Framework combination

MMVB is a hybrid force field, which uses MM to treat the unreactive molecular framework, combined with a valence bond (VB) approach to treat the reactive part. The MM part uses the MM2 force field [58], which is well adapted for organic molecules. The VB part uses a parametrized Heisenberg spin Hamiltonian, which can be illustrated by considering a two orbital, two electron description of a sigma bond described by the VB determinants... 

Porous oxide catalytic materials are commonly subdivided into microporous (pore diameter <2nm) and mesoporous (2-50 nm) materials. Zeolites are aluminosilicates with pore sizes in the range of 0.3-1.2 nm. Their high acidic strength, which is the consequence of the presence of aluminium atoms in the framework, combined with a high surface area and small pore-size distribution, has made them valuable in applications such as shape-selective catalysis and separation technology. The introduction of redox-active heteroatoms has broadened the applicability of crystalline microporous materials towards reactions other than acid-catalysed ones. 

The screening and framework combination approaches to lead generation have various advantages and disadvantages that influence which one is best applied to a particular... 

TABLE 27.2 Features of the Screening and Framework Combination Approaches to DMLs ... 

Can provide ligands with complex profiles unavailable by framework combination Can employ existing SAR knowledge from selective ligand projects to assess feasibility and facilitate optimization... 

Can provide ligands with improved physicochemical and pharmacokinetic properties compared to framework combination Can readily provide linked DMLs for use as i.v. drugs or biochemical tools, even for two targets with incompatible pharmacophores... 

Using a framework combination approach, compounds with dual 5-HTia/SERT activity were designed by Mewshaw et al, starting from a template known to possess... 

The MW for screening-derived DMLs is frequently lower than for the framework combination strategy, suggesting that this approach may provide a route to smaller and less complex leads (Figure 27.17). A starting compound... 

FIGURE 27.19 Linked DMLs derived via a framework combination approach can make useful biochemical tools or i.v. administered drugs. 

Can provide ligands with complex profiles unavailable by framework combination... 

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