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Reviews/Testimonials
Basic Concepts of Medicinal Chemistry
By Marc W. Harrold and Robin M. Zavod
Pharmaceutical Journal, Volume 290, Page 343, March 23, 2013
Reviewer: Laurence A Goldberg is a pharmaceutical consultant from Bury, Lancashire
All you need to know about medicinal chemistry.
This book focuses solely on the basic, fundamental concepts governing the discipline of
medicinal chemistry. Every drug is a chemical structure that contains numerous
functional groups arranged in a specific manner. These functional groups determine the
interactions of the drug molecule with its biological target, its pharmacological action,
the route by which it is administered, the extent to which it is metabolized and the
presence or absence of specific adverse reactions or drug interactions.
The chapters in this book have been carefully organized to allow the reader to gain
knowledge progressively about the chemistry of drug molecules, with each chapter
building on the previous one. The first chapter reviews the numbering of alicyclic and
heterocyclic rings, the designation of aromatic ring positions and steroid nomenclature,
while the second chapter focuses on the chemical characteristics of functional groups
and the roles they play in drug action.
The following chapters identify those functional groups that are acidic or basic, review a
strategy to calculate the extent to which they are ionised in a given environment and
then examine how these characteristics contribute to the overall solubility of the drug
molecule. Subsequent chapters discuss the types of binding interactions that can occur
between a drug molecule and its biological target and how stereochemistry of the
molecule can also affect its interaction with biological targets. Emphasis is placed on the
pharmacological and therapeutic differences that can occur between enantiomers.
A chapter is devoted to exploring the metabolism of drug molecules by various
enzymes. It identifies the functional groups that are susceptible to each type of
metabolic transformation, enabling the reader to become more proficient in predicting
the possible metabolic transformations for a given drug molecule. In the final chapter,
the concept of structure-activity relationships is introduced along with the concepts of
molecular modification to design new drugs and analogues of existing drugs. This book
is extremely well structured and easy to follow. It navigates through medicinal chemistry
in a way that makes the subject easy to understand. It will be a great asset to students
embarking upon a healthcare career or to practitioners who need to brush up on
medicinal chemistry.
American Society of Health-System Pharmacists • 7272 Wisconsin Avenue • Bethesda, MD 20814
Reviews/Testimonials
Basic Concepts in Medicinal Chemistry
By Marc W. Harrold and Robin M. Zavod
Pharmacy Teaching and Learning
This text is an excellent addition to the textbooks available to pharmacy students as a
primer before beginning the study of medicinal chemistry. The book is organized into
nine chapter which begins with an Introduction followed by chapters that deal with
Functional Group Characteristics and Roles, Identifying Acidic and Basic-Functional
Groups, Solving pH and pKa Problems, Salts and Solubility, Drug Binding Interactions,
Stereochemistry and Drug Action, Drug Metabolism, and Structure-Activity Relationships
and Basic Concepts in Drug Design. The titles are self explanatory as to their content.
The format for each of the instructional chapters (Chapter 2 – 9) is extremely student
friendly and quite helpful. The chapters begin with a list of learning objectives and
finishes with a summary of key points presented in the chapter along with review
questions. Answers to the review questions appear in the appendix of the book. The
figures within the chapters use actual marketed drugs to demonstrate the concepts
being presented. Uniformity of the structures and highlighted boxes within the
structures makes it easy for students to follow the written presentation. From time to
time the authors use real life analogies to emphasize important concepts. These were
very nicely done and should add to the ability of students to fully comprehend what the
authors are presenting. Another major strength of this book is that when the authors
use drug examples to emphasize a property or properties of drug molecules they
identify the drug, its therapeutic utility, and usually its mechanism of action. These “real
life” examples would be expected to hold the interest of the reader and point out the
relevance and application of the properties and concepts.
I was especially impressed with Chapter 4: Solving pH and pKa Problems, which deals in
part with the topic of the Henderson-Hasselback equation which students usually have
great difficulty with. The authors presented in detail how one can use pH and pKa to
answer questions about degree of dissociation at various pH’s with specific examples
which were easily followed. Chapter 8: Drug Metabolism, was also very well done.
Highlighting key drug metabolisms in a concise manor should greatly help student
master the process of predicting and understanding metabolism and the outcomes of
metabolism.
Overall, I highly recommend Basic Concepts in Medicinal Chemistry as a required text
for pharmacy students, those who are new to medicinal chemistry, as well as those who
might be unaware of how medicinal chemistry contributes to the education of a
practicing pharmacist. In fact, I believe that even “seasoned” medicinal chemists will
find value in reading this book.
