Lead optimization Pharmacophore definition and 3 D searches

The most common pharmacophore building concepts based on either 3D structure of the target or ligand information are discussed together with the application of such models as queries for 3D database search. An overview of the key techniques available on the market is given and differences with respect to algorithms used and performance obtained are highlighted. Pharmacophore modelling and 3D database search are shown to be successful tools for enriching screening experiments aimed at the discovery of novel bio-active compounds.:

[1]  John H. Van Drie,et al.  Pharmacophore Discovery - Lessons Learned , 2003 .

[2]  Hugo Kubinyi,et al.  3D QSAR in drug design : theory, methods and applications , 2000 .

[3]  Thierry Langer,et al.  LigandScout: 3-D Pharmacophores Derived from Protein-Bound Ligands and Their Use as Virtual Screening Filters , 2005, J. Chem. Inf. Model..

[4]  Thierry Langer,et al.  Chemical feature-based pharmacophores and virtual library screening for discovery of new leads. , 2003, Current opinion in drug discovery & development.

[5]  Andrew R. Leach,et al.  A comparison of the pharmacophore identification programs: Catalyst, DISCO and GASP , 2002, J. Comput. Aided Mol. Des..

[6]  Yvonne C. Martin,et al.  A fast new approach to pharmacophore mapping and its application to dopaminergic and benzodiazepine agonists , 1993, J. Comput. Aided Mol. Des..

[7]  H. Kubinyi,et al.  3D QSAR in drug design. , 2002 .

[8]  Tudor I. Oprea.  Current trends in lead discovery: Are we looking for the appropriate properties? , 2002, J. Comput. Aided Mol. Des..

[9]  A. Hopfinger.  Computer-assisted drug design. , 1985, Journal of medicinal chemistry.

[10]  Hans-Joachim Böhm,et al.  The computer program LUDI: A new method for the de novo design of enzyme inhibitors , 1992, J. Comput. Aided Mol. Des..

[11]  Y. Kurogi,et al.  Pharmacophore modeling and three-dimensional database searching for drug design using catalyst. , 2001, Current medicinal chemistry.

[12]  T. N. Bhat,et al.  The Protein Data Bank , 2000, Nucleic Acids Res..