Scaffold replacement

CAVEAT (39, 40) are examples of software using the linking approach. ReCore (41) and Scaffold Replacement are capable of performing both fragment linking and building. 

J. Leonard and N. Thorsteinson, in Novel scaffold replacement methodology applied to the discovery of P38 MAP kinase inhibitors, 2010, ACS Fall Meeting, abstract COMP-252. 

Chemists will understand that the simple change of a heterocyclic scaffold can involve completely different and often difficult synthetic routes. Those who ve tried these kinds of substitutions will also understand that most of the time such a change will result only in a massive loss of activity, and modelers will understand that it s usually difficult to say why. So no one should view any proposed heterocyclic scaffold replacement as a sure thing . That being said, apparent examples of heterocyclic core switching can also be found in the COX2 inhibitors shown in Figure 8.15 like celecoxib, valdecoxib, rofecoxib, and etoricoxib. 

Scaffold Replacement replace a portion of the hgand with a linker... 

The user indicates the atoms or bonds to be replaced or extended and can specify ( SAR Descriptor, Model file and/or pharmacophore query filters to hmit the results. For example, a pharmacophore query can be used to enforce specific interactions (or restrictions) on the generated stractures when growing in a receptor pocket. Scaffold Replacement can be used as part of a hgand-based or structure-based discoveiy methodology. 

Thus, the scaffold-replacement approach afforded two GMl mimics that share the exceptional GT-binding properties of the natural template, while reducing the structural complexity and the sugar-like character of GMl-os. 

Equipment that can be reached for inspection, repair, or monitoring from permanent platforms is more likely to be inspected, calibrated, and replaced than equipment that requires climbing with a safety harness or scaffold. 

Merck has recently utilised a furo[2,3-b]pyridine core (554) as a bioisosteric replacement for the pyrazole scaffold of rimonabant (382) [328]. The same basic pharmacophore, that of two halo-substituted aryl groups and a third hydrophobic motif proximal to a hydrogen-bond acceptor, can be witnessed in the benzodioxole-based compounds, such as (555), disclosed by Roche [329]. 

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