Lipinski ‘rule

In both variants of the approach, i) and ii), the ligands detected in a NMR screen would be subjected to further modifications, and become larger during the design process. The properties of the compound library need to fulfill therefore a number of NMR-specific requirements. The compounds need to be soluble in water, their molecular properties should not exceed half the number that is defined in the Lipinski rules for molecular... 

Molecular size can be a further limiting factor in oral absorption [54]. The Lipinski Rule-of-5 proposes an upper limit of molecular weight (MW) of500 as acceptable for orally absorbed compounds [25]. High-MW compounds tend to undergo biliary excretion. Size and shape parameters are generally not measured, but rather calculated. A measured property is the so-called cross-sectional area, which is obtained from surface activity measurements [55]. 

To maximize the chances of success, it is necessary to build in drug-like properties. One of the drug-like criteria adopted is the Lipinski Rule of 5 — so named because of its emphasis on the number 5 and multiples of 5. The rule states that potential drug candidates are likely to have poor absorption and permeability if they have ... 

Several different approaches have been used to generate druglikeness prediction tools. The simplest approach is to identify a range of descriptor values for druglike compounds. The best known example of this approach is the Lipinski rules [16], which predict poor... 

Figure 13.2 Relationships of basic physicochemical properties of drug molecules, as observed by Lipinski etal. [13]. The green arrows suggest limits for the respective properties that were proposed in the Lipinski rules. ...

TABLE 1 Lipinski Rule of Five for Orally Active Compounds... 

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