Thomas L. Lemke, PhD
Professor Emeritus
University of Houston
College of Pharmacy
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Reviews/Testimonials
Basic Concepts in Medicinal Chemistry
By Marc W. Harrold, BS, Pharm, PhD; Robin M. Zavod, PhD
MedInfoNow: Doody’s Review Services
[REVIEWER'S EXPERT OPINION]
Daniel J. Canney, PhD (Temple University School of Pharmacy)
Description
This book's title is an accurate description of its content. It focuses solely on the most
basic, fundamental concepts governing the discipline of medicinal chemistry and is
written with the pharmacy student in mind. Pharmacy faculty teaching medicinal
chemistry courses should find this useful for the introductory portion of the course.
Students should find the examples, chapter summaries, and review questions/answers
especially helpful in understanding the concepts.
Purpose
An important goal is to present the basic, fundamental concepts governing the discipline
of medicinal chemistry to pharmacy students who often do not appreciate the role of
these concepts in their practice. Getting pharmacy students to understand that
decisions regarding drug therapy are intimately related to the physicochemical
properties of the drugs is an important objective for any medicinal chemistry instructor.
This book should help provide the foundation necessary to better understand later
discussions of specific drug classes.
Audience
The authors clearly state that the intended audience is pharmacy students. The
approach this book uses should be appealing to this group of students.
Features
The book focuses solely on the most basic, fundamental concepts of medicinal
chemistry for an audience of pharmacy students who generally have varying
backgrounds when beginning such a course. It is a good introduction to fundamental
concepts that focus on physicochemical properties of functional groups without
covering specific drug classes. Chapters cover the basics of drug metabolism,
stereochemistry and drug action, and SAR/basic approaches used in drug design. The
coverage of drug classes is better left to well-known medicinal chemistry books, to
which the authors refer readers at the end of the introductory chapter. The illustrations
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are well done, but may be more effective in color. The use of recent examples from the
drug discovery/development literature (drug metabolism, bioisosteres, prodrugs, etc.
with references) might enhance the book.
Assessment
This is an excellent introduction to the fundamental principles of medicinal chemistry,
focusing primarily on the physicochemical properties of functional groups, the broad
concept of structure-activity relationships, the basics of drug metabolism, the
importance of stereochemistry to drug action, and common approaches used in drug
design. The chapter summaries and review questions/answers are effective teaching
tools that should be popular with students. Because this book handles these topics
differently than other books currently in use, it will serve as a supplement to those,
which cover drug classes in more detail. For example, Foye's Principles of Medicinal
Chemistry, 7th edition, Lemke et al. (Lippincott Williams & Wilkins, 2013), handles some
of the same topics, but also goes into specific drug classes in great detail, as does Wilson
and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry, 12th
edition, Beale and Block (Lippincott Williams & Wilkins, 2011). Both of these are among
the books to which the authors refer readers.
Weighted Numerical Score: 80 - 3 Stars
American Society of Health-System Pharmacists • 7272 Wisconsin Avenue • Bethesda, MD 20814
Reviews/Testimonials
Basic Concepts in Medicinal Chemistry
By Marc W. Harrold, BS, Pharm, PhD; Robin M. Zavod, PhD
American Journal of Pharmaceutical Education 2013; 77 (5) Article 107.
Reviewer
Stacy D. Brown, PhD
Bill Gatton College of Pharmacy, East Tennessee State
University, Johnson City, Tennessee
This new medicinal chemistry textbook by Drs. Harrold and Zavod is unlike any other on
the market. The text is succinct and well suited for an introductory or “principles”
course in medicinal chemistry, with 9 chapters. The intention behind this book is the
establishment of a deep understanding of fundamental principles of medicinal
chemistry that could then be applied to specific drug classes, either through a
subsequent course or as part of a curriculum where medicinal chemistry is integrated
with other areas, such as pharmacology and pharmacotherapy. The text possesses
several strong features that help students self-asses their understanding of the
concepts, including review questions at the end of each chapter and clear learning
objectives at each chapter introduction. The review questions that conclude each
chapter are particularly useful because they stick to the concepts of the chapter, and do
not try to branch out into counseling points or therapeutics. This drives home the point
that these questions are for learning medicinal chemistry, and this content will serve as
building blocks for future pharmacy knowledge. The learning objectives that start each
chapter are easily assessable and the summary points throughout the chapters provide
useful recaps of the content, so the “take home” points are not missed.
