Chapter 1 Part 1

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Introduction to Medicinal Chemistry

• Chapter 1 Part 1

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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)

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Heroin

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• 1903 withdrawn (addictive properties)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

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Aspirin

• 400 BC Hippocrates
• Chew bark of willow tree for pain (childbirth and
  eye infections)
• Active component of willow bark salicin

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Cocaine

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

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Everyday drugs

• Still produce a response many are addictive
• Caffeine
• Sugar
• Nicotine
• Alcohol
• Food additives
• Vitamins
• Herbs
• Basil 50 potential carcinogens
• Cultural aspects

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Good vs. Bad Drugs

• Depends on
• Dosage
• Almost anything in excess will be toxic
• Chronic exposure
• Measure of safety of drug therapeutic index

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Therapeutic index

• Measure of a drugs 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

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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

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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