Scaffold Hopping in De Novo Design. Ligand Generation in the Absence of Receptor Information
- 25 December 2003
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 47 (3) , 493-496
- https://doi.org/10.1021/jm034222u
Abstract
We report here the de novo generation of chemotypes and scaffolds for the estrogen receptor, without use of the receptor structure in the assembly phase. Through use of ligand superpositions or a single bound conformation of a known active, a pseudoreceptor can be generated as a design envelope, within which novel structures are readily assembled. Many of these structures have high similarity to known chemotypes. Scaffold hopping is readily achieved within this pseudoreceptor, indicating the advantages of such an approach in discovery research.Keywords
This publication has 19 references indexed in Scilit:
- Computer-aided design of a factor Xa inhibitor by using MCSS functionality maps and a CAVEAT linker searchJournal of Molecular Graphics and Modelling, 2003
- 3D QSAR studies of the interaction between β-tubulin and microtubule stabilizing antimitotic agents (MSAA). A combined pharmacophore generation and pseudoreceptor modeling approach applied to taxanes and epothilonesIl Farmaco, 2003
- Advances in the Science of Estrogen Receptor ModulationCurrent Medicinal Chemistry, 2003
- A validation study on the practical use of automated de novo design.Journal of Computer-Aided Molecular Design, 2002
- De novo ligand design with explicit water molecules: an application to bacterial neuraminidaseJournal of Computer-Aided Molecular Design, 2002
- Distinct Effects on the Conformation of Estrogen Receptor α and β by Both the Antiestrogens ICI 164,384 and ICI 182,780 Leading to Opposite Effects on Receptor StabilityBiochemical and Biophysical Research Communications, 1999
- Cyclic HIV protease inhibitors capable of displacing the active site structural water moleculeDrug Discovery Today, 1997
- Three-dimensional hydrogen-bond geometry and probability information from a crystal surveyJournal of Computer-Aided Molecular Design, 1996
- PRO_LIGAND: An Approach to de Novo Molecular Design. 2. Design of Novel Molecules from Molecular Field Analysis (MFA) Models and PharmacophoresJournal of Medicinal Chemistry, 1994
- Rational design of potent sialidase-based inhibitors of influenza virus replicationNature, 1993