Drug Discovery 1 Flashcards
(40 cards)
What is a lead compound?
The improved molecule via physicochemical, pharmacologic, toxicologic, and pharmacokinetic modifications of a “hit”
What might biologists discover?
A novel biological target
- an enzyme
- a receptor
What is a drug?
A molecule that can be designed and synthesised
What are the two classes of drugs?
Chemical drugs
Biological drugs
Describe chemical drugs.
Chemical Drugs
Range from simple inorganic salts to complex organic molecules.
Organic drug molecules often referred to as small molecules these are ‘drug-like’ organic compounds with a molecular weight approximately < 500.
When discovered, referred to as a ‘New Chemical Entity’ (NCE).
Describe biological drugs.
Biological Drugs (“Biologics”).
Also known as large molecule drugs. Usually proteins such as peptides or antibodies (but could be a nucleic acid, e.g. gene therapy).
When discovered, referred to as a ‘New Biological Entity’ (NBE).
What is a small organic drug referred to once discovered?
A New Chemical Entity (NCE)
What is a large molecule drug referred to once discovered
A New Biological Entity (NBE)
What are New Chemical Entities and New Biological Entities known as when considered together ?
New Molecular Entities (NMEs)
Where do novel Small Molecules come from?
Natural sources or derived from nature Derived from endogenous compounds - biochemical Synthetic drugs - derived from screening or rational medicinal chemistry Serendipity 'Me too' In silico drug design - molecular modelling
Why are small lead compounds often not suitable drug molecules?
Do not have suitable properties to use clinically
- poor aqueous solubility
- low activity
Usually require optimisation
Historically, what was the only source of medicines?
Nature
- herbal medicine
- Chinese medicine
- minerals
- mercury
- arsenic
What is a Natural Product?
A discrete compound produced by a living organism
- very valuable to medicine
Give examples of medicinal natural products that have been derived from plants
Paclitaxel- breast and ovarian cancer.
Isolated from bark of the yew tree.
Quinine- malaria.
Isolated from bark of cinchona tree
Digoxin - Digoxin, heart failure, arrhythmias.
Leaves of the Foxglove.
Morphine- analgesic.
Contained within resin from poppy seeds.
Give an example of a drug that is derived from a natural product
Aspirin
- willow bark used from 400BC to relieve fever
How is salicin converted into aspirin?
Hydrolysis removes sugar group
Oxidation -> salicylic acid
Acetylation -> aspirin
How is morphine converted to diamorphine?
Acetylation
Why might biochemicals or natural ligands within the body not make good lead compounds prior to analogue synthesis?
Natural ligand may
- have undesirable duration of action
- be excreted or metabolised too quickly
- be chemically unstable
Why are small lead compounds often not suitable drug molecules?
Do not have suitable properties to use clinically
- poor aqueous solubility
- low activity
Usually require optimisation
Why might biochemicals or natural ligands within the body make good lead compounds after analogue synthesis?
Natural ligand beforehand may
- have undesirable duration of action
- be excreted or metabolised too quickly
- be chemically unstable
What does changing the structure of an endogenous lead compound allow?
Determination of structure activity relationships (SAR)
Why must analogues of natural ligands retain their core structures?
Allow binding to the biological target
What is methotrexate?
Anti-proliferative drug
- blocks the effect of folic acid
- essential for cell growth
Discovered from a collection of compounds all with structural similarities to folic acid
Which synthetic derived drugs were noted for their anti-bacterial properties in the early 1900s?
azo dyes
