Search for notes by fellow students, in your own course and all over the country.
Browse our notes for titles which look like what you need, you can preview any of the notes via a sample of the contents. After you're happy these are the notes you're after simply pop them into your shopping cart.
Title: Oral bioavailability of drugs-Lipinski and Webers rules
Description: Aimed at degree students studying modules in medicinal chemistry, these notes focus on Lipinski and Weber rules, which are predictors of good oral bioavailability of drugs.
Description: Aimed at degree students studying modules in medicinal chemistry, these notes focus on Lipinski and Weber rules, which are predictors of good oral bioavailability of drugs.
Document Preview
Extracts from the notes are below, to see the PDF you'll receive please use the links above
Lipinski and Veber rules
The Lipinski and Veber rules are rules for compounds being investigated for
drug discovery
...
Lipinski rules
Lipinski’s rules of 5 are as follows…the drug should have
• A molecular weight <500
• A value of logP<5
• Less than 5 –OH or –NH groups (hydrogen bond donors) in total
• Less than 10 O or N atoms in total (hydrogen bond acceptors
Explained
• A molecular weight of less than 500
...
Presumeably due to compound size
• P is the partition coefficient, a measure of hydrophobicity
...
• 5 –OH and –NH bonds, and 10 O or N atoms is to determine hydrogen
bonding
...
This is
key to its water solubility, but these bonds must be broken if it is to cross
the lipid membranes
...
• On average, commercial drugs have molecular weight of 360, an average
of 2
...
3 O and N atoms, and a lop
value of 1
...
Veber rules
Veber et al, in a paper released in 2002, proposed the following:
• 10 or fewer rotatable bonds (though if its less than 7, oral bioavailabilty is
much greater than 7 or more)
• Less than 12 H bond donors or acceptors in total
• A polar surface area of less than 140 A (angstroms) squared
• These rules don’t give a molecular weight value
Why are the rules important-‐a bit on oral bioavailability
There are many different drug administrative routes-‐intravenous, subcutaneous,
intramuscular…but arguably the best is oral, because it doesn’t involved sticking
a needle into the body and all the risks associated with that
...
Notably digestion
...
Not only this, but the drug has to be absorbed
...
However this has to be finely balanced
...
Not soluble enough and, depending on the compound, it
might precipitate somewhere like the kidneys
...
Not soluble enough in fats, and it doesn’t cross the
membranes
...
4 to +5
...
As such a “rule of 3” has been
proposed for lead-‐like compounds, which allows some room for variation:
• LogP less than 3
• Molecular weight under 300
• No more than 3 hydrogen bond donors
• No more than 3 hydrogen bond acceptors
• No more than 3 rotatable bonds
Known compounds that people want to investigate for potential as a lead
compound should fit these rules, ideally
...
This requires analysis
of the pharmacophore to determine the optimal structure and
interactions for the target
...
• Rule out the drug from use
...
Some drugs don’t conform with Lipinski rules
but are absorbed anyway
...
Antibiotics and lipid soluble vitamins,
for example, are absorbed by transporters, or in the case of the vitamins,
absorbed with lipids
...
Title: Oral bioavailability of drugs-Lipinski and Webers rules
Description: Aimed at degree students studying modules in medicinal chemistry, these notes focus on Lipinski and Weber rules, which are predictors of good oral bioavailability of drugs.
Description: Aimed at degree students studying modules in medicinal chemistry, these notes focus on Lipinski and Weber rules, which are predictors of good oral bioavailability of drugs.