ChemDiverse

ChemX/ChemDiverse, PharmPrint, OSPPREYS, 3D Keys, Tuplets... 

One of the most popular applications is ChemX/ChemDiverse of Chemical Design/Oxford Molecular (now Accelrys). Details of the approaches used there are included in this review by Mason et al. [3], Another example, of an in-house pharmacophore fingerprint construction, is PharmPrint by Affymax [4, 5]. 

ChemDiverse, Chemical Design Ltd., Roundway House, Cromwell Park, Chipping Norton, Oxfordshire, 0X7 5SR, UK. 

A similar approach based on pharmacophore keys is used in the ChemDiverse software [54]. Here, the key is based on three-point pharmacophores generated for seven features over 32 distances. This gives over 2 million theoretical combinations however, this number can be reduced by geometric and symmetry considerations. The key marks the presence or absence of the pharmacophores within the collection and because of its size it is normally used to represent a whole library of compounds, although in principle it can also be used to represent a single compound. 

ChemDiverse. Oxford Molecular Group, Oxford Science Park, Oxford, UK. 

ChemDiverse software (which refers to them as centres ), and this seventh feature can be used to define a special point for relative similarity/diversity studies. By default, in ChemDiverse this extra feature is... 

The ChemDiverse method uses predefined ranges for measuring the distances between the points (pharmacophoric features) distances are calculated exactly but stored using this binning scheme, with each distance represented by the bin into whose range it falls. Each pharmacophore for the 4-point method needs six distances to be characterised (to form a tetrahedron), whereas three distances are needed for each 3-point pharmacophore (triangle). All the combinations of features and distances, combined for all the evaluated conformers, are stored in a pharmacophore key . 

The relatively high conformational flexibility of many drug molecules requires that an effective conformational sampling is performed for a pharmacophore-based analysis. The method used in ChemDiverse is based on an explicit "on-the-fly" generation of conformers done at search time. A conformation is accepted or rejected based on a fast evaluation of steric... 

ChemDiverse supports two optional fast quality checks that can be applied to potential pharmacophores before they are added to the key. These checks exclude pharmacophores that are either too small relative to the whole molecule ( volume check) or are potentially inaccessible to a receptor interaction ( accessibility check). 

The use of pharmacophoric descriptors in enhancing the hit-to-lead properties of lead optimization libraries has been described (76). Pharmacophore fingerprints, based on the Chem-X/ChemDiverse multiple pharmacophore descriptors, were used and several issues in the design of lead optimization libraries were addressed. The applicability of... 

ChemDiverse pharmacophore descriptors substructure descriptors ( pharmacophore-... 

ChemDiverse was implemented within the Chem-X software package from Chemical Design Ltd., since 1998 part of the Oxford Molecular Group, since 2000 part of Accelrys Inc, 9685 Scranton Road, San Diego, CA 92121-3752, USA. 

ChemDiverse. Oxford Molecular Group pic. The Medawar Centre, Oxford Science Park, Oxford, 0X4 4GA, United Kingdom, http //www.oxmol.coni/. 

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