What is the Lipophilicity constant?
Lipophilicity (from Greek λίπος “fat” and φίλος “friendly”), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene.
What is substituent hydrophobicity constant?
The substituent hydrophobicity constant is a measure of how hydrophobic a substituent is, relative to hydrogen. A positive value of π indicates that the substituent is more hydrophobic then hydrogen. A negative value indicates that the substituent is less hydrophobic.
How do you determine the lipophilicity of a drug?
Lipophilicity plays a significant role in drug discovery and compound design. The lipophilicity of an organic compound can be described by a partition coefficient, logP, which can be defined as the ratio of the concentration of the unionized compound at equilibrium between organic and aqueous phases.
How does Lipophilicity affect drug distribution?
Lipophilicity is an important physicochemical parameter that contributes to the absorption, distribution, metabolism, excretion, and toxicity of a drug. This often leads to compounds that have a high rate of metabolism, leading to poor solubility, high turn-over, and low absorption.
How does fluorine increase Lipophilicity?
Adding fluorine to biologically active organic compounds increases their lipophilicity (ability to dissolve in fats), because the carbon–fluorine bond is even more hydrophobic than the carbon–hydrogen bond. This effect often increases a drug’s bioavailability because of increased cell membrane penetration.
How does Lipophilicity affect permeability?
Lipophilicity has also been found to affect a number of pharmacokinetic parameters: higher lipophilicity gives, in general, lower solubility, higher permeability in the gastrointestinal tract, across the blood–brain barrier and other tissue membranes, higher affinity to metabolizing enzymes and efflux pumps, and higher …
What is substituent constant?
The substituent constant is a measure of the total polar effect exerted by substituent X (relative to no substituent) on the reaction centre. Electron-withdrawing m-NO2 ( = +0.71) increases stability of tetrahedral intermediate compared to electron- donating m-CH3 ( = -0.07).
What does the Hammett substituent constant σ measure?
The reaction constant, or sensitivity constant, ρ, describes the susceptibility of the reaction to substituents, compared to the ionization of benzoic acid. It is equivalent to the slope of the Hammett plot. Information on the reaction and the associated mechanism can be obtained based on the value obtained for ρ.
How can Lipophilicity be altered?
Addition of two acetyl groups to produce heroin further increases BBB permeation, because of increased lipophilicity, despite increasing the number of H-bond acceptors. Nonpolar groups (e.g., methyl) can be added to a molecule to enhance lipophilicity. Figure 10.12. Effects of lipophilicity on BBB permeation .
How do you increase lipophilicity of a drug?
First-Pass Metabolism Considerations in Pharmaceutical Product Development
- Prodrugs are used to increase lipophilicity so that the drugs are available for oral administration, ocular, or topical drug delivery.
- The acyl ester of ganciclovir (Fig.
- Lipophilic prodrugs are also used to enhance ocular absorption.
How does fluorine increase lipophilicity?
Does lipophilicity affect half-life?
For example, a decision to lower the lipophilicity in an attempt to increase half-life may result in decreasing half-life.
What is lipophilic in chemistry?
Lipophilicity (from Greek λίπος “fat” and φίλος “friendly”), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipophilic (translated as “fat-loving” or “fat-liking” ), and the axiom that “like dissolves like” generally holds true.
What is the partition coefficient of lipophilicity?
18.104.22.168 Lipophilicity and Polarizability. The lipophilicity of a molecule is expressed as a partition coefficient (Log P or π) of an n -octanol/water system, where more lipophilic compounds are partitioned in the n -octanol layer.
How does lipophilicity affect solubility and stability?
For example, increasing permeability by increasing lipophilicity may decrease solubility and metabolic stability. An example of lipophilicity structural modification that affects permeability is as follows.
How do you calculate Lipophilicity from octanol?
The lipophilicity of a substance is often evaluated by using its log P octanol value, which is the logarithm of its octanol/water partition coefficients. This value is quite representative of the ability of a molecule to pass through a lipidic membrane.