This document provides an overview of key concepts in medicinal chemistry. It defines medicinal chemistry as concerning the discovery, development, and interpretation of biologically active compounds at the molecular level. It then discusses the relationships between organic chemistry, medicinal chemistry, and pharmaceutical chemistry. The rest of the document covers topics like drug nomenclature, classification, pharmacology principles of drug action, toxicology, and assays.

1. Prepared By
Dr. Krishnaswamy. G
Faculty
DOS & R in Organic Chemistry
Tumkur University
Tumakuru
For
I M.Sc., I Semester
DOS & R in Organic Chemistry
Tumkur University
Tumakuru
MEDICINAL CHEMISTRY

2. MEDICINAL CHEMISTRY
Chemical compounds
which shows
Physiological /
biological /
therapeutic action
Medicine or Drug
Physiological /
biological /
therapeutic action of
any compounds
depends on structure
and its arrangements
‘Medicinal chemistry concerns the discovery, the development,
the identification and the interpretation of the mode of action of biologically
active compounds at the molecular level.
IUPAC Definition

3. New
Molecules
Biological
Characterization
Chemical
Characterization
Structure
property
relationship
Organic Chemistry
(Concerns Design &
Synthesis)
- Natural Products
- New synthetic approaches
Medicinal Chemistry
(Concerns Molecules)
- Identification
- Optimization
Pharmaceutical Chemistry
(Concerns Products)
- Analysis
-Bioavailability
-- Bioequivalence
- Physicochemical properties
-Conformation
-- Stereochemistry
- ADME
-Toxicity
- Molecular Modeling
- QSAR

4. Name The word Drug derived from Greek
“Pharmacon” means drug
The word Medicine derived from Latin
“Medicus” means healing
Definition Substances which can change the
physical and physiological state -
Drug
Substances that have definite form and
therapeutic use for treatment -
Medicine
Drug is a substance which cures the
disease but is habit forming, causes
addiction and has serious side
effects.
Medicine is a chemical substance which
cures the disease, has negligible toxicity
and does not cause any addiction
Amount Drug does not have any definite form
and dose.
Medicine has definite form and dose.
Relation with API Drug = API (Active Pharmaceutical
Ingredient)
Medicine = API ± Excipients
Potency Drugs are active potent compound. Medicines are administrative form of
drug.
Source Plants, animals, microorganisms,
synthetic, minerals
Drug and excipient.
Comparison All drugs are not medicines All medicines are drugs
Selectivity Non selective Selective
Example Paracetamol Napa (paracetamol) 500 mg tablet
Difference between Drug and Medicine

5. Disintegration of
dosage form.
Dissolution of
active substance
Absorption
Distribution
Metabolism
Excretion
Drug-receptor
interaction in
target tissue
Pharmaceutical Phase
Pharmacokinetic Phase
Pharmacodynamic Phase
Drug available
for absorption
Drug available
for action
Three Phases of Drug action
DOSE

6. Pharmacology Pharmacon logos
+
=
Drug To study
Study of Drug, Drugs effect on body and Body response for the Drug.
Pharmacology Pharmacokinetic Pharmacodynamics
+
=

7. The purpose of studying pharmcokinetics and
pharmacodynamics is to understand the drug action,
therapy, design, development and evaluation.
Pharmacokinetics is what the Body Does To The Drug
like how the drug is absorbed, Distributed,
Metabolized and Excreted by the body – Drug
Disposition.
Pharmacodynamics is what the Drug Does To The
Body which may be the therapeutic effect or the
adverse side effect – Drug Action.

8. Nomenclature of Drugs
Drugs have three or more names.
These names are the following:
a) Code number or code designation;
b) Chemical name;
c) Proprietary, trivial, brand or trade name;
d) Nonproprietary, generic, official, or common name; and
e) Synonym and other names.

9. The code number is usually formed with the initials of the laboratory or the
chemist or the research team that prepared or tested the drug the first time,
following by a number. It does not identify the chemical nature or structure
of the drug. Its use is discontinued as soon as an adequate name is chosen.
The chemical name is the only one that describes unambiguously the
chemical structure of a drug, identifying it fully and exactly. It is given
according to rules of nomenclature of chemical compounds. Since the
chemical name is sometimes very elaborate, it is not suitable for routine
usage.
a) Code number or code designation;
b) Chemical name;

10. The proprietary name is the individual name selected and used by
manufacturers. If a drug is manufactured by more than one company
c) Proprietary, trivial, brand or trade name;
The nonproprietary name refers to the common, established name by
which a drug is known as an isolated substance, irrespective of its
manufacturer. It is chosen by official agencies, such as the U.S. Adopted
Names (USAN) Council, the American Pharmaceutical Association, and
other.
d) Nonproprietary, generic, official, or common name;

11. Synonyms are names given by different manufacturers to the same drug or
old nonproprietary names. Some drugs may have several names.
e) Synonym and other names.
EXAMPLE: Paracetamol
Chemical Name: N-(4-hydroxyphenyl)acetamide
Non Proprietary Name:
British Approved Name (BAN): Paracetamol
United States Adopted Name (USAN): Acetaminophen
Proprietary Name:
Panadol, Calpol, Adol
Official Name:
Acetaminophen

12. Classification of Drugs
Drugs can be classified according to various criteria. Usually,
they are classified according to
a) Chemical Nature,
b) Source,
c) Target organ / Site of Action,
d) Mechanism of action and
e) Therapeutic use.

