THE ROLE OF MOLECULAR
IN DRUG DISCOVERY
Sales Manager – San Francisco, CA
The jargon we hear and the jargon speak !!!
What must we know and why?
Hydrogen-Bond donor acceptor
Screening Molecular Modeling
Log P Sub-structure searching
Key reactants Fragmentation
Combinatorial libraries Custom synthesis
Medicinal Chemistry department
Metabolic pathway CADD
Batch Mode Calculations
Active compounds Metabolites
Ligands Small Molecules
Molecular properties Organic Synthesis
SAR – QSAR tables
Structure Activity Relationships
Synthetically feasible molecules
Reaction schemes LogD
Polar Surface Area Patents
Lead optimization Clustering of data
Millions of compounds
And many more…….
From bench side to bed side, what does it take?
When the prospects talk, where do they come from?
Discovering Drugs – How does the magic happen?
A. Types of Drugs –
1) Small Molecules
2) Proteins & antibodies
B. Site of action – Receptor
C. Mechanism –
Drug + Receptor = [Complex] = Effect
D. Interactions –
E. Lead Identification Stage –
High Thruput Screening “Hit to Lead”
F. Lead Optimization Stage –
Structure Activity Relationships “SAR”
Drive the SAR forward !!! Who will do that?
Active Compounds - Molecular Properties – “Drug-Like” promise
Key parameters used –
Physical Properties – Rule of 5 Lipinski’s cal
Potency - Lipophilicity LogP
Selectivity - Binding affinity – Measure of charge LogD/HBDA
Solubility – Permeability – Oral Bioavailability TPSA
Blood brain barrier penetration LogP/LogD
Computer Aided Drug Designing – CADD
Virtual screening (FBDD, SBDD, MCS, Physicochemical properties )
Space & Freedom - Intellectual Property
• For more details on this subject –
• "Organic Chemistry Of Drug Design & Drug Action" - by
Richard B Silverman.
• "Medicinal Chemistry : Principles & Practice" - by King.
• Tutorial on Drug Discovery & Development – Jen Eckstein
Posted on the forum – Sales Meeting 2010