Lecture 1 Concept Notes Flashcards
SAR
Structure activity relationship:
How the structure of the drug affects how the drug functions in the body
MOA
Mechanism of Action
How the drug reacts with targets in the body on a molecular level
ADME
Absorption, distribution, metabolism and excretion
can sometimes also include toxicity
Where is aspirin derived from?
Willow tree bark contains salicylic acid which is one of the precursors for aspirin
Where is morphine derived from?
From opium poppy, a plant
How to define a good or a bad drug?
Subjective. Can depend on how the drug interacts and side effects in the body. Too much of any drug can be harmful
Medicinal Chemistry goal
improve drugs to the best of their ability
Therapeutic Index
The ratio between the therapeutic effect & the toxicity of the drug.
T/F:
A small TI is good
False.
We want the therapeutic index to be as large as possible. This means we can give multiple or higher doses of a drug before the drug starts to have toxic effects on the body.
Warfarin, small therapeutic index. Explain
If another dose is given of warfarin, it increases the chance of the drug causing issues in the body. There is unwanted adverse effects with a smaller dose of warfarin.
Pencillin, large thereputic index
Multiple doses or higher doses of penicillin are okay, and will not cause unwanted adverse effects in the body
Name two ways a drug target can be validated
Gene Knockout, and RNAI (RNA interference )
Explain Gene Knockout
When a gene is removed from expressing to see how a disease progresses without it.
RNA interference
reduces expression through RNA molecules and gives insights as to how disease progression occurs without that gene
Receptors Validation
Validates the relationship between the receptor and the drug
Enzyme Validation
Validates how enzymes interact with the drug
Ion channel validation
Validates how ion channels interact with the drug
protein-protien interaction
interactions between proteins and the drug
Example of a biological target: Lipitor (dont need to know but to explain the concept)
CoA receptors
Natural Products
fully derived from a natural product like a fungi, bacteria, plants, etc.
Name three drugs that are natural products
Erythromycin A
Morphine
Lovastatin
Natural product analogs
Semi-synthetic approach
Drug is edited from a natural product and some functional groups change
Examples of natural product analogs & what theyre synthesized from
Heroin and Oxycodone –> from Morphine
Simvastatin –> Lovastatin
Telitrhomycin –> Erythromycin
Example of Natural product inspired agents
Methadone & Procaine
Natural product inspired agents
Inspired from a natural product, but changes in significant ways
Synthetic drugs (based on rational design)
Created rationally
Ex- finding a substrate that fits into an enzyme and creating a drug that looks like the substrate that wont be metabolized, but rather prevent the enzyme from working
Example of a synthetic drug
Captopril
Synthetic drug
Fully synthetically made
HTS (high throughput screening)
Screens hundreds of thousands of compounds until a hit is found
Examples of synthetic drugs
Clopidogrel (Plavix) or Imatinib (Gleevec)
Serendipity in drug discovery
Drugs that are discovered by accident, or for another indication.
Examples of serendipity
Penicillin or Viagra
how was penicillin discovered
It was observed that penicillin inhibits bacterial growth on a mold plate
what was viagra initially used for
Viagra was initially use for chest pains and found to be useful for erectile dysfunction
