1. Introduction to Medicinal Chemistry
Chapter 1 Part 1

2. What is medicinal chemistry?
The science that deals with the discovery or design of new therapeutic chemicals and the development of these chemicals into useful medicine

3. What is “medicine”? Drugs, pharmaceutics
Media distinction
A compound that interacts with a biological system, and produces a biological response (ideally desired and positive)

4. “Good” vs. “Bad” Drugs No medicine has only benefits or drawbacks
Morphine
Excellent analgesic
Addictive, tolerance
Respiratory depression
Barbiturates
Depressants, sedatives, anesthetics
Surgery
Overdoses fatal (Pearl Harbor)

5. Heroin Known clinically as Diamorphine One of the best painkillers
1898: on market
1903: withdrawn (addictive properties)
Today: still used

6. Aspirin 400 BC: Hippocrates Active component of willow bark = salicin
Chew bark of willow tree for pain (childbirth and eye infections)
Active component of willow bark = salicin

7. Cocaine South American coca bush Isolated 1880’s Addiction: Freud
Plant used as a stimulant, mystical/religious reasons
Isolated 1880’s
Anesthetic in dentistry
Addiction: Freud
Used for depression; other drug addiction
Drug development based on structure
Procaine (Novocain)

8. Everyday drugs Still produce a response; many are addictive Caffeine
Sugar
Nicotine
Alcohol
Food additives
Vitamins
Herbs
Basil: 50 potential carcinogens
Cultural aspects

9. “Good” vs. “Bad” Drugs Depends on:
Dosage
Almost anything in excess will be toxic
Chronic exposure
Measure of safety of drug = therapeutic index

10. Therapeutic index
Measure of a drug’s beneficial effects at low dose vs. harmful effects at high dose
Comparison of dose levels which lead to toxic effects to dose levels which lead to maximum therapeutic effects
High therapeutic index = large margin of safety
Marijuana = 1000
Alcohol = 10
Does not take chronic use into account

11. Classification of drugs
Four main groups (overlap)
1. By pharmacological effects
Analgesics, anti-asthmatics, antipsychotics, etc.
Large and varied assortment of drugs
Many mechanisms of action
2. By chemical structure
Penicillins, steroids
Common skeleton
Functions may be similar or different

12. Classification of drugs
3. By target system
Antihistamines
Affect a target system (synthesis, release, receptor)
Variety of structures due to large number of stages in system
4. By target molecule or site of action on target
Very specific classification
Expect structural similarity and common mechanism
Easy to classify compounds too narrowly and miss possible positive side effects (new uses for the compound)
Zyban
Viagra