done by examining all energetically allowed conformations of a series of molecules supposedly acting on the same receptor, from which a common pharmacophoric pattern may emerge. This pharmacophore is then defined as the set of atoms or chemical functions in a mutually characteristic orientation, essential for recognition by and interaction with that particular receptor.