MedChem exam content

 

            Explain terms pharmacodynamics, pharmacokinetics, bioavailability

            Uptake routes for drugs

            Body fluid compartments, volume of distribution

            Drug absorption in the intestinal tract, transport through epithelial cells

            Blood-brain barrier

            Efflux pumps

            Binding to plasma proteins

            Metabolic phase 1 and 2

            Elimination of drugs

            Dosing

            Drug toxicity

            Phases of drug development

            Target identification

            Biophysics of drug-receptor interactions

            Polar surface area

            Binding affinities

            Properties of fragments,leads and drugs

            Lipinski rules

            Screening techniques

            Virtual screening

            Isosters/bioisosters

            QSAR relationsships

            Hansch equation (which terms are included?)

            3D QSAR

            pharmacophores

            changing solubility

            prodrugs

            drug delivery systems

            fragments-based drug design, SAR-by-NMR

            properties of fragments vs drugs

            rational drug design

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

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

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

            determination of Kd

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

            antiviral drugs:strategies, HIV/influenza treatments

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

            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

        Drug absorption, distribution and elimination

       Bioavailability

       AUC

2.      Lead Discovery and Lead Optimization-Drugability

        Drugability: Lipinskis rule of 5

        Drugability parameters

        Shape analysis

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

        Fragments: the rule of 3

        Privileged structural elements

       Bioisosteres

        Unwanted molecular properties

3.      Combinatorial and Parallel Synthesis in Medicinal Chemistry

        Historical background-objective

        The role of combinatorial chemistry and parallel synthesis in drug discovery

        Compound mixtures versus single compounds

        Solid phase synthesis versus synthesis in solution

        Parallel versus split-mixed synthesis

4.      Combinatorial synthesis of Biopolymers

        Linear, modular synthesis of biopolymers

        Solid-phase synthesis of polypeptides; peptoids; oligosaccharides

        Parallel synthesis vs combinatorial synthesis: split-mixed synthesis

        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;

        Peptide mimetics

5.      Strategies for the Synthesis of Small Molecule Libraries

        Library synthesis planning

        Synthesis strategies

        Classical multi-component reactions (MCRs)

        Sequential multi-component reactions (SMCRs)

        Diversity-oriented synthesis (DOS)

        Collective synthesis of natural products

        Fragment-based lead discovery

        Dynamic Combinatorial Synthesis;

        Target-guided synthesis (TGS)

        Disulfide thethering; click chemistry

        Most important reactions used in parallel and combinatorial synthesis

        Most important building blocks used in parallel and combinatorial synthesis

        Parallel and/or combinatorial synthesis

           Parallel work-up