Download Chemistry 4205

Introduction to Medicinal Chemistry
Chapter 1 Part 1
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
What is “medicine”?
 Drugs, pharmaceutics
 Media distinction
 A compound that interacts with a biological system, and
produces a biological response (ideally desired and positive)
“Good” vs. “Bad” Drugs
 No medicine has only benefits or drawbacks
 Morphine
HO
 Excellent analgesic
 Addictive, tolerance
 Respiratory depression
O
N
 Barbiturates
 Depressants, sedatives, anesthetics
 Surgery
 Overdoses fatal (Pearl Harbor)
H
HO
CH3
Heroin
 Known clinically as Diamorphine
 One of the best painkillers
 1898: on market
 1903: withdrawn (addictive properties)
 Today: still used
H3C
O
C
O
O
N
O
H
C
H3C
O
CH3
Aspirin
 400 BC: Hippocrates
 Chew bark of willow tree for pain (childbirth and eye infections)
 Active component of willow bark = salicin
O
O
OH
glucose
O
O
OH
1. Hydrolysis
2. Oxidation
OH
Ac2O
Ac
(1883: Bayer)
OH
Salisylic acid
- more effective
- no bitter taste
- gastric bleeding
O
Acetylsalicylic acid (aspirin)
- less irritating
- ester hydrolyzes to active drug
Cocaine
O
O
 South American coca bush
 Plant used as a stimulant, mystical/religious
O
O
reasons
N
 Isolated 1880’s
 Anesthetic in dentistry
 Addiction: Freud
 Used for depression; other drug addiction
 Drug development based on structure
 Procaine (Novocain)
O
N
O
NH2
Everyday drugs
 Still produce a response; many are addictive
 Caffeine
 Sugar
 Nicotine
 Alcohol
 Food additives
 Vitamins
 Herbs
 Basil: 50 potential carcinogens
 Cultural aspects
“Good” vs. “Bad” Drugs
 Depends on:
 Dosage
 Almost anything in excess will be toxic
 Chronic exposure
 Measure of safety of drug = therapeutic index
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
Classification of drugs

Four main groups (overlap)
1. By pharmacological effects
2.

Analgesics, anti-asthmatics, antipsychotics, etc.

Large and varied assortment of drugs

Many mechanisms of action
By chemical structure

Penicillins, steroids

Common skeleton

Functions may be similar or different
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
