ClogP method

Chose, A. K., Viswanadhan, V. N., Wendoloski, 1.1. Prediction of hydrophobic (lipophilic) properties of small organic molecules using fragmental methods an analysis of ALOGP and CLOGP Methods./. Phys. Chem. 1998, A 102, 3752-3772. 

In the following, the atom/fragment contribution method (AFC method) developed by Meylan and Howard (1995) is used to illustrate the approach. This method is similar to the CLOGP method, but it is easier to see its application without using a computer program. Here, we confine ourselves to a few selected examples of fragment coefficients and correction factors. This will reveal how the method is... 

Ghose A K, V N Viswanadhan and J J Wendoloski 1998 Predichon of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragmental Methods An Analysis of ALOGP and CLOGP Methods Journal of Physical Chemistry 102 3762-3772. 

As a positive example, calculated log P values were used to rationalize the 5-HT a affinity of some N -imidoethyl derivatives of l-(2,3-dihydro-l,4-ben-zodioxin-5-yl)piperazines.2o Twelve congeners modified on the N -substituent were synthesized and their affinity for the 5-HTjy receptor [displacement of [ H]2-(di- -propylamino-8-hydroxytetralin)] measured. A reasonable QSAR equation (Eq. [40]) was obtained between the affinity constant (pK ) and log P calculated with the CLOGP method (Figure 19). The results showed that in this series affinity was predominantly driven by the hydrophobic character of the substituent. 

Of the physicochemical descriptors, lipophilicity (as described by clogP and Topological Polar Surface Area (TPSA) gave the strongest overall correlation to incidence of adverse in vivo outcomes, whether analyzed in terms of free or total drug threshold concentrations. In the case of free drug threshold analysis, a Random Forest statistical method indicated that there was a higher chance of a compound with TPSA <70... 

In which the terms Ha refers to the number of free electron pairs, MW is the molecular weight, and clogP is the computed lipophilicity. While this method could be stated to be "partially in silico" because it utilizes some chemical descriptors, the need for in vivo animal data and their dominance in the individual terms really makes this approach more of an animal-human correlation than an in silico method. Finally, in the same report, the authors describe a regression based solely in animal data. Overall, the performance of these... 

ClogP This method developed by Leo and Hansch presents some similarities with the method of Rekker, since the log P of a molecule is calculated by adding lipophUicity values attributed to multiatomic fragments and numerous corrections factors which take into account not only geometrical and topological effects but also electronic and steric effects (Equation 5.3) [39-41]. 

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