Med chem Flashcards
How do we calculate TI?
For this course, TI=TD50/ED50. A higher TI is better.
What is EC50?
Half the maximal effective concentration of a drug
What is IC50?
The concentration of a drug at which half of all activity is inhibited
What does ADMET stand for?
Absorption, Distribution, Metabolism, Excretion, Toxicity
When do we use ADMET?
During lead optimisation - it represents five very important factors to consider for any drug.
What are Lipinski’s “rules of 5”?
The molecule should have a mass of less than 500amu, should have at most 5 H-bond acceptors and at most 10 H-bond donors, and should have a logP of less than 5
What is logP?
P is the ratio of the concentration of the drug in octanol vs water. It helps us identify whether a molecule is more lipid-soluble vs water-soluble.
What does QED stand for?
Quantitative Estimate of Druglikeness
What additional parameters does QED incorporate other than Lipinski’s rules?
The molecule should have as few fused cyclic system as possible, a polar surface area of less than 140 square angstroms, less than 5 rotatable bonds, and a low number of aromatic rings.
How is QSAR used in the drug development process?
QSAR allows us to determine the likely activity of a molecule for a particular purpose based on structural features.
What are the key factors considered in QSAR?
We use logP to check hydrophobicity, the Hammett constant for electronics, and Taft’s steric factor for sterics.
What is the Hammett constant?
The Hammett constant is the ratio between the acid dissociation constant for a molecule with a given R-group substituent and the same molecule with a hydrogen in place of the R-group. This tells us relatively how electron-withdrawing the R-group is.
What is Taft’s steric factor?
Taft’s steric factor is calculated by comparing the rate constant for a reaction with the molecule containing an R-group substituent vs the same molecule with some “default substituent” in that position. Higher steric factor implies that the R-group makes things more sterically accessible.
What reagents are involved in a Suzuki-Miyaura coupling?
Organoborates and organohalides (one of which is aryl)
What reagents are involved in a Nigishi coupling?
Organozinc and organohalides (one of which is aryl)