13. Classification based on Chemical Nature
Inorganic Drugs Organic Drugs
Metals and their salts
(FeSO4, MgSO4)
Non metals includes
sulphur
Alkaloids
(Atropine, Morphine)
Proteins
(Insulin, Oxytocin)
Esters, Amide, Alcohol

14. Classification based on Source
Plants (Morphine,
Atropine)
Animals (Insulin)
Microorganism
(Pencillin)
Mineral
(Sodium chloride)
Sulphoamides Amoxicillin, Ampicillin
Natural source Synthetic source Semi Synthetic source

15. Classification based on Target organ / Site of Action
Drug acting on CNS (Diazepam)
Drug acting on Respiratory System (Bromhexamine)
Drug acting on GIT (Omeprazole)
Drug acting on Urinary system (Magnesium
sulphate)
Drug acting on Reproductive System (Oxytocin)

16. Classification based on Mechanism of action
Inhibitor of Bacterial Cell wall synthesis (Pencillin)
Inhibitor of Bacterial protein synthesis (Tetracycline)
Calcium Channel Blocker (Nifedipine)

17. Classification based on Therapeutic use
Antimicrobials – Drugs which are used to cure diseases caused by microbes
or microorganisms such as bacteria, fungi, virus etc.
Anti-infectives
Antibacterials – Drugs which are used to cure diseases caused by bacteria.
Antifungals – Drugs which are used to cure diseases caused by fungi.
HO
NH2 H
N
O N
S
O
OH
O
Chemical structure of Amoxicillin
Chemical structure of Fluconazole

18. Antitubercular - Drug used to treat tuberculosis caused by Mycobacterium
tuberculosis.
N
H
N
O
NH2 Chemical structure of Isoniazid
Antivirals - Drug used to prevent and treat HIV/AIDS .
Chemical structure of Abacavir

19. Antibiotics – Chemical substance which in low concentration either kill or
inhibit the growth of microorganisms intervening in their metabolic process.
They are classified into two classes
(1) Bactericidal which is used to kill bacteria
(2) Bacteriostatic which is used to inhibit the growth of bacteria.
N
N
O
F
OH
O
HN
Chemical structure of Ciprofloxacin

20. Analgesics – Drugs which reduce pain without causing impairment of consciousness,
mental confusion of disorder of the nervous system.
These are classified into following two categories
Non-narcotic Analgesics: Aspirin and paracetamol are the most important examples
of non-addictive analgesics.
Narcotic Analgesics: Drugs which when administered in small doses relieve pain and
produce sleep are called narcotics. However, in large doses, they produce laziness,
coma and may ultimately cause death.
Central Nervous System Drugs

21. Antiseptics and Disinfectants
The chemical substances which prevent the growth of micro-organisms or may
even kill them when applied to living tissues like skin, are called Antiseptic.
Examples of Antiseptic:
Dettol: It is a mixture of chloroxylenol and terpineol in a suitable solvent. It is widely
used for cuts, wounds etc.
Iodine: It is used as a tincture of iodine(a 2-3% sol. of iodine in alcohol and water)

22. The chemical substances which are used to kill harmful micro-organisms but are
not safe to be applied to the living tissues are called Disinfectants.
Examples of Disinfectants:
1% solution of phenol is a disinfectant.
Example: A 0.2% solution of phenol is used as an antiseptic but 1% solution of
phenol is used as a disinfectants.

23. Antacids: Excess production of Hydrochloric acid in our stomach cause
irritation and pain. Sometimes in severe cases, ulcers can also be produced
in the stomach. Hence, ‘the substances which neutralize the excess acid
and raise the pH to an appropriate level in stomach are called Antacids’.
Examples: Sodium Bicarbonate, magnesium hydroxide etc.
Structure of drug Cimetidine
The secretion of pepsin and hydrochloric acid is stimulated by Histamine.
Therefore, the drug cimetidine was developed to stop the interaction of histamine
with the receptors that are present in the stomach wall. As a result, less
hydrochloric acid is released and the problem of hyperacidity can be solved.

24. Anti-cancer drugs also called antineoplastic drug, any drug that is effective in the
treatment of malignant, or cancerous, disease.
Cis platin (Cis-dichlorodiammineplatinum(II)) is alkylating agent binds to DNA and
leads to cancer cell death
Pt
NH3
NH3
Cl
Cl
Chemical structure of Cisplatin
N
H
NH
F
O
O
Chemical structure of 5-Fluorouracil
Antineoplastic agent used to treat various kinds of cancer namely colorectal,
breast, stomach, pancreatic and cervical.

