ClogP value

Measured log Ps and CLOGP values are from BioByte software KOWWIN values were calculated from version 1.5 ACD values calculated using ver. beta 0.9 ALOGP,... 

FIGURE 27.15 The median MW and cLogP values for DMLs are higher dian those for oral dmgs or a general set of prechnical compounds from Organon s SCOPE database. ... 

Remove molecules with a ClogP value outside the 0—6 range. 

QSAR 8 mentioned earlier was derived for the same dataset [75]. Ionization potential (IP), ClogP, molar volume (as MV/lOO) and an indicator variable (1) were used to model the activity. A parabolic model with ClogP unfolded the ideal ClogP value (ClogPo = 5.697) for maximum anti-protease activity. It is of note that the activities of the test set compounds (total eight) were predicted well both by the 2D-QSAR model (r = 0.746) of Wilkerson et al. [75] and the CoMFA model (r = 0.971) of Debnath [99]. 

The majority of HIV research is done with cells and these studies tend to over estimate the value of logPo (i.e., 1 or 2 log unit higher) for whole organisms [253]. A study of the ClogP value of approved HIVPI drugs emphasizes this observation. 

Here S is the solvent-accessible surface area for atom /, a, is the hydrophobic atom constant for atom /, and R , = e, where r is the distance between atom i and grid point t. In addition to supplementing standard CoMFA fields, HINT has been demonstrated to effectively model experimentally determined log P values in cases where CLOGP values fail. A different fragment-based, distance-dependent method to estimate lipophilicity, the molecular lipophilic potential (MLP), has been recently shown to be useful in docking and as a third field in CoMFA studies. 

Figure 749 Acetaminophen has a phenol group that is subject to phase II metabolic conversion into a sulfate conjugate.This changes the ClogP value from +0.49 in the drug to -0.84, increasing the water solubility. This is the major urinary metabolite found in children in whom acetaminophen was administered. (ClogP values were determined using ChemBioDraw Ultra 13.0, Perkin Elmer Informatics, Waltham, MA).

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