Medicinal Chemistry: Drug Design and Discovery
Introduction:
Medicinal chemistry is an interdisciplinary field that combines the principles of chemistry and pharmacology to design, synthesize, and develop new therapeutic agents. The process of drug design and discovery involves a series of steps that require a deep understanding of the biological target, molecular interactions, and physicochemical properties of drug molecules.
Key Concepts:
• Drug targets: A biological target is a specific macromolecule that a drug molecule interacts with to elicit a therapeutic response. The most common drug targets are enzymes, receptors, ion channels, and transporters.
• Drug design strategies: Medicinal chemists use multiple approaches to design drug molecules. These include structure-based drug design, ligand-based drug design, and fragment-based drug design.
• Molecular interactions: Drug molecules interact with biological targets through a variety of non-covalent interactions, such as hydrogen bonding, electrostatic interactions, and hydrophobic interactions.
• Physicochemical properties: The solubility, lipophilicity, and molecular weight of drug molecules are critical properties that affect their pharmacokinetics and pharmacodynamics.
Relevant Equations and Formulas:
• Quantitative structure-activity relationship (QSAR): A mathematical model that correlates the physicochemical properties of drug molecules with their biological activity.
• Lipinski’s rule of five: A set of rules that predicts the oral bioavailability of drug molecules based on their molecular weight, partition coefficient (logP), hydrogen bond donors, and hydrogen bond acceptors.
Examples:
• Design of selective inhibitors for kinase enzymes involved in cancer: Medicinal chemists use structure-based drug design to develop kinase inhibitors that selectively inhibit cancerous cells while sparing normal cells.
• Discovery of new antibiotic compounds: Fragment-based drug design is a powerful approach to discovering novel antibiotics that target bacterial enzymes involved in essential metabolic processes.
• Development of new drugs for central nervous system disorders: Ligand-based drug design is a promising strategy in developing selective ligands for G protein-coupled receptors that are implicated in neurological disorders such as schizophrenia and depression.
References:
- Silverman, R. B. (2015). The organic chemistry of drug design and drug action. Elsevier.
- Morphy, R. (2013). The impact of medicinal chemistry on drug discovery. Nature Reviews Drug Discovery, 12(12), 841-851.
- Hu, Y., & Bajorath, J. (2013). Computational methods for the prediction of drug-target interactions. Current opinion in drug discovery & development, 16(4), 501-508.
