chapter 1 part 1 introduction to medicinal chemistry

Post on 29-Dec-2015

351 Views

Category:

Documents

13 Downloads

Preview:

Click to see full reader

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Known clinically as DiamorphineOne of the best painkillers1898: on market1903: withdrawn (addictive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

top related