Drug Nomenclature and Discovery

Drug Nomenclature

• Generic names don't have capitalized letters and are used to discuss the functionality of a drug.
• Brand names have their first letters capitalized and don't reveal much about the drug.
• Three main names for drugs: Chemical name (IUPAC), generic name, and trade name.
• Chemical names are complex and mainly used for regulations.

Drug Discovery

• Generic names are used for advertising drugs.
• Brand names depend on the company selling the drugs.
• Biologics involve extracting natural biological sources for drug repurposing.
• Biopharmaceuticals use modern biotechnological and computational techniques for modifying existing pharmaceuticals.
• Early drug development is based on the observation of natural products.
• Medicinal chemistry focuses on optimizing existing chemical products, such as enhancing a molecule's affinity to its target.

Drug Design and Optimization

• Bioassays are used to screen the activity of various chemicals against a predetermined target.
• Drug design can be done on targets obtained from tissues or genes extracted from patients.
• Molecular docking is a computational technique that predicts how drugs bind to specific sites on target proteins.
• Optimization of drugs aims to increase selectivity and effectiveness.
• Structure-Activity Relationship (SAR) studies how a drug's functional groups interact with target receptors.
• Quantitative Structure-Activity Relationship (QSAR) quantifies the physical properties of a drug and their impact on its biological activity.

Drug Discovery Techniques

• Drug discovery is a challenging process, with a success rate estimated at 50%.
• Nuclear Magnetic Resonance (NMR) bioassays compare regular protein signals with signals after the addition of a potential drug candidate.
• Surface Plasmon Resonance (SPR) measures binding events by detecting changes in light reflection at a metal surface.
• Isothermal Titration Calorimetry (ITC) measures the heat changes that occur when molecules bind, providing information about binding affinity.
• Stereospecific reactions occur when the product of a chemical reaction depends on the specific conformation of the reactant.
• Stereoselectivity describes a compound's preference for reacting with certain candidates.
• Target specificity and selectivity ensure a drug only targets a specific receptor or enzyme in a specific area of the body.

Agonists and Antagonists

• Agonists are drugs that mimic the action of natural compounds.
• Antagonists block the action of natural compounds.
• A pitfall of agonists is that changing the molecule's conformation can change its binding outcome.
• Amide-analogue alkenes are similar to regular alkenes and cannot be rotated.

Drug Metabolism and Modifications

• Deprotonation of carboxylic acid prevents it from being a hydrogen bond donor.
• Ester hydrolysis in vivo can be different from in vitro.
• Alkyl halides have a strong affinity for nucleophilic groups.
• Aryl halides typically don't react directly with alkyl amines under standard conditions.
• Azathioprine prolongs its interaction with glutathione by creating an electron-deficit area.
• Valium prolongs its activity by having a hydrophobic methyl group instead of a hydrogen atom.
• Aspirin masks salicylic acid's toxic phenolic group by turning it into an ester.
• Carbidopa acts as a sentry drug, inhibiting the conversion of levodopa to dopamine outside the brain, but not in the brain.
• Dopamine cannot be administered directly because it is quickly deactivated and metabolized in the body.

Computational Medicinal Chemistry

• Molecular mechanics uses computational analysis to study drugs.
• High-throughput screening has favoured computational analysis over bioassays.
• Computational Drug Design (CADD) models the structure, energy, and binding of ligands and receptors.
• Native conformation refers to the conformation of a molecule in its natural environment, typically aqueous.
• Native conformations are considered stable.

Studying Drug Molecules

• Space-filling representation model shows the space occupied by each atom in a molecule.
• The computer models two key aspects: ligand and receptors.
• Energy calculation is done through modelling.