๐งช Introduction
Welcome to the “Introduction to Medicinal Chemistry” paper of MSc Chemistry 4th Semester (BAMU University syllabus).
In this post, we begin Unit 1 – Basic Consideration of Drug Activity, an important topic that helps you understand how and why drugs work in the body.
This Part 1 covers simple and clear notes on important medicinal chemistry terms such as Drug, Prodrug, Hard and Soft Drugs, Agonist, Antagonist, Affinity, Efficacy, Potency, Isosterism, Bioisosterism, Pharmacophore, Lead Molecule, LD₅₀, and ED₅₀.
All terms are explained in easy language with exam-focused points and short examples, so every MSc Chemistry student — especially from BAMU University and similar universities — can study quickly and confidently.
By reading this article, you will:
Understand the basic terms used in Medicinal Chemistry
Learn the difference between key drug-related concepts with simple real-life examples
Build a strong foundation for advanced topics like SAR (Structure–Activity Relationship) and Drug–Receptor Mechanism in upcoming parts
๐ Note: This is Part 1 of the chapter.
๐ Part 2 (Coming Soon): Factors Affecting Bioactivity, Theories of Drug Activity, SAR, QSAR, and Hantzsch Equation.
๐งพ These notes are prepared as per the MSc Chemistry 4th Semester syllabus of BAMU University, and are also helpful for students of other universities since the Medicinal Chemistry syllabus is quite similar everywhere.
๐Topic cover in this post:
Introduction:
Definition and introduction of following term:
- Drug & Prodrug
- Hard Drugs and Soft Drugs
- Agonists and Antagonists
- Affinity, Efficacy, and Potency
- Isosterism and Bioisosterism
- Pharmacophore
- Lead Molecule
- Lethal Dose (LD₅₀) and Effective Dose (ED₅₀)
Summary
Frequently Asked Questions (FAQs)
Defination and introduction of following terms :
1)Drug:
A drug is a chemical substance that is used to diagnose, prevent, treat, or cure diseases in humans or animals. It interacts with biological systems to produce a therapeutic effect.
Example: Paracetamol is a drug used to reduce fever and relieve pain.
Introduction to Drugs
Drugs can be natural (from plants, animals, or minerals) or synthetic (made in labs).
They work by interacting with enzymes, receptors, or DNA in the body.
The effect of a drug depends on its chemical structure, dosage, and route of administration.
Types of Drugs Based on Use:
1. Therapeutic drugs – Used for treatment (e.g., Antibiotics).
2. Preventive drugs – Used to prevent diseases (e.g., Vaccines).
3. Diagnostic drugs – Used in medical tests (e.g., Contrast agents in X-rays).
2)Prodrug
A prodrug is an inactive or less active chemical substance that gets converted into its active form inside the body through metabolism.
Explanation of Prodrugs
Prodrugs are designed to improve drug properties like absorption, distribution, and stability.
They become active only after undergoing biochemical changes (usually in the liver).
This approach helps in reducing side effects and improving drug effectiveness.
Types of Prodrugs
1. Carrier-linked prodrugs – A chemical group is attached to the drug, which gets removed in the body.
Example: Aspirin (converted into salicylic acid).
2. Bioprecursor prodrugs – Converted into the active form by enzymes or chemical reactions in the
body.
Example: Levodopa (converted into dopamine for Parkinson’s disease).
Advantages of Prodrugs
✔ Better absorption – Improves solubility and permeability.
✔ Reduced side effects – Minimizes drug toxicity.
✔ Longer action – Slow conversion provides prolonged effects.
3)Hard and soft drugs:
Drugs are divided into two types based on their metabolic susceptibility 1) hard drug 2) soft drug
Hard drug:
• These can be defined as that are biologically active and non-metabolizable in vivo
• eg enalaprilat, lisinopril. cromolyn & bisphophonates
• Hard drugs are difficult to metabolize or may not be metabolized at all.
• They stay in the body for a long time, leading to long-term effects or possible toxicity.
• These drugs are often chemically stable and undergo minimal breakdown.
• Examples: Aspirin, Amphetamines, Barbiturates, Diazepam (Valium)
Soft Drug:
These are in can be defined. as drug that produce predictable and controllable vivo metabolism to form
nontoxic product after they have shown their therapeutic role.
e-g cetyl pyridinium chlorides, soft cloramig.
• Soft drugs are easily metabolized and quickly eliminated from the body.
• Their main goal is to increase safety and reduce side effects, not to increase potency.
• Unlike prodrugs (which need to be activated in the body), soft drugs are active when taken but
break down into inactive forms after their effect.
Examples: Esmolol (short-acting beta-blocker), Remifentanil (opioid painkiller), Procaine (local
anesthetic).
4)Agonists:
An agonist is a substance (drug, hormone, or neurotransmitter) that binds to a specific receptor in the
body and activates it, producing a biological response.
Types of Agonists:
1. Full Agonists – Bind to the receptor and produce maximum response (e.g., Morphine on opioid
receptors).
2. Partial Agonists – Bind to the receptor but produce only a partial response (e.g., Buprenorphine).
3. Inverse Agonists – Bind to the receptor and reduce its activity below normal (e.g., Beta-carbolines on
GABA receptors).
4. Allosteric Agonists – Enhance receptor activity by binding to a different site (e.g., Benzodiazepines on
GABA receptors).
Examples of Agonists
Adrenaline (Agonist of adrenergic receptors – increases heart rate).
Dopamine (Agonist of dopamine receptors – affects mood and movement).
Salbutamol (Beta-2 agonist – used in asthma treatment).
Anatagonist
An antagonist is a substance (drug or molecule) that binds to a specific receptor but blocks or inhibits its
activity, preventing a biological response. Unlike agonists, antagonists do not activate the receptor;
instead, they prevent other molecules (like natural agonists) from binding and working.
Types of Antagonists:
1. Competitive Antagonists – Bind to the same receptor site as the agonist but do not activate it,
blocking the agonist's effect (e.g., Atropine blocks acetylcholine receptors).
2. Non-Competitive Antagonists – Bind to a different site on the receptor, altering its shape and
preventing activation even if an agonist is present (e.g., Ketamine blocks NMDA receptors).
3. Reversible Antagonists – Bind temporarily to the receptor and can be displaced by an agonist (e.g.,
Naloxone for opioid overdose).
4. Irreversible Antagonists – Bind permanently or for a long duration, preventing any activation (e.g.,
Phenoxybenzamine blocks alpha receptors).
5. Physiological Antagonists – Work by activating different receptors that produce opposite effects (e.g.,
Epinephrine reverses histamine effects in anaphylaxis).
Examples of Antagonists:
1. Propranolol (Beta-blocker, used to reduce heart rate).
2. Cimetidine (Histamine receptor antagonist, used for ulcers).
3. Flumazenil (Benzodiazepine antidote).
Affinity :
Affinity refers to the strength of binding between a drug (ligand) and its receptor. It determines how
easily and tightly a drug can attach to its target receptor. A drug with high affinity binds strongly, while a
drug with low affinity binds weakly and may dissociate quickly.
Factors Affecting Affinity:
1. Molecular Structure – The shape and functional groups of the drug affect how well it fits into the
receptor.
2. Non-Covalent Interactions – Hydrogen bonding, ionic interactions, van der Waals forces, and
hydrophobic interactions influence binding strength.
3. Receptor Conformation – The availability and structure of the receptor affect how well the drug can
bind.
Importance of Affinity:
1. High-affinity drugs require lower doses to achieve the desired effect.
2. Low-affinity drugs may need higher concentrations to work effectively.
3. Affinity influences drug potency and duration of action.
Example:
1. Naloxone has a higher affinity for opioid receptors than morphine, so it can displace morphine
and reverse an overdose.
2. Propranolol (beta-blocker) has a strong affinity for beta-adrenergic receptors, reducing heart
rate and blood pressure.
Efficacy
Efficacy refers to the ability of a drug to produce a maximum biological response after binding to its
receptor. It measures how well a drug activates the receptor to generate a therapeutic effect.
Key Points About Efficacy:
1. Different from Affinity – A drug can have high affinity (strong binding) but low efficacy if it does
not activate the receptor effectively.
2. Measured in Terms of Response –
The maximum effect a drug can achieve, regardless of dose.
3. Full vs. Partial Agonists –
Full agonists (e.g., morphine) have high efficacy as they fully activate receptors.
Partial agonists (e.g., buprenorphine) have moderate efficacy, producing only a partial response.
4. Antagonists Have Zero Efficacy – Since they block receptors without activating them.
Importance of Efficacy:
Determines the therapeutic potential of a drug.
Helps in drug selection—a drug with higher efficacy is often preferred for treatment.
Example:
1. Morphine has higher efficacy than codeine in pain relief.
2. Salbutamol (used for asthma) has high efficacy in relaxing airway muscles.
Potency
Potency refers to the amount of drug required to produce a specific effect. A more potent drug
produces the desired effect at a lower dose.
Key Points About Potency:
1. Different from Efficacy –
Efficacy is about how well a drug works, while potency is about how much drug is needed to produce
the effect.
drug can be highly potent but have low efficacy if it binds well but does not activate the receptor fully.
3. Measured Using ED₅₀ (Median Effective Dose) –
ED₅₀ is the dose required to achieve 50% of the maximum response.
Lower ED₅₀ = Higher Potency (less drug needed).
3. Comparison Example:
• Fentanyl is more potent than morphine because a much lower dose is needed to relieve
pain.
• Diazepam (Valium) is more potent than lorazepam, meaning a smaller dose of diazepam is
needed to achieve the same effect.
Importance of Potency:
• Helps in dose determination for treatment.
• A highly potent drug reduces the required dosage, potentially lowering side effects.
• However, high potency does not always mean better treatment if efficacy is low.
Isosterism
Isosterism refers to the similarity in physical or chemical properties between molecules or groups of
atoms due to having the same number of atoms and/or electrons. These similar groups are called
isosteres.
Types of Isosteres:
1. Classical Isosteres – Have the same number of atoms and valence electrons.
Example: -CH₃ (methyl) and -NH₂ (amino)
N₂ (Nitrogen gas) and CO (Carbon monoxide)
2. Non-Classical Isosteres – Have different numbers of atoms but similar biological properties.
Example: -OH (hydroxyl) and -NH (amine)
-SH (thiol) and -OH (hydroxyl)
Importance of Isosterism in Drug Design:
Used in medicinal chemistry to modify drugs while maintaining activity.
Helps in reducing toxicity, improving absorption, and enhancing drug stability.
Example: Sulfonamide drugs replace the carboxyl group (-COOH) with a sulfonamide (-SO₂NH₂) for
better activity.
Pharmacophores:
pharmacophore is the essential structural and chemical features of a molecule that interact with a
biological target (such as a receptor or enzyme) to produce a desired biological response.
Key Features of a Pharmacophore:
1. Hydrophobic Groups – Non-polar regions that interact with lipophilic parts of the receptor.
2. Hydrogen Bond Donors – Groups that donate hydrogen bonds (e.g., –OH, –NH₂).
3. Hydrogen Bond Acceptors – Groups that accept hydrogen bonds (e.g., =O, –N).
4. Aromatic Rings – Provide ฯ-ฯ interactions with the target site.
5. Charge Interactions – Positively or negatively charged groups that bind to oppositely charged receptor
sites.
Importance of Pharmacophores in Drug Design:
Helps identify active compounds with the desired biological effect.
Aids in modifying drug molecules to improve potency and reduce side effects.
Used in computer-aided drug design (CADD) to create new drugs with better activity.
Example:
Beta-blockers have a pharmacophore that includes a hydroxyl group (-OH) and an amine group (-NH₂),
essential for blocking ฮฒ-adrenergic receptors.
Opioids share a common pharmacophore consisting of an aromatic ring and a basic nitrogen, which
interact with opioid receptors.
Bioisosterism
Bioisosterism is the replacement of one functional group in a molecule with another that has similar
physical or chemical properties but may produce improved biological effects. This concept is widely used
in drug design to enhance activity, reduce toxicity, or improve drug properties like absorption and
metabolism.
Types of Bioisosteres:
1. Classical Bioisosteres – Atoms or groups with similar valency and size.
Example: -OH replaced by -NH₂
-H replaced by -F
-CH₃ replaced by -Cl
2. Non-Classical Bioisosteres – Groups that have different structures but provide a similar biological
effect.
Example:
Carboxyl (-COOH) replaced by Sulfonyl (-SO₂NH₂)
Benzene ring replaced by Thiophene ring
Applications of Bioisosterism in Drug Design:
• Improves drug stability (e.g., replacing ester groups to prevent hydrolysis).
• Reduces toxicity (e.g., replacing toxic functional groups).
• Enhances receptor binding (e.g., modifying drugs to fit better in the target site).
• Increases bioavailability (e.g., making drugs more soluble or better absorbed).
Example:
• Aspirin (Acetylsalicylic acid) → Bioisosteric modification → Celecoxib (COX-2 inhibitor)
• Sulfanilamide (antibacterial) → Bioisosteric modification → Furosemide (diuretic)
Lead Molecules:
A lead molecule is a chemical compound that has biological activity and serves as a starting point for
drug development. It is not yet an ideal drug but can be modified to improve its potency, selectivity, and
safety.
Characteristics of Lead Molecules:
• Shows desired biological activity (e.g., enzyme inhibition or receptor binding).
• Has a known chemical structure that allows modifications.
• Can be optimized for better efficacy and fewer side effects.
Sources of Lead Molecules:
1. Natural Products – Found in plants, microbes, marine organisms (e.g., Penicillin from fungi).
2. Synthetic Compounds – Designed in laboratories through chemical synthesis.
3. Computer-Aided Drug Design (CADD) – Virtual screening of compounds.
4. Existing Drugs – Modifying old drugs for new purposes (e.g., Thalidomide used for multiple myeloma).
5. Biological Libraries – Screening large collections of molecules for activity.
Optimization of Lead Molecules:
• To convert a lead molecule into a drug, chemists make changes to:
• Increase potency (stronger binding to target).
