Classpharmer and the quest for privileged substructures


Dora Schnur, Computer-Assisted Drug Design, Bristol-Myers Squibb, Pharmaceutical Research Institute, P.O. Box 5400, Princeton, NJ 08543-5400 and Mark A. Hermsmeier, New Leads Chemistry, Bristol-Myers Squibb, P.O. Box 4000, Princeton, NJ 08543.
With the onslaught of data that has arisen from solving the human genome, creation of libraries and screening decks that are directed toward families of receptors such as GPCR’s, kinases, nuclear hormones, etc. has replaced generation of libraries and screening decks based primarily on diversity. Although diversity-based design still plays a role, particularly for orphan receptors and for receptors with no known small molecule ligands, more knowledge based approaches are required for target class design. A standard approach involves the use of privileged substructures. These “target class active” fragments or substructures may be found by various methods. This presentation focuses on the use of Classpharmer(TM) to find such substructures for target class compound sets from the MDDR as derived from Schuffenhauer,Jacoby, et al: “An Ontology for Pharmaceutical Ligands….”, JCICS 2002, 42, 947-955. It also examines the validity of the concept of "privileged substructure".