Solvation enthalpies as descriptors of structure--in vitro percutaneous permeation relationship of benzoxazinones regioisomers
| Autor: | Francesco Cilurzo, Giorgio Bertolini, Andrea Zaliani, Antonella Casiraghi, Luisa Montanari, M. Valmen Monzani, Paola Minghetti |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Octanol
Hydrogen bond Stereochemistry Benzoxazinones Chemistry Enthalpy Substituent Solvation Pharmaceutical Science Permeability Enthalpy change of solution chemistry.chemical_compound Structure-Activity Relationship Isomerism Drug Discovery Structural isomer Solvents Physical chemistry Humans Thermodynamics Skin |
| Zdroj: | Farmaco (Societa chimica italiana : 1989). 55(8) |
| ISSN: | 0014-827X |
| Popis: | The aim of this work was to correlate the in vitro human skin permeability, expressed as the permeability coefficient ( K p ), and some physicochemical parameters of a new series of benzoxazinones. The in vitro human skin permeability of 14 substances, including regioisomers with CH 3 , OH, OCH 3 , and Cl groups in different positions on the aromatic ring, was determined. The modified Franz diffusion cell method was used. The K p values were in the range 0.14–8.24 cm/h, showing a strong dependence on the position and type of substituent. Physicochemical descriptors usually referred in literature, such as log P , molecular weight and volume (MV), hydrogen bond donor ( H d ) and acceptor activity ( H a ), and molecular refractivity were considered, with the addition of solvation enthalpy (ΔΔ H solv ). ΔΔ H solv is defined as the difference between formation enthalpies in water and octanol. The algorithm with the best correlation between K p and physicochemical descriptors was calculated, taking into account the differences observed among the regioisomers. The algorithm obtained with ΔΔ H solv had a good correlation ( r 2 =0.749, F =16.43, P =0.0005), comparable with the equation, proposed by Potts and Guy, based on MV, H d and H a ( r 2 =0.830, F =16.3, P =0.0004). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect