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 Excellent analgesic Addictive, tolerance Respiratory depression Barbiturates Depressants, sedatives, anesthetics Surgery Overdoses fatal (Pearl Harbor)

Heroin Known clinically as Diamorphine One of the best painkillers 1898: on market 1903: withdrawn (addictive properties) Today: still used

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

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)

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 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 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