chapter 1 part 1 introduction to medicinal chemistry
TRANSCRIPT
Chapter 1 Part 1
Introduction to Medicinal Chemistry
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
HO
O
HO
H
N
CH3
No medicine has only benefits or drawbacks
MorphineExcellent analgesicAddictive, toleranceRespiratory depression
BarbituratesDepressants, sedatives, anestheticsSurgeryOverdoses fatal (Pearl Harbor)
Heroin
O
O
O
H
N
CH3C
H3C
O
C
O
H3C
Known clinically as DiamorphineOne of the best painkillers1898: on market1903: withdrawn (addictive
properties)Today: still used
Aspirin400 BC: Hippocrates
Chew bark of willow tree for pain (childbirth and eye infections)
Active component of willow bark = salicin
OH
O
OH
O
O
OH
O
O
OH1. Hydrolysis
2. Oxidationglucose (1883: Bayer)
Ac2O
Ac
Salisylic acid - more effective - no bitter taste - gastric bleeding
Acetylsalicylic acid (aspirin) - less irritating - ester hydrolyzes to active drug
Cocaine
N
O O
OO
NH2
O
N
O
South American coca bushPlant used as a stimulant,
mystical/religious reasons
Isolated 1880’sAnesthetic in dentistry
Addiction: FreudUsed for depression; other drug
addiction
Drug development based on structureProcaine (Novocain)
Everyday drugsStill produce a response; many are
addictiveCaffeineSugarNicotineAlcoholFood additivesVitaminsHerbs
Basil: 50 potential carcinogensCultural aspects
“Good” vs. “Bad” DrugsDepends on:
DosageAlmost 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 safetyMarijuana = 1000Alcohol = 10Does not take chronic use into account
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
Classification of drugs3. 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