Lecture 1 Drug Discovery Flashcards
Where do small molecules come from?
- Natural Products
- Synthetic Drugs
- Modification of existing drugs
- Screening of existing chemical inventories
- Rational drug design
- Irrational drug design
- Serendipity
What are some natural products
- Penicillin
- morphine
What are some modifications of Existing Drugs
- Promethazine -> Chlorpromazine
- Me too drugs
Screening of existing chemical inventories
- Antibiotics from soil bacteria
- Sulfanilamide from organic dyes
Rational Drug Design
- Mechanism Based- antidepressants
- Structure Based- HIV Protease
- Selective Kinase inhibitors to treat Cancer
Irrational Drug Design
Syn of de novo Chemical Libraries
Seredipty
- Fleming
- Mustard Gas
Structure Activity Relationship (SAR)
Change in structure of molecules leads to large effects in Potency
Quantitative Structure Activity Relationship (QSAR)
- Non-covalent Interactions
- H-bonds
- Dipolar
- Other
Bioisosteric Atom Replacement
- preserves efficacy while improving pharmacokinetics profile
Physical Properties
Solubility, stability
Adverse Effects
- Toxicity
- Drug-Drug interactions
Metabolism
- Prodrug Possibility
- Alterations of Structure for resistance to degradation
Cost to make or obtain
Vancomycin - to complex for large scale
What path do drugs take to become Marketable
10 year process
- Phase 1 - Study, toxicity, dosage
- Phase 2 - Expanded with targeted pt population
- Phase 3 large population trial
- Phase 4 - post market trial
