Università Roma Tre

5.000 / 5.000
1. Introduction to Medicinal Chemistry
Definitions: Drug and medicinal product. History. Fields of medicinal chemistry and the role of the medicinal chemist in the modern drug discovery and development process. Origin of drugs: natural drugs, semi-synthetic drugs, synthetic drugs, biotechnological drugs (outline), cell therapies (outline).
2. Essential notions of organic chemistry and biochemistry preparatory to medicinal chemistry
Organic chemistry and biochemistry for medicinal chemistry: recognition of functional groups, amino acids, nitrogenous bases, sugars, mixed structures from 2D and 3D structures, representation of organic molecules in 1D, 2D, and 3D. Proteomics and Genomics in Drug Discovery. Structure of Protein and Nucleic Macromolecules (tertiary structure of DNA and structure and functions of RNA).
3. Pharmaceutical Phase and Pharmacokinetics
Definitions. Pharmacokinetics: Routes of Drug Administration (Enteral, Rectal, Parenteral, Topical), Drug Absorption (Chemical Factors, Biological Factors). Absorption by Passive Diffusion and Oral Route (Lipinski's Rule). Drug Distribution. Bioavailability. Plasma Protein Binding. Drug Metabolism: First-Pass Metabolism, Phase I Metabolism (Structure and Reactions of Cytochrome P450, Oxidative Cycle, Oxidative Reactions Catalyzed by Other Enzymes, Reduction Reactions, Hydrolysis Reactions, Metabolic Activation), Phase II Metabolism (Conjugation Reactions, Conjugation Cofactors, Glucuronidation, Sulfoconjugation, Glutathione Conjugation, Methylation and Acetylation, Dopamine Metabolism, Hippurate Conjugation). Example of Phase I and II Metabolism: Aspirin, Metabolic Stability, Hard and Soft Drugs, Metabolism of the Antiviral Agent Indinavir. Drug Elimination.
4. Pharmacodynamic Phase
Drug/Macromolecule Interactions, Types of Interactions, Covalent Bonds, Ionic Bonds, Ion-Dipole and Dipole-Dipole Interactions, Hydrogen Bonds, Charge-Transfer Complexes, Hydrophobic Interactions, Cation-Pi Interactions, Halogen Bonding, Van der Waals or London Forces, Nonbonding Interactions, Numerical Determination of Interactions. Enzymes as Drug Targets (Types of Inhibitors, Enzyme Kinetics). Receptors (classification, orphan receptors, design of agonist ligands, antagonists, partial agonists, and inverse agonists, desensitization and sensitization, tolerance and dependence, receptor types and subtypes, affinity, efficacy, and potency). Nucleic acids as drug targets. Other drug targets.
3. Drug Discovery and Development
Identification of prototype (hit), hit-to-lead, and lead compounds. Optimization of target interactions. Structure-activity relationships (SAR). Identification of a pharmacophore. Strategies adopted in drug design (substituent variation, structure extension, linear and cyclic homology, variation of the nature of cycles, cycle fusion, isosteres and bioisosteres, structural simplifications, structure rigidification, drug design based on the structure of the interaction site and molecular modeling, multitarget drugs).
4. Antibacterials/Antibiotics
The bacterial cell. Classification by mechanism of action. Metabolite synthesis inhibitors. Folate synthesis inhibitors. Sulfonamides: Origin, mechanism of action, structure-activity relationships, pharmacokinetics, applications. Prontosil, metabolism of prontosil. Trimethoprim: structure, mechanism of action, and association with sulfonamides. Inhibitors of bacterial cell wall biosynthesis. Penicillins: origin, mechanism of action, resistance, methods of preparation of penicillins: 6-APA. [S], structure-activity relationships, structural analogues of penicillin. Benzylpenicillin (G). Phenoxymethylpenicillin (V). Acid sensitivity. Acid-fast penicillins. Beta-Lactamase-Resistant Penicillins (Methicillin, Nafcillin, Temocillin, Oxacillin, Cloxacillin, Flucloxacillin, Dicloxacillin). Broad-Spectrum Penicillins (Penicillin N, Penicillin T, Ampicillin, Amoxicillin, Pivampicillin, Talampipicillin, Bacampicillin). Penicillin Prodrugs. Carboxypenicillins (Carbenicillin, Carfecillin, Indanylcarbenicillin, Ticarcillin). Ureidopenicillins (Azlocillin, Mezlocillin, Piperacillin). Clinical Aspects. Cephalosporins: History and Overview. Properties of Cephalosporin C and SAR. Methods for the Preparation of 7-ACA [S] for the Synthesis of Cephalosporins. First Generation Cephalosporins (Cephalothin, Cephaloridine, Cefalexin [Synthesis of 3-Methylated Cephalosporins], Cefazolin), Second Generation Cephamycin C, Cefoxitime and Oximinocephalosporins [Cefuroxime], Ceftazidime), Third Generation Cephalosporins (Cefotaxime, Ceftizoxime, Ceftriazone), Fourth Generation Cephalosporins (Cefepime, Cefpirome), Fifth Generation Cephalosporins (Cefamicin C, Cefoxitime and Oximinocephalosporins [Cefuroxime], Ceftazidime),

Medicinal Chemistry (G. Costantino, G. Sbardella)
Medicinal Chemistry (G.L. Patrick)
Foye's Principles of Medicinal Chemistry
Medicinal Chemistry (A. Gasco, F. Gualtieri, C. Melchiorre)