Organic medicinals introduction

1. 1
INTRODUCTION TO
MEDICINAL CHEMISTRY

3. Define Medicinal Chemistry
Relate with other subject courses
List down its goals
Describe the Roles of a medicinal chemist
Classification drugs
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OBJECTIVES:

4. Medicinal Chemistry
is the science, which deals with the discovery
and design of new and better therapeutic
chemicals and development of these chemicals
into new medicines and drugs.
Drug Discovery
How they are discovered
How they act
How are they developed into clinical trials
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DEFINITION

5. It is an interdisciplinary research area
incorporating different branches of
chemistry and biology in the research for
better and new drugs.
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MEDICINAL CHEMISTRY

6. To provide an understanding of the principles
of medicinal chemistry:
Consider the physicochemical properties
Their mechanism of action
Drugs metabolism & metabolites activity
Stereochemistry in Drug design
Methods used to determine what “space” a drug
occupies.
GOALS

7. 1. Make new compounds
2. Determine the effect of the drug on biological
processes
3. Alter the structure of the compound
for optimum effect and minimum
side effects
4. Study uptake, distribution, metabolism
and excretion of drugs.
ROLE OF MEDICINAL CHEMIST

8. Is devoted to the discovery & development of
NEW agents for treating diseases.
Development of organic compounds has grown
beyond traditional methods.
BIOTECHNOLOGY
Uses Recombinant DNA
Site-directed mutagenesis
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DISCIPLINE

9. Pure organic compounds are the chief source
of agents for the cure, mitigation or the
prevention of disease.
 These remedial agents could be classified
according to their origin:
• Natural compounds
• Synthesis compounds.
• Semi-synthesis compounds
DRUG

10. • Natural compounds: materials obtained from both
plant and animal, e.g. vitamins, hormones, amino acids,
antibiotics, alkaloids, glycosides…. etc.).
• Synthetic compounds: either pure synthesis or
synthesis naturally occurring compounds (e.g. morphine,
atropine, steroids and cocaine) to reduce their cost.
• Semi-synthetic compounds: Some compounds either
can not be purely synthesized or can not be isolated from
natural sources in low cost. Therefore, the natural
intermediate of such drugs could be used for the
synthesis of a desired product (e.g. semi synthetic
penicillins).
CLASSIFICATION ACCORDING TO ORIGIN

11. I. Chemotherapeutic agents:
Those drugs which are used to fight malignant
cells/tissues (e.g. sulphonamides, antibiotics,
antimalarial agents, antiviral, anticancer etc.).
II. Pharmacodynamic agents:
Drugs that act on the various physiological functions
of the body (e.g. general anaesthetic, hypnotic and
sedatives, analgesic etc.).
GENERAL CLASSIFICATION ACCORDING
TO MEDICINAL USES

12. 1. Infectious diseases: Born (transmitted) from person to
person by outside agents, bacteria (pneumonia,
salmonella), viruses (common cold, AIDS), fungi (thrush,
athletes foot), parasites (malaria)
2. Non-infectious diseases: disorders of the human body
caused by genetic malfunction, environmental factors,
stress, old age etc. (e.g. diabetes, heart disease,
Haemophilia, asthma, mental illness, stomach ulcers,
arthritis).
3. Non-diseases: alleviation of pain (analgesic), prevention
of pregnancy (contraception) , anesthesia.
CLASSIFICATION ACCORDING TO TYPES
OF DISEASES TREATED

13. TO BE CONTINUED….

14. A. ACCORDING TO DISEASE IT CAN TREAT
Write “ID” for INFECTIOUS DISEASE
Write “NID” for NON-INFECTIOUS
Write “ND” for NON-DISEASE
B. ACCORDING TO ITS MEDICINAL USE
Write “CT” for CHEMOTHERAPEUTIC
Write “PD” for PHRAMACODYNAMIC
C. CURE or PREVENT?
EACH NUMBER HAS 3 ANSWERS… EXAMPLE:
1. ID – CT - CURE
2. NI – PD - PREVENT
SHORT QUIZ

15. 1.Tuberculosis and Bacille Calmette-Guerin
2.Rabies and Verorab
3.Tuberculosis and Isoniazid
4.Rabies and Imogam
5.Pregnancy and Diane Pills
6.Breast Cancer and Xeloda
7.Pain and Ponstan
8.Diabetes and Diamicron
9.Sun Burn and Nivea Sunblock
10. Hypertension and Diovan
SHORT QUIZ

