MedChem exam content

 

á            Explain terms pharmacodynamics, pharmacokinetics, bioavailability

á            Uptake routes for drugs

á            Body fluid compartments, volume of distribution

á            Drug absorption in the intestinal tract, transport through epithelial cells

á            Blood-brain barrier

á            Efflux pumps

á            Binding to plasma proteins

á            Metabolic phase 1 and 2

á            Elimination of drugs

á            Dosing

á            Drug toxicity

á            Phases of drug development

á            Target identification

á            Biophysics of drug-receptor interactions

á            Polar surface area

á            Binding affinities

á            Properties of fragments,leads and drugs

á            Lipinski rules

á            Screening techniques

á            Virtual screening

á            Isosters/bioisosters

á            QSAR relationsships

á            Hansch equation (which terms are included?)

á            3D QSAR

á            pharmacophores

á            changing solubility

á            prodrugs

á            drug delivery systems

á            fragments-based drug design, SAR-by-NMR

á            properties of fragments vs drugs

á            rational drug design

á            methods (roughly): X-ray,NMR,SPR, Ultracentrifugation, ITC, DSC, Thermafluor

á            most important receptors, mode of action, structures (roughly)

á            dose-response curves, binding curves, definition of Kd, agonist, antagonist (full and partial, inverse ag.)

á            determination of Kd

á            antibacterials: strategies, membranes of mammalian, gram +/- cells, action and targets of antibiotics

á            antiviral drugs:strategies, HIV/influenza treatments

á            anticancer drugs: hallmarks of cancer, mode of action of anti-cancer drugs, antibodies

á            anti-inflammatory drugs: immune response, innate and adaptive immune system, pain mediators

MedChem exam content (part D. Obrecht)

1.      Introduction: The Drug Discovery and Development Process

á        Drug absorption, distribution and elimination

á        Bioavailability

á        AUC

2.      Lead Discovery and Lead Optimization-Drugability

á        Drugability: LipinskiÕs rule of 5

á        Drugability parameters

á        Shape analysis

á        Is there a difference between leads and drugs? the rule of 4

á        Fragments: the rule of 3

á        Privileged structural elements

á        Bioisosteres

á        Unwanted molecular properties

3.      Combinatorial and Parallel Synthesis in Medicinal Chemistry

á        Historical background-objective

á        The role of combinatorial chemistry and parallel synthesis in drug discovery

á        Compound mixtures versus single compounds

á        Solid phase synthesis versus synthesis in solution

á        Parallel versus split-mixed synthesis

4.      Combinatorial synthesis of Biopolymers

á        Linear, modular synthesis of biopolymers

á        Solid-phase synthesis of polypeptides; peptoids; oligosaccharides

á        Parallel synthesis vs combinatorial synthesis: split-mixed synthesis

á        Examples for solid-phase synthesis: Split-mixed synthesis; tagging strategies; pin synthesis; tea-bags; photolithography; radiofrequency tags; binary encoding; factor Xa inhibitors; thrombin inhibitors; inhibitors of protein-protein interactions; hot spots and o-rings; synthesis of a-helix mimetics; phage libraries;

á        Peptide mimetics

5.      Strategies for the Synthesis of Small Molecule Libraries

á        Library synthesis planning

á        Synthesis strategies

á        Classical multi-component reactions (MCRÕs)

á        Sequential multi-component reactions (SMCRÕs)

á        Diversity-oriented synthesis (DOS)

á        Collective synthesis of natural products

á        Fragment-based lead discovery

á        Dynamic Combinatorial Synthesis;

á        Target-guided synthesis (TGS)

á        Disulfide thethering; click chemistry

á        Most important reactions used in parallel and combinatorial synthesis

á        Most important building blocks used in parallel and combinatorial synthesis

á        Parallel and/or combinatorial synthesis

á           Parallel work-up