Interdisciplinary design of bioactive small molecules: structure–activity relationships, pharmacokinetics, lead discovery and optimisation. Substrate of pharmaceutical R&D.
medicinal-chemistry
Lipinski's rule of five
Empirical heuristic for oral drug-likeness: MW ≤ 500, log P ≤ 5, HBD ≤ 5, HBA ≤ 10. Compounds violating more than one rule have markedly…
Structure–activity relationship (SAR)
Systematic correlation of structural modifications with biological potency. Quantitative SAR (QSAR) regresses log(1/IC50) on molecular…
Lead compound
Chemical starting point with demonstrated biological activity on the target (IC₅₀ typically 100 nM–10 μM) that is iteratively optimised for…
Pharmacokinetics (ADME)
Absorption, Distribution, Metabolism, Excretion — quantified by C_max, T_max, AUC, half-life t_{1/2}, volume of distribution V_d, clearance…
Drug–target interaction
Binding described by K_d = k_off/k_on; residence time t_res = 1/k_off increasingly recognised as better potency predictor than K_d alone.…
Prodrug strategy
Administered pharmacologically-inactive precursor metabolically converted to the active drug in vivo. Used to improve solubility…
Bioisostere
Functional-group substitution preserving key interactions (volume, lipophilicity, H-bonding) while altering metabolism or patent space.…
Fragment-based drug design
Screens small (MW<300) 'fragments' at high concentration via NMR/SPR/X-ray; hits are fused or grown into lead compounds. Delivered e.g.…