Journal ArticleDOI
Structure-Lipophilicity Relationships of Neutral and Protonated β-Blockers, Part I, Intra- and Intermolecular Effects in Isotropic Solvent Systems
Giulia Caron,Guillaume Steyaert,Alessandra Pagliara,Frédéric Reymond,Patrizia Crivori,Patrick Gaillard,Pierre-Alain Carrupt,Alex Avdeef,John Comer,Karl J. Box,Hubert H. Girault,Bernard Testa +11 more
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TLDR
In this paper, the inter-and intramolecular forces influencing the partitioning behavior of β-blockers in isotropic biphasic solvent systems were investigated, and the relevance of these parameters in structure-permeation relationships was explored.Abstract:
The objectives of this study were to validate new experimental techniques used to measure the log P of protonated drugs, and to investigate the inter- and intramolecular forces influencing the partitioning behavior of β-blockers in isotropic biphasic solvent systems. The lipophilicity parameters of a number of β-blockers were measured by two-phase titration, centrifugal partition chromatography (CPC), and cyclic voltammetry (CV) in one or more of the following solvent systems: octanol/water, 1,2-dichloroethane/water, and dibutyl ether/water. CV proved to be a promising technique for measuring the lipophilicity of protonated β-blockers. Derived parameters such as Δlog P (difference between log P in two different solvent systems, a parameter valid for a given solute in a given electrical form) and diff (difference between log P of two different electrical forms of a given solute, in the same system) yielded insights into inter- and intramolecular interactions characteristic of β-blockers. The relevance of these parameters in structure-permeation relationships is explored.read more
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Journal ArticleDOI
Physicochemical Profiling (Solubility, Permeability and Charge State)
TL;DR: This review will consider recent developments in physicochemical profiling used to identify candidate molecules with physical properties related to good oral absorption and focus on the emerging instrumental methods for the measurement of the physicochemical parameters Pe, S, pKa, R, log P, and log D (and their pH-profiles).
Journal ArticleDOI
Lipophilicity and Its Relationship with Passive Drug Permeation
TL;DR: The broad evidence presented here shows that beyond the predictive power of lipophilicity parameters, the various intermolecular forces they encode allow a mechanistic interpretation of passive drug permeation.
Journal ArticleDOI
Carvedilol and its new analogs suppress arrhythmogenic store overload-induced Ca2+ release.
Qiang Zhou,Jianmin Xiao,Jianmin Xiao,Dawei Jiang,Ruiwu Wang,Kannan Vembaiyan,Aixia Wang,Christopher Smith,Cuihong Xie,Cuihong Xie,Cuihong Xie,Wenqian Chen,Jingqun Zhang,Xixi Tian,Peter P. Jones,Peter P. Jones,Xiaowei Zhong,Ang Guo,Haiyan Chen,Lin Zhang,Weizhong Zhu,Dongmei Yang,Xiaodong Li,Ju Chen,Anne M. Gillis,Henry J. Duff,Heping Cheng,Heping Cheng,Arthur M. Feldman,Long-Sheng Song,Michael Fill,Thomas G. Back,S. R. Wayne Chen,S. R. Wayne Chen +33 more
TL;DR: It is shown that carvedilol is the only beta blocker tested that effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor (RyR2) and this unique anti-SOICR activity of carveilol probably contributes to its favorable antiarrhythmic effect.
Journal ArticleDOI
Physicochemical Profiling (Solubility, Permeability and Charge State)
TL;DR: This review will consider recent developments in physicochemical profiling used to identify candidate molecules with physical properties related to good oral absorption and focus on the emerging instrumental methods for the measurement of the physicochemical parameters Pe, S, pKa, R, log P, and log D (and their pH-profiles).
Journal ArticleDOI
Drug permeation in biomembranes: In vitro and in silico prediction and influence of physicochemical properties
TL;DR: A general overview of the approaches aimed at predicting biological permeation, one of the cornerstones behind the ADME behaviour of drugs, is given.
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