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Prodrugs - Philadelphia University Initial definition: A pharmacologically inactive chemical entity that when metabolized or chemically transformed by a mammalian system is converted into a pharmacologically active substance “Drug Latentiation” – included later
PowerPoint Presentation - Modern Synthetic Approaches to Drug . . . What About Drug Discovery in Academia? Forward Chemical Genetics = screening small molecules for their ability to perturb cellular pathways, followed by identifying the specific targets of the active compounds In general, whole cell assays are used
Drug Discovery and Development - SMU Basic Steps Choose a disease Choose a drug target Identify a “bioassay” bioassay = A test used to determine biological activity Find a “lead compound” “lead compound” = structure that has some activity against the chosen target, but not yet good enough to be the drug itself
PowerPoint Presentation Both methods are defined as the analytical methods that can be used for the determination of the content of the active compounds in pharmaceutical preparations and in pure forms
Medicinal Chemistry - lossiehigh. co. uk Computational chemistry Computer-generated models of possible active compounds can then be matched with the enzyme or active site From this, a list of target molecules can be drawn up and chemists can devise methods to synthesise these molecules in the laboratory so that they can be tested for pharmacological activity
Chemical Reactions To predict if a single replacement will react, use the ACTIVITY SERIES The free element MUST BE more reactive than the element in the compound If the free element is MORE ACTIVE than the element in the compound, the reaction WILL OCCUR
INTRODUCTION to Pharmacology Metabolism occurs mainly in the liver (CYP450 system) Metabolism may result in formation of active metabolites (diazepam – nordiazepam) Prodrugs lack activity until they undergo bioactivation (clorazepate – nordiazepam) Metabolism involves two phases: Phase -1 reaction: (catabolic) it includes: oxidation, reduction, and hydrolysis reaction