ACSI Medicinal Chemistry Notes 2022 - 2023

Year 5 - 6 (20 2 2 - 2023 ) IBDP Chemistry HL Option D Medicinal Chemistry D1 – Pharmaceutical Products and Drug Action Pg 1 Essential idea: Medicines and drugs have a variety of different effects on the functioning of the body. D2 – Aspirin and Penicillin Pg 14 Essential idea: Natural products with useful medicinal properties can be chemically altered to produce more potent or safer medicines. D3 – Opiates Pg 22 Essential idea : Potent medical drugs prepared by chemical modification of natural products can be addictive and become substances of abuse. D4 - pH regulation of the stomach Pg 27 Essential idea: Excess stomach acid is a common problem that can be alleviated by compounds that increase the stomach pH by neutralizing or reducing its secretion. D5 - Antiviral medications Pg 42 Essential idea : Antiviral medications have recently been developed for some viral infections while others are still being researched. D6 - Environmental impact of some medications Pg 52 Essential idea: The synthesis, isolation, and administration of medications can have an effect on the environment. D7 – Taxol – a chiral auxiliary case study Pg 64 Essential idea: Chiral auxiliaries allow the production of individual enantiomers of chiral molecules. D8 – Nuclear Medicine Pg 70 Essential idea: Nuclear radiation whilst dangerous owing to its ability to damage cells and cause mutations can also be used to both diagnose and cure diseases. D9 – Drug detection and Analysis Pg 92 Essential idea: A variety of analytical techniques is used for detection, identification, isolation and analysis of medicines and drugs.

D1. Pharmaceutical products and drug action Understandings : In animal studies, the therapeutic index is the lethal dose of a drug for 50% of the population ( LD 50 ) divided by the minimum effective dose for 50% of the population ( ED 50 ). In humans, the therapeutic index is the toxic dose of a drug for 50% of the population ( TD 50 ) divided by the minimum effective dose for 50% of the population ( ED 50 ) . The therapeutic window is the range of dosages between the minimum amounts of the drug th at produce the desired effect and a medicall y unacceptable adverse effect. Dosage, tolerance, addiction and side effects are considerations of drug administration. Bioavailability is the fraction of the administered dosage that reaches the target part of the human body. The main steps in the development of synthetic drugs include identifying the need and structure, sy nthesis, yield and extraction. Drug – receptor interactions are based on the structure of th e drug and the site of activity. Applications and Skills : Discussion of experimental foundations for therapeutic index and therapeutic window through both animal and human studies. Discussion of drug administration methods. Comparison of how functional groups, polarity and medicinal ad ministration can affect bioavailability. Guidance: For ethical and economic reasons, animal and human tests of drugs (for LD50/ED50 and TD50/ED50) respectively should be kept to a minimum. Page 1

Drugs The effects of drugs and medicines A drug is a natural, synthetic or semi - synthetic substance that results in one or more of the following changes within the body: Alters incoming sensory sensations (from eyes, ears and other sense organs) . Alters mood or emotions. Alters the physiologic al state, i ncluding consciousness , metabolic activity level or coordination. Medicinal drugs (medicines or pharmaceuticals ) are taken to improve the physical and mental health. They have a therapeutic action that benefits the body. OTC refers to Over - The - Counter, d rugs that can be bought at a pharmacy and not requiring a prescription from a medical doctor. Examples include mild analgesics (pain killers) and antacids. Administration of drugs The majority of drugs need to be absorbed into the blood stream to reach their target cells. The method of drug administration determines the biological route taken by the drug and the rate at which it enters the plasma of the blood. The five main methods of drug deliver y are: oral (by mouth), inhalation (into the lungs) , rectal (through the blood vessels of the anus) and by injection (parenteral) using a hypodermic needle , a faster absorption method for th e drug to enter the bloodstream . Some drugs in the form of creams can also be applied topically onto the skin (transdermal). Figure 1.1 Page 2

Summary of common methods of drug delivery by injection Development and testing of new medicinal drugs The research and development of new drugs is a long and expensive process. A new lead compound (with biological activity) may be isolated and purified from an existing species, often a plant, fungus or marine organism. However, medicinal drug development o ften starts by finding an active compound from ‘chemical libraries’ containing thousands of synthetic drugs. A lead compound is often chemically modified to improve its physical properties and biological effect s . Some new medicinal drugs are developed b y a process of rational design. They are designed and synthesized knowing the structure and shape of the receptor the drug molecule interacts with. A potential drug candidate need s to undergo extensive testing in vitro testing with bacteria, cells or bio logical molecules and later with animals . A nti - cancer drugs, are tested with cancer cells grown in culture. The results of large scale animal testing will establish the lethal dose required to kill 50% of the animal test population. This is know n as the LD 50 value , but it is also important to carry out tests that identify chronic, long term toxicity, which is non - lethal. A large LD 50 value means that the substance is relatively non - toxic and that a large quantity of the substance is required to cause a toxic response. A small LD 50 value means that the substance is relatively toxic and that only a small quantity of the substance is needed to cause a toxic response. The effective dose required to bring about a measureable effect in 50% of the test animal population will also be determined. This is known as the ED 50 value. The therapeutic index for animals = 𝐿𝐷 50 𝐸𝐷 50 . Figure 1.2 Inhalation LD 50 values of common fuels Page 3

Drugs will then be subjected to a variety of clinical testing phases with volunteers (first phase) and at later stages with human patients subject to approval by a drug regulatory authority , for example, FDA (Food and Drug Admin i stration) in US . In humans the therapeutic index = T D 50 E D 50 , where TD 50 represent the toxic dose for 50% of the human test population. Figure 1.3 Summary of the steps in the development of a new drug Human cli