Medicinal Chemistry Introduction CH456

Medicinal Chemistry Introduction

• This is an introductory course in medicinal chemistry, CH456.
• The course was created by James H. Gerlach in 2025.

The Five Deadliest Infectious Diseases

• Rabies has an essentially 100% case fatality rate.
• Ebola hemorrhagic fever has an 83% case fatality rate.
• Marburg hemorrhagic fever has an 80% case fatality rate.
• H5N1 avian influenza has a ~60% case fatality rate.
• Nipah virus has a 40% to 70% case fatality rate.

Share of Total Disease Burden by Cause, World 2021

• This data measures the total burden of disease, including years of life lost and years lived with disability.
• One DALY (Disability-Adjusted Life Year) equals one lost year of healthy life.
• Cardiovascular diseases and respiratory infections and tuberculosis are among the leading causes.
• The data is categorized by cause (e.g., cancers, respiratory infections, etc.)

Share of Total Disease Burden by Cause, Canada 2021

• Similar to the global data, this data measures the disease burden in Canada.
• Leading causes include cancers, cardiovascular diseases, and musculoskeletal diseases.
• The data is divided into communicable, maternal, neonatal, nutritional diseases, and injuries.

Disease Burden From Communicable, Maternal, Neonatal and Nutritional Diseases, World

• This chart displays the estimated disease burden from communicable, maternal, neonatal, and nutritional diseases.
• Burden is measured in DALYs (Disability-Adjusted Life Years) per year.
• It shows a downward trend in disease burden over time for these disease categories around the world.

Disease Burden From Communicable, Maternal, Neonatal and Nutritional Diseases, Canada

• Similar to the global data, this chart displays the estimated disease burden from communicable, maternal, neonatal, and nutritional diseases in Canada.
• The data reveals a fluctuating pattern over time in Canada.

Deaths from Infectious Diseases, 1980 to 2021

• The chart tracks the estimated number of deaths annually due to various infectious diseases worldwide.
• There is a clear declining death rate pattern for the world.
• The chart also displays a similar downward trend.

Global Trends in the Estimated Number of TB deaths and Mortality Rate for 2000-2020

• This chart illustrates the global trend in TB deaths over a 20-year period (2000-2020).
• It shows the estimated number of TB deaths per year (log scale) and the mortality rate per 100,000 population per year (log scale).

The Deadliest and Most Communicable Diseases

• This chart categorizes diseases by fatality and communicability.
• It visualizes diseases like Rabies, Ebola, and various types of influenza.

Malaria is the Disease Responsible Historically for the Most Worldwide Deaths

• Malaria is deadly and preventable.
• It is transmitted by infected female Anopheles mosquitoes and it is a major worldwide concern.
• In 2023, there were an estimated 263 million cases and 597,000 deaths. Cases and deaths have been reported in Africa.

Countries with Indigenous Cases of Malaria in 2000 and Their Status by 2023

• A world map displays the status of malaria cases. 

True Size of Africa

• Africa's size in relation to other countries is displayed for understanding.

Quinine

• Cinchona bark, from South American trees, contains quinine.
• Quinine treats malaria, and quinidine treats heart conditions.
• The Countess of Chinchón was the first European reportedly cured from malaria using Peruvian bark.

Homeopathy and Cinchona

• Dr. Samuel Hahnemann, the founder of homeopathy, studied cinchona bark effects.
• Hahnemann's alleged hypersensitivity to cinchona bark is a historical aspect of homeopathy.

Discovery of the Malaria Parasite

• Alphonse Laveran, a French military doctor, discovered a motile parasite causing malaria after a posting to Algeria in 1878.
• He was awarded the Nobel Prize in 1907.

Quinine

• Quinine is a white crystalline alkaloid.
• It's antimalarial, analgesic, antipyretic, anti-inflammatory, and has a bitter taste.

Quinine Total Synthesis Milestones

• Efforts spanning over 150 years led to quinine total synthesis.
• Major figures include Pelletier, Caventou, Pasteur, Perkin, Rabe, Kindler, Woodward, Doering, Stork, Kondo, and Mori among others.
• There were various difficulties, and debates regarding validity of the synthesis methods and results.

Woodward-Doering Quinine Synthesis

• The Woodward-Doering method for quinine synthesis is a historical and crucial milestone in organic chemistry.
• The pathway and details of the synthesis are illustrated in the image.

Quinine Total Synthesis

• Rabe and Kindler synthesized quinine from quinidine in 1918.
• Their method was a crucial step toward quinine total synthesis.
• There were debates and challenges about the validity of early syntheses.

Related Antimalarial Drugs

• Chloroquine (1934) and Amodiaquine (1948) are related antimalarial drugs.
• Their chemical structures are shown in the slides.

Paracetamol (Acetaminophen)

• Paracetamol (Acetaminophen) is a widely used analgesic.
• Its chemical structure and IUPAC name are mentioned.

Paracetamol Total Synthesis.

• There are steps involved in the generation of Paracetamol.
• Fractional distillation is one of the key steps in generating the paracetamol.

Paracetamol Mechanism of Action

• Paracetamol acts through cyclooxygenase (COX) enzyme pathways.
• It also acts by metabolizing in the body to AM404 which inhibits uptake of anandamide.

Paracetamol Metabolism

• Paracetamol is mainly metabolized in the liver to sulfate and glucuronide conjugates.
• Toxic metabolites also form due to CYP metabolic pathways.
• Glutathione helps detoxify these toxic metabolites.

Reactions Involved in Paracetamol Metabolism

• The various reactions involved in metabolizing Paracetamol are shown.
• The pathway also shows the toxic metabolic reaction.

NAPQI Toxicity

• NAPQI (N-acetyl-p-benzoquinone imine) is a toxic metabolite of paracetamol.
• It causes covalent binding to cellular proteins, causing DNA damage.

Treating Paracetamol Overdoses

• Treatment for paracetamol overdose involves acetylcysteine to replenish glutathione levels.
• Early intervention is crucial for success in paracetamol overdose cases.

This quiz introduces the foundational concepts of medicinal chemistry as outlined in course CH456 by James H. Gerlach, created in 2025. Explore key principles and significant aspects of the field that influences drug development and therapeutic applications.