Benzodiazepines physicochemical properties

Transport of the benzodiazepines into the brain is rapid, the rate of uptake being determined by the physicochemical properties of the drug. Absorption from the gastrointestinal tract, or from an injection site, is the rate-limiting step governing the speed of onset of the therapeutic response. Oral absorption is more rapid when the drug is taken on an empty stomach. 

Physicochemical Properties and References for the Structural Elucidation of Benzodiazepine Alkaloids... 

Many physicochemical properties can be used as a filter to discard unwanted molecules. However, strict filters can be unsatisfactory. For example, a molecule of molecular weight 399 may be accepted, whilst that of 401 rejected. If the latter molecule contained a novel 3D core, and the former was yet another benzodiazepine or aryl-amide-aryl-amine type, one might question the decision. Therefore, researchers adopted more subtle penalty functions. which increase the further away a molecule is from the ideal. Figure 14.4 illustrates the most common penalty functions. 

The computational construction of artificial neural networks has also been applied to relate physicochemical parameters of benzodiazepines with their receptor affinity and to predict BZR properties and BZR ligand affinities. In a study by Maddalena and Johnston, back-propagation artificial neural networks were used to examine the QSAR between substituent constants at six positions on 57 ben-zodiazepinones with their empirically determined binding affinities (118). Among the findings of the study were the following ... 

The physicochemical and pharmacokinetic properties of the benzodiazepines greatly affect their clinical ntility. They all have high lipid-water distribntion coefficients in the nonionized form nevertheless, lipophilicity varies more than 50-fold according to the polarity and electronegativity of varions snbstitnents. 

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