• Reduce toxicity (eliminate harmful effects).
• Improve bioavailability (better absorption in the body).
• Enhance selectivity (targets only disease-related molecules).
Example:
Sulfanilamide (Lead) → Modified → Sulfa drugs (antibiotics).
Morphine (Lead) → Modified → Oxycodone (painkiller).
Lethal Dose (LD₅₀) and Effective Dose (ED₅₀)
1. Lethal Dose (LD₅₀)
1. LD₅₀ (Lethal Dose 50) is the dose of a substance required to cause death in 50% of a test
population (usually animals).
2. It is used to measure the short-term toxicity or poisoning potential of a substance.
3. Expressed in mg/kg (milligrams per kilogram of body weight).a
4. Lower LD₅₀ values indicate higher toxicity.
5. Example: Cyanide has a very low LD₅₀, making it highly toxic.
2.Effective Dose (ED₅₀)
ED₅₀ (Effective Dose 50) is the dose of a drug required to produce a specified therapeutic effect in 50%
of a test population.
1. It helps determine the optimal dosage for treatment.
2. Expressed in mg/kg (milligrams per kilogram of body weight).
3. Example: If 50 mg of a painkiller relieves pain in 50% of patients, its ED₅₀ is 50 mg.
# Therapeutic Index (TI)
Therapeutic Index = Median Lethal dose / Median Effective doseTherapeutic Index
(TI) = LD₅₀ / ED₅₀
It measures drug safety—a higher TI indicates a safer drug (greater gap between toxic and
effective dose).
Example:
• Paracetamol has a high TI, meaning it is relatively safe.
• Chemotherapy drugs have a low TI, requiring careful dosing.
Summary
In this post, we studied the basic terms of Medicinal Chemistry such as drug, prodrug, hard and soft drugs, agonist, antagonist, potency, efficacy, and pharmacophore. These terms explain how drugs act, how strong they are, and how they interact with our body.
For example, when you take a painkiller like paracetamol, it acts as a drug that reduces pain by blocking certain signals — while some medicines like codeine need to change inside the body to become active, which makes them prodrugs.
By learning these key ideas, you now understand the foundation of drug design and activity, which will help you in the next part — SAR, bioactivity, and receptor mechanism.
Frequently Asked Questions (FAQs)
1. What is Medicinal Chemistry?
Medicinal Chemistry is the branch of chemistry that studies how chemical substances (drugs) interact with living systems to prevent, treat, or cure diseases. It combines organic chemistry, pharmacology, and biochemistry to design and develop safe, effective medicines.
2. What are the applications of Medicinal Chemistry?
Helps in discovering and designing new drugs.
Improves the activity and safety of existing medicines.
Studies drug–receptor interactions to understand how drugs work.
Supports pharmaceutical research and drug formulation.
3. What are the main factors that determine a drug’s effectiveness and safety?
Drug effectiveness and safety depend on two main areas:
Pharmacodynamics (PD): How the drug acts on the body — includes potency, efficacy, and mechanism of action.
Pharmacokinetics (PK): How the body acts on the drug — includes absorption, distribution, metabolism, and excretion (ADME).
4. What are the advantages of soft drugs over hard drugs?
Soft drugs are easily broken down in the body after their effect, reducing side effects.
They are safer, with lower chances of toxicity.
Their duration of action can be controlled more easily.
Example: Esmolol (soft drug) works for a short time and is safer than long-acting beta-blockers.
5. What are antibiotics?
Antibiotics are medicines used to kill or stop the growth of bacteria that cause infections.
Example: Penicillin, Amoxicillin, Tetracycline.
They do not work against viral infections like cold or flu.
6. What are antihypertensive drugs?
Antihypertensive drugs are medicines that lower high blood pressure (hypertension) and prevent heart or kidney damage.
Examples: Amlodipine, Losartan, Metoprolol.
7. Explain efficacy and potency of a drug.
Efficacy means how well a drug produces the desired effect.
Potency means how much of the drug is needed to get that effect.
๐ Example: Morphine and Codeine both relieve pain, but Morphine is more potent (needs a smaller dose) and has higher efficacy (gives stronger relief).
8. What is a prodrug?
A prodrug is an inactive substance that becomes active after metabolism inside the body.
Example: Levodopa → Dopamine.
9. What is the difference between agonist and antagonist?
Agonist: Activates receptors and produces a response.
Antagonist: Blocks receptors and prevents response.
10. What is the therapeutic index (TI)?
TI = LD₅₀ / ED₅₀.
It shows a drug’s safety margin — higher TI means safer drug.
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