1. MCO1. General introduction to medicinal chemistry.
2. MC02. Ligands & receptors. (1) Ligands. (1.1) Types of ligands. (1.2) Drugs: Definition, classification, drug names. (2) Sites of drug action: biological targets. (3) Proteins as biological targets: (3.1) Enzyme inhibition. Introduction: enzyme characteristics, nomenclature, classification and parts. Mechanism of enzyme action. Enzyme inhibitors (Substrate, product and transition state analogs; competitive and non competitive; reversible and non reversible).(3.2) Interaction of drugs with receptors: Agonists and antagonists. Induced fit theory. Types of protein receptors. Types of membrane receptors (Ion-channel receptors, G protein-coupled receptors, Kinase-linked and related receptors). Intracellular receptors (lipid-soluble hormones).(4) Nucleic acids as biological targets. (5) Lipids as biological targets. (6) Binding forces between ligands and targets. (7) Isomerism.
3. MC03.Target validation. Genomics and Proteomics. Protein expression and purification. Arrays. RNA interference. Knock-outs.
4. MC04. Physico-chemical properties and biological activity. (1) Stages in new drug discovery and development process. Stages in drug action: pharmaceutical, pharmacokinetic and pharmacodinamic phases. (2) Structure of the lipidic membrane. Structure of the most representatives glycerophospholipids. (3) ADMET. Procedures determining the bioavailability of a drug according to its route of administration. (4) Physicochemical models for drug transport through membranes. (5) Absortion: physicochemical properties affecting drug diffusion through membranes. (5.1) Aqueous solubility. (5.2) Degree of ionisation. (5.3) Lipophilicity: partition coefficient. (5.4) Prediction of oral absorption from the physicohemical properties: Lipinski’s rule of five. (6) Drug metabolism. (6.1) Phase I biotransformations: oxidation, dealkylation (N-, O-, S-), reduction, hydrolysis. (6.2) Phase II biotransformations: conjugations (glucuronidation, sulfation, glutathione and amino acids). (6.3) Resulting from the metabolic processes: deactivation, activation, changes in activity, toxic metabolites. (7) Isomerism. (7.1) Pharmacodynamic differences between enantiomers. (7.2) Pharmacokinetic differences between enantiomers.(7.3) No pharmaceutic differences between enantiomers.(7.4) Enantiomers with dual effects. (7.5)Differential toxicity between enantiomers.(7.6) Advantages of using the eutomer. Eutomer vs. racemic.
5. MC05. SAR and basic drug design concepts. (1) Design from known drugs. (2) Pharmacomodulation: homologous series, vinilogues and benzologues, bioisosterism. (3) Pharmacomodulation: conjunctive approach. Duplications and hybrids (metabolically reversible and no reversible). (4) Study of the metabolites: (4.1) Design of bio-reversible drugs: pro-drugs and soft drugs. (4.2) Design of bio-resistant drugs: hard drugs. (5) Study of synthetic intermediates. (6) Study of side effects. (7) Chiral switch. (8) Rational optimization (QSAR).
6. MC06: Hit to Lead Optimization. (1) Properties of a suitable lead substance. (2) Discovery of hits: Active compounds of natural origin; Pharmacomodulation approaches; Semisynthesis. (3)From hit to lead: the problem of target identification. (4) Chemical genetics. Forward genetics”- “Forward chemical genetics. (5) Reverse genetics- Reverse chemical genetics. (6) Small-molecule microarrays. (7) Surface plasmon resonance. (8) Fragment screening. The rule of three, ligand efficiency, fragment screening vs HTS, approaches.
7. MC07. Pharmacokinetics and toxicology. Pharmacokinetics and toxicology. Pharmacokinetic models. Drug absorption and Metabolism Studies. Bioavailavility and mass balance studies. Toxicity. Ecotoxycity.
8. MC08. Drug discovery and development overview. (1) The drug discovery and development process. (2) Drug discovery. (3) Drug development: (3.1) Pre-clinical development. (3.2) Clinical development (General concepts; Models and techniques; Biomarkers, real and surrogate endpoints; Protocols for clinical trials; The phases of clinical testing). (4) Modern technologies of interest for the process of drug development. (5) Time and cost requirements for development of a new chemical entity and factors contributing to project failure. (6) Regulatory problems. (7) How to organize for drug discovery and drug development: (7.1) R&D organizational categories. (7.2) Bussiness model. (7.3) Pharmaceutical R&D philosophy. (7.4) Culture. (8) R&D productivity