Linear Relationships between Lipophilic Character and Biological Activity of Drugs

Hansch, Corwin; Dunn, William J.

doi:10.1002/jps.2600610102

Cited by 438 publications

(111 citation statements)

References 63 publications

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“…It has become an essential tool for the understanding of the tendency of a chemical to cross biological membranes. It is an important parameter since it describes the hydrophobic/hydrophilic balance of a compound thus assessing in a simple way, the transport of an API in the distribution and its affinity for cell membranes (Hansch and Dunn, 1972;Leo et al, 1971; Table 2 Solubility of l-ampicillin, ampicillin sodium salt and ampicillin-based ILs (mean and standard deviation), in water at 25 • C and 37 • C.…”

Section: Water Solubility and Octanol-water Partition Coefficientmentioning

confidence: 99%

“…This last parameter represents the delicate balance between the different thermophysical properties and influences the bioavailability of a drug, as well as its toxicity and half-life features. The octanol-water partition coefficient (K ow 's) is the classic method to access hydrophilic/lipophilic balance (Hansch and Dunn, 1972;Leo et al, 1971) and it is the most used parameter in drug development quantitative structureactivity relationship models. However, the isotropic nature of octanol makes it a poor mimetic system for biomembranes.…”

Section: Introductionmentioning

confidence: 99%

“…The study of the combination of an API with an ionic liquid possessing surfactant activity is important because novel therapies using surfactant API-ILs as drug delivery devices can offer interesting avenues to be explored (Bernardes et al, 2011;Hansch and Dunn, 1972;Liu et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of solubility and partition properties of ampicillin-based ionic liquids

Florindo

Araújo

Alves

et al. 2013

International Journal of Pharmaceutics

107

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a b s t r a c tIn order to overcome the problems associated with low water solubility, and consequently low bioavailability of active pharmaceutical ingredients (APIs), herein we explore a modular ionic liquid synthetic strategy for improved APIs. Ionic liquids containing l-ampicillin as active pharmaceutical ingredient anion were prepared using the methodology developed in our previous work, using organic cations selected from substituted ammonium, phosphonium, pyridinium and methylimidazolium salts, with the intent of enhancing the solubility and bioavailability of l-ampicillin forms. In order to evaluate important properties of the synthesized API-ILs, the water solubility at 25 • C and 37 • C (body temperature) as well as octanol-water partition coefficients (K ow 's) and HDPC micelles partition at 25 • C were measured. Critical micelle concentrations (CMC's) in water at 25 • C and 37 • C of the pharmaceutical ionic liquids bearing cations with surfactant properties were also determined from ionic conductivity measurements.

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Section: Water Solubility and Octanol-water Partition Coefficientmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of solubility and partition properties of ampicillin-based ionic liquids

Florindo

Araújo

Alves

et al. 2013

International Journal of Pharmaceutics

107

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“…Partition coefficients The partition coefficients of the cardiac glycosides were determined in octanol/water (20 mmol I' Tris/HCI-buffer, pH 7.4) at room temperature according to the shake-flask method of Hansch & Dunn (1972 The cardiotonic steroids examined (Table 1) were purchased from Merck (F.R.G.) or Roth (F.R.G.).…”

Section: Lipophilicitymentioning

confidence: 99%

“…water-saturated solvents and a solvent-saturated water phase, have been put up in order to resemble biological partition systems for the purpose of studying the partitioning behaviour of a number of drug-classes. Widest recognition has been accredited to the octanol/water (Trisbuffer/HCI, pH 7.4) system as most closely resembling physiological partition systems (Leo et al, 1971;Hansch & Dunn, 1972;Smith et al, 1975). However the conventional shake-flask method used to determine the partition coefficients is tedious, time-consuming and very susceptible to technical error, especially within the ranges of 10> P <1000 (Cohnen et al, 1978;Rogatti, 1983a).…”

Section: Introductionmentioning

confidence: 99%

Influence of derivation on the lipophilicity and inhibitory actions of cardiac glycosides on myocardial Na⁺‐K⁺‐ATPase

Dzimiri

Fricke

Klaus

1987

British J Pharmacology

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1 Lipophilicity and inhibitory actions on guinea-pig heart Na'-K+-ATPase of twenty-six digitalis and six strophanthus glycosides comprising the aglycones, mono-, bis-, tris-sugar, alkylated (acylated) tris-sugar, acyl steroid derivatives and three cardanolides were investigated. 2 Their octanol/water partition coefficients (P), reversed phase thin layer (r.t.l.c.) and reversed phase high performance liquid chromatography (r.h.p.l.c.) were determined and the viability of these methods as a measure of the lipophilicity of the cardiotonic steroids evaluated. 3 The influence of lipophilicity and so also structural changes on the inhibitory effects of the cardiac glycosides on myocardial Na+-K+-ATPase was then examined. 4 It is concluded that (a) r.t.l.c. and r.h.p.l.c. are just as effective as the conventional shake-flask method for estimation of the lipophilicity of cardiac glycosides and (b) the inhibitory potencies of cardiotonic steroids on the myocardial Na+-K+-ATPase increase with growing lipophilicity. The relationship between these two parameters is, however, governed by the influence of substitution or derivation of structural components on their inhibitory potencies on the myocardial Na+-K+-ATPase.

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A Model-based Dependence of the Human Tissue/Blood Partition Coefficients of Chemicals on Lipophilicity and Tissue Composition

Baláž¹,

Lukáčová

1999

Quant. Struct.-Act. Relat.

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Partitioning of up to thirty-six nonionizable chemicals between seven tissues (fat, liver, brain, kidney, muscle, lung, heart) and blood in humans was modeled using membrane accumulation, protein binding, and distribution in the aqueous phases as relevant processes. The extent of membrane accumulation and protein binding of individual compounds was described as the Collander-type function of their lipophilicity expressed by the 1-octanolywater partition coef®cients. The resulting model-based expression described satisfactorily the tissueyblood partition coef®-cients as a nonlinear function of lipophilicity and tissue composition (a standard content of lipids, proteins, and water). The calibrated model is suitable for prediction of the tissueyblood partition coef®cients for non-amphiphilic nonionizable chemicals with the 1-octanolywater partition coef®cients varying between 0.01 and 100,000, i.e. practically in the whole range for which equilibrium tissueyblood distribution can be used in physiologically based pharmacokinetic models.

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Linear Relationships between Lipophilic Character and Biological Activity of Drugs

Cited by 438 publications

References 63 publications

Evaluation of solubility and partition properties of ampicillin-based ionic liquids

Evaluation of solubility and partition properties of ampicillin-based ionic liquids

Influence of derivation on the lipophilicity and inhibitory actions of cardiac glycosides on myocardial Na⁺‐K⁺‐ATPase

A Model-based Dependence of the Human Tissue/Blood Partition Coefficients of Chemicals on Lipophilicity and Tissue Composition

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Linear Relationships between Lipophilic Character and Biological Activity of Drugs

Cited by 438 publications

References 63 publications

Evaluation of solubility and partition properties of ampicillin-based ionic liquids

Evaluation of solubility and partition properties of ampicillin-based ionic liquids

Influence of derivation on the lipophilicity and inhibitory actions of cardiac glycosides on myocardial Na+‐K+‐ATPase

A Model-based Dependence of the Human Tissue/Blood Partition Coefficients of Chemicals on Lipophilicity and Tissue Composition

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Influence of derivation on the lipophilicity and inhibitory actions of cardiac glycosides on myocardial Na⁺‐K⁺‐ATPase