DrugDesignFunctionalgroupsPharmacologicalActivity.pptVIP

Drug Design: Functional groups / Pharmacological Activity;Structure - Mechanism of action;Structure - Mechanism of action;Active compound identified Target?;Structure - Physiochemical properties Acid / base properties Water solubility Partition coefficient (Crystal structure) Stereochemistry;Cyclopentolate - tertiary amine, pKa ca. 10 ;Antibacterial sulfonamides;Structure - Physiochemical properties Acid / base properties Water solubility Partition coefficient (Crystal structure) Stereochemistry;The more H-bonds possible - the more water sol.;Prediction of water solubility - Empirical;Water solubilization of functional groups;logP ;Absorbtion of Bioactive Compounds;Most drugs: Passive diffusion;Crossing the membrane;Active transport / Carrier mediated transport Less common Structural recemblanse with for instance nutritional compound Transport against conc. gradient Mechanism saturated at high conc. Competition for carrier molecules, compounds with structural resemblance;The Lipinski Rule of Five states that compounds are likely to have good absorption and permeation in biological systems and are more likely to be successful drug candidates if they meet the following criteria: five or fewer hydrogen-bond donors ten (2 x 5) or fewer hydrogen-bond acceptors molecular weight less than or equal to 500 calculated logP less than or equal to 5 *Compound classes that are substrates for biological transporters are exceptions to the rule.;Biomolecules (reseptors, enzymes): Asymmetric;Restricted rotation - optically active rotamers;Screening/Design/Serendipity/Natural products Lead compound Structure Optimisation Actual Drug;Antimycobacterials;Improvement of lead by functional group modification;Bioisosters: Functional groups that results in approx. the same biological properties;Non-classical bioisosters Not strong steric or electronic similarities