The lipophilic behaviour of organic compounds:2. The development of an aliphatic hydrocarbon/water fragmental system via interconnection with octanol-water partitioning data

Abstract

A hydrophobic fragmental system was developed for application in the study of aliphatic hydrocarbonywater (ahcyw) partitioning. The ®nal version presented here is based on an optimized coupling of the ahcyw-system with f-constants for octanolywater partitioning. A total of 70 fvalues are now available in the aliphatic hydrocarbonywater system. The aliphatic hydrocarbonywater system appears to be especially useful in the evaluation of log P oct data for compounds with comparatively high lipophilicity.As a ®rst, preliminary validity check the new system is applied to pharmaco-chemical studies on penetration of blood-brain barrier by drugs and simple organic compounds. 537 Quant. Struct.-Act. Relat., 17 (1998) # WILEY-VCH Verlag GmbH, D-69469 Weinheim 0931-8771/99/0510-0372 $17.50+.50/0The lipophilic behaviour of organic compounds QSAR 1 Partitioning SystemsLipophilicity is traditionally measured in the octanolywater system. However, other solvent pairs have been used for particular purposes and for particular sets of compounds.

Application of Hansch's Model to Guaianolide Ester Derivatives: A Quantitative Structure−Activity Relationship Study

“…However, the asymmetry induced in the R face by the hydroxyl group in the 5R-hydroxyisozaluzanin C series log(1/EC 50 ) ) -0.0257(logP) 2 + 0.1883logP + 0.6098; n ) 4, R 2 ) 0.9318 (4) log(1/EC 50 ) ) -0.0529(logP) 2 + 0.3797logP + 0.464; n ) 3, R 2 ) 1.000 (5) (compounds 18-34) can explain the marked "even-odd" effect observed with the EC 50 : one of the two series will pack better than the other due to restrictions caused by the hydroxyl group ( Figure 7A). These differences should be present also in the isozaluzanin C series (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17), but the presence of the hydroxyl group at C-5 in the second series (18-34) will enhance this effect.…”

“…Lipophilia is a key factor in the absorption of any bioactive compound as it determines its bioavailability in the cell. Also, lipophilia is usually expressed through the logarithm of the octanol−water partition coefficient (log P ) ( , ) and is present in many quantitative structure−activity relationships (QSAR) equations because an optimum equilibrium between water, the usual carrier, solubility, and lipophilia (measuring of the ability to cross cell membranes) must exist. Hence, log P is an important parameter in the design of pesticides because it is related with the transport of the xenobiotics in plants ( − ).…”

Studying Retention Behavior, Lipophilicity and Pharmacokinetic Characteristics of N-Substituted Phenyl-2-Chloroacetamides

“…According to data from Table 6, the best agreement is obtained when Alog Ps and log Pch.s are correlated, while a linear dependence was not observed in the correlation values kowwin with other log P values. This phenomenon can probably be explained by the fact that all of the calculated values of log P, except the kowwin, were obtained by the method, which takes into account the contribution of individual fragments in the molecule [29]. The value kowwin was obtained by the method that is based on the impact and the contribution of the individual atoms in the molecule [30].…”

Pharmacokinetics

“…In the design of new compounds as well as the design of experimental procedures, an a priori calculation of log P or log D values is useful. Methods may be based on the summation of fragmental [44][45][46] or atomic contributions [47][48][49], or a combination of these [50,51]. Many other methods continue to be advanced, but commercial software usually uses either fragment-based (clog P) or atom-based (alog P) methods and these have become standardized with clog P usually favored.…”