16.  USE OF NATURAL EXTRACTS FOR MEDICINAL PURPOSES WERE
THE START.
 1900, 1/3 OF ALL DEATHS IN THE US WERE FROM 3 GENERAL
CAUSES THAT ARE RARE TODAY BECAUSE THEY ARE
PREVENTABLE LIKE PNEUMONIA, TUBERCULOSIS, DIARRHEA
 THE RISE OF SYNTHETIC ORGANIC CHEMISTRY OR THE NON-
NATURAL DRUG CANDIDATES.
 THE FIRST NOTABLE PERIOD WAS IN 19TH CENTURY FROM THE
SERENDIPITY FINDINGS OF MEDICAL CHEMISTS.
 THE 2ND PERIOD WAS ON EARLY 2OTH CENTURY, ANTIBIOTIC
DISCOVERY.
 THE DISCOVERY OF THE MIRACLE DRUG: PENICILLINS IN
WORLD WAR II. Alexander Fleming…
Howard Walter Florey / Ernst Chain / Norman Heatly
DRUG DISCOVERY

17.  VIA RANDOM SCREENING: DISCOVERY OF SULFONAMIDE
 FROM TARGETED DEDICATED SCREENING AND RATIONAL DRUG
DESIGN-INVOLVEMENT OF QSAR (Quantitative structure–
activity relationship)
 VIA DRUG METABOLISM STUDIES: METABOLITE CAN HAVE
OTHER USES, TERFENADINE AND FEXOFENADINE.
DRUG DISCOVERY

18.  PLANTS
 ANIMAL
 MINERAL/EARTH
 MICROBIOLOGICAL
 SEMI SYNTHETIC
 RECOMBINANT DNA TECHNOLOGY
REVIEW ON DIFFERENT DRUG SOURCES

19.  REFINEMENT OF LEAD COMPOUNDS:
 DETERMINATION OF THE PHARMACOPHORE
 ALTERATIONS IN ALKYL CHAINS
 FUNCTIONAL GROUP MODIFICATION
 BIOISOTERISM
STRUCTURAL MODIFICATIONS OF DRUGS

20.  DISCOVERY:
 IDENTIFICATION OF NEW, OR PREVIOUSLY UNDISCOVERED
BIOLOGICALLY ACTIVE COMPOUND CALLED “HITS”.
 CHEMICAL OR FUNCTIONAL GROUP MODIFICATIONS TO
IMPROVE “HIT” TO “LEAD”.
 LEAD COMPOUND SHOULD NOW POSSESS CHEMICAL
STRUCTURE, MECHANISM OF ACTION, FUNCTIONAL GROUPS
RECOGNIZED BY THE RECEPTOR/ACTIVE SITES.
 “LEAD OPTIMIZATION” MODIFICATION OF FUNCTIONAL GROUP
TO IMPROVE ITS ACTION.
 FINAL STEP IS TO MAKE IT DRUG CANDIDATE FOR CLINICAL
TRIAL.
DRUG DEVELOPMENT PROCESS

21. DISCOVERY
LEAD
OPTIMIZATION
TOXICOLOGY
CLINICAL
DEVELOPMENT

22.  Let’s make a change on an existing compounds or synthesize
a new structure and see what happens.
 Drugs: power cost
DRUG DESIGN STRATEGIES

23. Given a budget, what medicine are
you dreaming to make? and can you
visualize its physical and chemical
properties? (Note: you can decide your
own generic name or you can improve
a market-ready medicine by removing
its negative properties.
ASSIGNMENT: BE A MEDICINAL CHEMIST

24. Early drug design started with elucidation of the structure of
the natural product, followed by selective changes in the
molecule.
The latter was done for many reasons, including:
1. the reduction of an undesirable pharmacologic response
(side effects);
2. obtaining a better pharmacokinetic response;
3. altering the drug’s metabolism;
4. securing a more plentiful, less costly supply; and
producing a competing product.

25. The ideal drug molecule will
show favorable binding
characteristics to the receptor. At
the same time the drug will be
expected to dissociate from the
receptor and re-enter systemic
circulation to be excreted.

26. A WORD