1. THE ROLE OF MOLECULAR
PROPERTY PREDICTORS
IN DRUG DISCOVERY
Anu Sharma
Sales Manager – San Francisco, CA

2. The jargon we hear and the jargon speak !!!
What must we know and why?
Lipinski’s Rule
Hydrogen-Bond donor acceptor
Virtual molecules
Compound Libraries
Screening Molecular Modeling
Structure Tables
Proteins
Biological data
R-Group decomposition
Log P Sub-structure searching
Main Scaffold
Key reactants Fragmentation
IC50 EC50
Oral Bioavailability
Drug-Like properties
Combinatorial libraries Custom synthesis
Medicinal Chemistry department
Library Design
Metabolic pathway CADD
Batch Mode Calculations
Active compounds Metabolites
Analoging Pharmacophore
Binding
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
Canonicalization
Reterosynthetic analysis
Millions of compounds
And many more…….

3. From bench side to bed side, what does it take?

4. When the prospects talk, where do they come from?

5. 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 –
i) Hydrophobic
ii) Hydrophilic
iii) Ionic
iv) Steric
E. Lead Identification Stage –
High Thruput Screening “Hit to Lead”
F. Lead Optimization Stage –
Structure Activity Relationships “SAR”

6. 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
Ionization  pKa
Blood brain barrier penetration  LogP/LogD
Computer Aided Drug Designing – CADD
Virtual screening (FBDD, SBDD, MCS, Physicochemical properties )
Space & Freedom - Intellectual Property
Patents

7. References
• 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

8. THANK YOU
FOR YOUR TIME & ATTENTION
Anu Sharma