Lecture 1: Introduction to Medicinal Chemistry Ionization of Drugs Flashcards
How do you identify the pharmacophore from the structure of drugs with similar biological activities?
Any drug that will bind to the same target, will share a similar structural motif.
The structural motif is mostly responsible for the binding to the receptor.
EX: Morphine, Fentanyl are agonist and Naloxone is an antagonist, but are all pharmacophores.
What is the structure-activity relationship?
Structure determines activity. By modifying the structure, one can change the drug properties. By examining the structure, one can predict the drug properties.
What are the key chemical properties of drugs that can be deduced from the structure?
Size, Ionization, Solubility, Hydrophobicity and Stereochemistry.
What are the key chemical properties of drugs that affect their biological activities?
Membrane permeability, Target binding, Metabolism and Excretion.
What are the drug properties that are affected by the change in pH?
Ionization, Solubility.
What are the ionized groups in drug structure?
Common: Weak acids and bases such as carboxylic acids, alcohols, amines.
How can you predict the ionized form of drugs from their structures?
Based of the functional groups and the what type of solution the drug will be in.
How would you estimate the degree of drug ionization at a given pH using Henderson-Hasselbalch equation?
When when the concentration of the weak acid is = to the concentration of the weak base pH = pKa of the weak acid. (Equal base and acid)
When when the concentration of the weak acid is > the concentration of the conjugate base pH < pKa of the weak acid. (Less base more acid)
When when the concentration of the weak acid is < the concentration of the conjugate base pH > pKa of the weak acid. (Less acid more base).
How would you predict the range of pH where a drug would be more soluble in water?
The pH range of extracellular fluid will be around 7.4 so drugs with a pKa under 7 (weak acids) will be more water soluble.
