Introduction to Medicinal Chemistry

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Introduction to Medicinal Chemistry

• Chapter 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

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What is medicine?

• Drugs, pharmaceutics
• Media distinction
• A compound that interacts with a biological
  system, and produces a biological response
  (ideally desired and positive)

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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

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• 1903 withdrawn (addictive properties)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

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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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Medicinal Chemistry

• Under what conditions are drugs good, and what
  do they do to the body?
• Curare/Tubocurarine

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Classification of drugs

• Four main groups (overlap)
• 1. By biological effect
• Analgesics, anti-asthmatics, antipsychotics, etc.
• Large and varied assortment of drugs
• Many mechanisms of action
• 2. By chemical structure
• Penicillins, opiates
• Common skeleton
• Functions 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 site of action
• Anticholinesterases (inhibit acetylcholinesterase
  in CNS)
• Target enzyme or receptor
• Usually common mechanism

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Controlled Substances Act

• Drug scheduling (I V)
• Potential for abuse, safety, dependence
• Currently accepted for medical use
• DEA list of scheduled drugs

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History of Medicinal Chemistry

• Studied/practiced for thousands of years
• Medicine men/witch doctors
• Roots, plants, trees, berries, herbs
• Often placebos
• Leeches and maggots
• Last 150 years Mechanism of reaction/response
• 1909 first chemotherapy (Ehrlich)
• Salvarsan (compound 606) for syphilis
• Aside naming drugs (see App.6)
• Later replaced with penicillin (1940s)
• 2005 Structure determination

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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)