Back to: Organic Chemistry 400 Level
Welcome to class!
Hello brilliant learner, it’s truly a pleasure to continue this journey with you today. I hope you’re feeling focused and eager, because Medicinal & Pharmaceutical Organic Chemistry II will deepen your understanding of how drugs behave inside the body and how their structures are modified to improve therapeutic effectiveness. Today’s lesson will cover drug metabolism, structure–activity relationship (SAR) in more detail, and prodrugs – important concepts every advanced medicinal chemistry student must know.
Medicinal & Pharmaceutical Organic Chemistry II
Think of the drug as a traveller going on a journey in the body. To reach its destination (the biological target), it must pass through different checkpoints and may even need to change its clothes (structure) on the way so it can perform well. This is exactly what happens to drug molecules in the body.
Drug Metabolism (Biotransformation)
Drug metabolism refers to the chemical changes that occur to a drug once it enters the body. These reactions usually take place in the liver, and they help convert the drug into forms that are easier to remove from the body.
Drug metabolism occurs in two phases:
Phase I Reactions – Functionalisation reactions such as oxidation, reduction or hydrolysis. These reactions introduce or expose functional groups. For example, oxidation of paracetamol by cytochrome P450 enzymes.
Phase II Reactions – Conjugation reactions where the drug or its Phase I metabolite is linked to another molecule such as glucuronic acid, sulphate or glycine. This increases water solubility and facilitates excretion in urine.
You can think of Phase I as cutting open the package and Phase II as adding a label and wrapping, so it is ready to be transported out of the body.
Structure–Activity Relationship (SAR)
SAR is the process of studying the relationship between a drug’s chemical structure and its biological activity. This helps medicinal chemists understand which parts of the molecule are essential for activity and which parts can be modified.
Important concepts in SAR include:
Pharmacophore – The essential structural features required for biological activity.
Auxophore – The portions of the molecule that are not essential but influence potency, solubility or selectivity.
Bioisosteric Replacement – Replacing one functional group with another that has similar properties to improve the drug’s pharmacological profile; for example, replacing hydrogen with fluorine on an aromatic ring to increase metabolic stability.
This is similar to improving the design of a key so that it fits more perfectly into the lock and opens it more efficiently.
Prodrugs
A prodrug is an inactive or less active compound that is converted into the active drug after it enters the body. Prodrugs are designed to overcome limitations such as poor solubility, poor absorption or rapid metabolism.
Examples include:
Enalapril, which is converted in the body to the active drug enalaprilat, a potent antihypertensive agent.
Aspirin, which is converted to salicylic acid in the body and then produces its therapeutic effect.
You can think of a prodrug as a “masked version” of the drug that slips easily into the body and then reveals its true form when needed.
Drug–Receptor Binding Forces
Drug molecules bind to their receptors through several types of interactions:
Hydrogen bonds
Ionic interactions
Hydrophobic interactions
Van der Waals forces
The strength and combination of these forces determine how tightly and how selectively the drug binds to its target. Weak binding leads to poor activity, while strong and selective binding results in better therapeutic effects.
Summary
- Drug metabolism involves Phase I (functionalisation) and Phase II (conjugation) reactions that prepare drugs for elimination.
- Structure–Activity Relationship (SAR) examines how structural changes influence biological activity and helps identify pharmacophores and improve drug effectiveness.
- Prodrugs are inactive forms of drugs designed to overcome poor pharmacokinetics and become active after administration.
- Bioisosteric replacement is a useful strategy in drug design to improve potency and metabolic stability.
- Drug–receptor binding is governed by interactions such as hydrogen bonding, ionic and hydrophobic forces.
Evaluation
- What is the main purpose of drug metabolism in the body?
- Explain the difference between a pharmacophore and an auxophore.
- Define a prodrug and give one example.
- Mention two types of interactions involved in drug–receptor binding.
Excellent work today! You are developing a strong understanding of medicinal chemistry concepts and Afrilearn is proud of your dedication. Keep this momentum — your next lesson will take you even further into the science of drug discovery and development!