25. OH
O
Chemical structure of Ibuprufen
Anti-inflammatory drugs also known as Nonsteroidal anti-
inflammatory drugs (NSAIDs) block the COX enzymes and reduce prostaglandins
throughout the body. As a consequence, ongoing inflammation, pain, and fever
are reduced.
Tranquilizers also known as antidepressant drugs used for the treatment of
stress, fatigue, mild and severe mental diseases.
Noradrenaline is one of the several neurotransmitters which play an important
role in mood change. If the level of noradrenaline in the body is low, then the
message transfer process becomes slow and the person suffers depression.
Chemical structure of Iproniazid

26. Diuretics also called water pills medication designed to increase the amount of
water and salt expelled from the body as urine.
The most common condition treated with diuretics is high blood pressure.
The drugs reduce the amount of fluid in your blood vessels, and this helps
lower your blood pressure.
Antimalarial drugs used to treat malaria caused by Plasmodium species.
Chemical structure of Chloroquine
Chemical structure of Furosemide

27. Drug can produce toxic / adverse effect in addition to
therapeutic / pharmacological effect.
No drug is free from side effects
With some drugs toxic effect may be minor while with certain
drugs there may be serious problems.
Toxicology: Branch of Science deals with the amount of an
agent that causes an adverse action in living system.
In order to get an idea about the safety of drugs therapeutic
index can be used.

28. THERAPEUTIC INDEX
THERAPEUTIC INDEX =
Dosage of a drug that cause a toxic / lethal effect
Dosage of a drug that causes therapeutic effect
THERAPEUTIC INDEX =
LD 50
ED 50
THERAPEUTIC INDEX =
TD 50
ED 50
Animals Humans
DOSE: Amount of drug administered

29. Median Lethal Dose(LD 50)
Dose which kills 50 % or half the population of animal
tested.
Median Toxic Dose(TD 50)
Dose which kills 50 % or half the population of humans
tested.
Dose which produce the desired response in 50 % or
half the population of animal / humans tested.
Median Effective Dose(ED 50)

30. Higher the therapeutic index = Safer is the drug
Therapeutic index (> 10) = Safe drug
Therapeutic index (4 – 10) = Relatively safe
Therapeutic index (2 – 4) = Toxic
Therapeutic index (< 2) = Highly Toxic

31. THERAPEUTIC INDEX
ED 50 LD / TD 50
%
Response
%
Death
50
100
50
100
THERAPEUTIC EFFECT
TOXIC EFFECT
Dose (mg/kg)
Drug Safety - THERAPEUTIC INDEX

32. Half Maximal Effective Concentration (EC 50)
The drug concentration producing 50% of a maximal
effect
Example: Administering a 1000 mg dose of acetaminophen
(ED50) orally will result in a plasma concentration of 15 mg/ml
(EC50), which produces effective pain relief in 50% of adult
patients.

33. Half Maximal Inhibitory Concentration (IC 50)
Drug needed to inhibit a given biological process or biological
component by 50%.
-log (IC 50)
pIC 50 =
(IC 50) values can be expressed in terms of pIC 50

34. An assay is a process of analyzing
a substance to determine its composition or quality
The biological or pharmacological potency of drug
1) Chemical assay – Chemical methods are employed for
estimation of the concentration.
Qualitative: Extraction, Distillation, Precipitation and other
physicochemical methods.
Quantitative: Volume or Weight
Types of assay

35. 2) Bio assay – an analytical method to determine concentration
or potency of a substance by its effect on living cells or tissues.
Chemical assay
More Precise
Less time consuming
Active constituent and
structure fully established
Less sensitive
Bio assay
 Less Precise
More time consuming
Active constituent and
structure not known
More sensitive

37. Immuno assay – an analytical method which uses antibodies as
reagent to quantitate or detect specific analyte.
Antibody and antigen complexes used as means of measurable
results.

38. Metabolites Antimetabolites
Definition Any substances produced by
or taking part in a metabolic
reaction Metabolites
Any substances (medicine) that
compete with or inhibits the
normal metabolic process
often by acting analogue of an
essential metabolite –
Antimetabolites
Example Uracil 5-Fluorouracil
Structure
Role Thymidylate synthetase (TS)
enzyme for DNA synthesis
Inhibits Thymidylate synthetase
(TS) enzyme for DNA synthesis

39. ↓ dTMP → ↓ DNA and ↓ protein synthesis

40. PHARMACOPHORE
“An ensemble of steric and electronic features that is necessary
to ensure the optimal supramolecular interaction with a
specific biological target and to trigger or block its biological
response”.

41. PHARMACOPHORE UNITS

42. In Drug Design the term pharmacophore refers to a set of
features that is common to a series of active molecules.
Hydrogen bond donors and acceptors, positively and
negatively charged group and hydrophobic region are typical
features. Such features are referred as pharmacophoric groups