Basic Concepts in Medicinal Chemistry

Index

Introduction
Suggestions for Tutorial Use
Behavioral Objectives
Available and Planned Tutorials
Author Information

Introduction
These tutorials focus on the basic chemical concepts which govern drug action and are meant to serve as a review for the sequence of Biomedical Science & Therapeutics courses (PHBMS 422 - PHBMS 427). These concepts are first introduced in the stand alone Medicinal Chemistry course (PHBMS 421) taught in the Fall semester of the PIV year and should not be foreign to those who have completed this course. It is the expectation of the author that each student understands and masters these concepts since he/she is expected to apply these concepts and understand how they relate to the drugs and drug classes discussed in the BMS&T modules.

Over the years, the author has noticed that some students often do not fully grasp fundamental concepts such as acid/base chemistry, the "dreaded" Henderson-Hasselbach equation, the importance of pH/pKa and ionization, the importance of both water and lipid solubility, key functional groups and their importance to drug binding, stereochemical issues in drug action, and the basic types of drug metabolism. As a result, two situations arise: (1) students must spend too much time relearning these concepts prior to understanding how they apply to new agents and/or (2) students tend to memorize information without totally comprehending the reasons.

For these reasons, a series of tutorials have been planned. This project was begun in June 2001 and updates are posted as the tutorials are developed. Previously available quizzes for functional groups and acid/base identification have been updated and are included here. The author asks your patience as the tutorials are developed. To date, seven tutorials are complete. Topics for the tutorials will be developed in the order listed below. To allow maximum student benefit, tutorials will be available as "works in progress" as they are being completed and will be indicated as such.

Index

Suggestions for Tutorial Use

Students should take the time early in the semester to review those areas which are most problematic for them. In the long run, this will be time well spent.
As new topics are discussed, access the tutorial on an "as needed" basis. If problems arise concerning a particular topic, take the time to review the fundamental concepts first and then "tackle" your notes.
Take the time to answer the review questions. In doing so, thoroughly evaluate all answers and options, since knowingly selecting an incorrect answer may sometimes provided additional information.
NOTE: This tutorial is not meant to completely replace your instructor!! If you still have questions/problems after reviewing the information here, please consult the author (or your instructor).
This tutorial may also help as you prepare for your licensure exam.

Index

Behavioral Objective
The numbers in parentheses following each of the objectives correspond to the seven tutorials listed below and indicate which tutorial(s) address(es) or will address the objective. After reviewing these tutorials, students should be able to:

Identify functional groups present in drug molecules (1)
Identify acidic and basic functional groups. (2)
Classify a drug as either an acid, a base, an amphoteric compound, an electrolyte, or a non-electrolyte. (2)
Solve both qualitative and quantitative pH/pKa problems. (3)
Predict the impact that the acid/base nature of a drug will exert on the solubility of that drug. (3, 4)
Predict the impact that the acid/base nature of a drug will exert on the binding of the drug to its receptor. (3, 5)
Use the acid/base nature of a drug to explain chemical/drug interactions. (3)
Describe the importance of lipid solubility, water solubility, and their importance in oral bioavailability of drugs. (4)
Predict the relative solubility of a drug molecule based on an evaluation of its structure and functional groups. (4)
Evaluate factors which determine oral efficacy and bioavailability. (4)
Explain and predict the influence solubility has on drug metabolism and drug selection. (4)
Predict potential drug-receptor interactions based upon evaluation of the functional groups present within the structure of the drug. (5)
Explain the importance of chelation, acid/base instabilities, and hydrolytic reactions as they relate to drug action, drug interactions, and therapeutic decisions. (5, 6)
Differentiate among the major routes of metabolism and predict metabolic paths based on functional group analysis. (6,7)
Identify common stratagies for developing prodrugs. (7)
Explain the advantages of using prodrugs. (7)
Differentiate among enantiomers, diastereomers, geometric isomers, epimers, and conformational isomers and apply this knowledge to an explanation of drug activity. (8)

Index

Available and Planned Tutorials

All of these tutorials have been converted to DHTML language, meaning that unlike the course specific ones, these do not require the Neuron plug-in. Additionally, they should be MAC accessible via either Internet Explorer or Netscape. Please note: These DHTML versions REQUIRE that your internet browser allows “pop-ups”! Therefore, you may need to change your settings to temporarily allowing pop-ups in order to view these tutorials.

Functional Group Quiz
Identifying Acidic and Basic Functional Groups
Acid/Base Identification Quiz
Solving pH and pKa Problems
Salts and Solubility
Drug Binding Interactions
Metabolism: Phase I Pathways
Metabolism: Phase II Pathways
A Review of Stereochemistry
This tutorial currently contains information regarding chirality and enantiomers. Additional information will be added to this tutorial in the future, specifically, discussions of diastereomers, geometric isomers, conformational isomers, and isosteres.

Index

Author Information

Marc W. Harrold, Ph.D.
Professor of Medicinal Chemistry
Duquesne University
School of Pharmacy
Pittsburgh, PA 15282
harrold@duq.edu
(412) 396-6364