Quantitative SAR basics for drug discovery .ppt
- 1. QSAR- simplified M H Ghante Asst prof Dept of Pharmacy GGV, Bilaspur
- 2. What is QSAR • A QSAR relates a numerical description of molecular structure or properties to known biological activity • Activity = f (molecular descriptors) • Success of QSAR: right descriptors + right method (form of f ) • A QSAR should be • explanatory (for structures with activity data) • predictive (for structures without activity data) • A QSAR can be used to explain or optimise: • localised properties of molecules such as binding properties • whole molecule properties such as uptake and distribution
- 3. Physicochemical parameters used in quantitative structure activity relationship (QSAR)- such as •Partition coefficient, •Hammet’s electronic parameter, •Tafts steric parameter and •Hansch analysis.
- 4. Main stereoelectronic properties used in CADD Steric L (Substituent length) B5 ( Substituent width) MR (Molar refractivity) Volume Surface area Electronic σ (Hammet constant) F, R (Field and resonance parameters) pKa (Ionization constants) q (atomic charges) MEP (Molecular Electrostatic Potential)… Lipophilic π (Hansch constant) f (Hydrophic fragmental constant) LogP (partition coefficients) Logkw (capacity factor values from RP-HPLC) CLOGP (calculated log P values) MLP (Molecular lipophilic potential) H-bonding HA (number of H-bond acceptors) HD (number of H-bond donors) ΔlopP (oct-hex) (H-bond capability)…