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28 Cards in this Set
- Front
- Back
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What is Lipinski's Rule of Five? |
Poor absorption or permeation occurs when: -There are more than 5 H-bond donors (OHs and NHs) -The Molecular weight is over 500 -The LogP is over 5 -There are more than 1- H-bond acceptors (Ns and Os) |
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What classes are exceptions to the Lipinski rule of five? |
Compound classes that are substrates for biological transporters. |
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What does QSAR stand for? |
Quantitative Structure-Activity Relationship |
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What is QSAR? |
Where you relate the biological activity of a series of compounds to their physicochemical parameters in a quantiative fashion using a mathematical formula -Requires quantitative measurements of biological activity and physicochemical properties |
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What things are most commonly studied in QSAR? |
• Hydrophobicity of the molecule (log P)• Hydrophobicity of substituents (pi)• Electronic properties of substituents (sigma)• Steric properties of substituents (Es) |
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What compounds is QSAR valid for? |
QSAR is only valid for compounds within the same structural class |
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What is the equation for the partition coefficient, P? |
[Drug in Octanol] P= -------------------------- [Drug in Water] |
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What does a higher log P value mean? |
That the drug is more hydrophobic |
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What does logP° stand for? |
The optimum value of log P for activity |
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What is the equaiton for Hydrophobicity constant, pi? |
. |
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What does a positive pi value indicate? |
The substituent is more hydrophobic than hydrogen |
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What does a negative pi value indicate? |
The substituent is less hydrophobic than hydrogen |
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What is a pi value valid for? |
Parent structures only |
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What is the Hammeett Substituent Constant (sigma)? |
A measure of the electron-withdrawing or electron-donating properties of a substituent |
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What is KH? |
The dissociation constant |
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What is the equation for KH? |
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What does Es stand for? |
Taft's Steric Factor |
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What is the equation for Taft's Steric Factor? |
Kx represents the rate of hydrolysis of a substituted ester Ko represents the rate of hydrolysis of the parent ester |
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What is Taft's Steric Factor limited to? |
-Substituents which interact sterically with the tetrahedral transition state for the reaction -Can't be used for substituents which interact with the transition state by resonance or hydrogen bonding -May undervalue the steric effect of groups in an intermolecular process |
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What does MR stand for |
Molar Refractivity |
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What is molar refractivity? |
A measure of a substituent's volume |
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What is the equation for Molar Refractivity, MR? |
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What is the Hansch Equation for a narrow range of Log P? |
Linear
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What is the Hansch Equation for a wide range of Log P? |
Parabolic |
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What does a Craig Plot allow? |
-Easy identification of suitable substituents for QSAR analysis including both relevant properties -Must choose a substituent from each quadrant to include in analogue synthesis to ensure orthogonality -Choose substituents with a range of values for each property to ensure validity of the study |
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What happens in 3D QSAR? |
• Physical properties are measured for the whole molecule• Properties are calculated using specialist software• No experimental constants or measurements are involved• Properties are known as ‘Fields’• Steric field - defines the size and shape of the molecule• Electrostatic field - defines electron rich/poor regions• Hydrophobic properties are relatively unimportant |
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What are the advantages of 3D QSAR? |
• No reliance on experimental values• Can be applied to molecules with unusual substituents• Not restricted to molecules of the same structural class |
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3D QSAR |
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