The book’s Introduction clearly explains the organization of the book and its intention.
While this may not be particularly useful for students, it clarifies for faculty members
how this text can be used. It will especially be helpful for faculty members who have
taught from other texts in the past, but wish to adopt this one because of its unique
approach of focusing heavily on fundamentals.
The second chapter presents functional groups, sticking with the philosophy that each
drug molecule is a sum of several parts (functional groups), and that in understanding
the parts, one can understand the whole. This chapter also offers great coverage of
organic chemistry topics such as resonance, electronegativity, water/lipid solubility,
hydrogen bonding, and steric hindrance in a context that applies them to drug
molecules. An especially strong feature of Chapter 2 is the coverage of the R-groups in
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the amino acids. This is a key topic in understanding drug-target binding, and will help in
equipping those students who have a superficial understanding of amino acid chemistry.
Chapters 3 and 4 are related by their coverage of acid/ base chemistry. Chapter 3 goes
into depth about acidic and basic functional groups, how to recognize them, and how
they contribute to the overall acidic or basic character of a drug molecule. Especially
useful is a tabular summary of acidic and basic functional groups and their respective
pKa ranges. Chapter 4 then builds on this to teach both quantitative and qualitative
approaches for solving Henderson-Hasselbach problems. From an instructor’s
perspective, this chapter offers several approaches to solving these problems; however,
students may find this confusing if they do not carefully read the text that accompanies
each approach.
Chapter 5 transitions the student into applying understanding of functional groups and
pKa to the topic of salts and solubility. There is a thorough coverage of both organic and
inorganic salts, the former of which is not always discussed extensively in other
textbooks. The authors use a presentation of solubility coefficient and partition
coefficient to transition into covering water and lipid solubility, and the therapeutic
implications behind these chemical properties. The focus of Chapter 6 is drug-target
binding, which is a logical next step in applying fundamental principles from previous
chapters. The tendency for drugs to interact with amino acids, or other biomolecules,
within a target site is reliant upon chemical properties such as pKa, solubility, and
partition coefficient, so these concepts are reiterated throughout Chapter 6. The
strength of Chapter 6 lies in the extensive presentation of example drugs from each type
of covalent and non-covalent drug-target interaction.
Chapter 7 presents concepts of stereochemistry, a significant aspect of drug chemistry
that is often not covered in depth in medicinal chemistry textbooks. Students do not
always recall the distinction between different isomer types from their pre-requisite
courses, and this chapter helps to “even the playing field” with regards to prepharmacy
preparation. As stereochemistry is a key aspect to drug binding, this chapter may be
best covered before Chapter 6. Chapter 8 follows with a presentation of drug
metabolism through a thorough overview of all Phase I and Phase II reactions. There are
multiple examples of drugs that are affected by each metabolic reaction, which is better
than a generic molecule that is used in some books for the less common pathways. This
chapter includes an interesting discussion of the chemical basis of the cytochrome P450
names as they relate to the structure of cholesterol. Finally, the discussion of hydrolysis
reactions transitions seamlessly into teaching about pro-drugs and the use of metabolic
activation of drug compounds.
The final chapter, entitled “Structure Activity Relationships and Basic Concepts in Drug
Design,” represents a capstone for the text where students are expected to pull
together concepts from the previous chapters and apply them to looking at drug
structures within a class. The second learning objective of this chapter really
American Society of Health-System Pharmacists • 7272 Wisconsin Avenue • Bethesda, MD 20814
summarizes the intent of the entire book, where the student is expected to compare
drug structures and explain how their differences “could affect their pharmacological,
physicochemical, or therapeutic activity.” This chapter begins with examples of how
structure-activity relationships affect drug binding, ADME (absorption, distribution,
metabolism, and excretion), and pharmacology, and then transitions into specific
structural modifications, including isosteric replacements. This chapter would benefit
from a longer set of review questions at the end, where the integrated nature of the
textbook’s content is emphasized and students are given the opportunity to tie together
the concepts from previous chapters.
In conclusion, this textbook provides a refreshing and unique approach to teaching
introductory medicinal chemistry. There is no impetus whatsoever for the student to be
able to memorize drug structures, but instead the student is taught to critically evaluate
the different parts of the drug molecule and predict how it fits into a class with regards
to pKa, solubility, etc. Instructors who are accustomed to a more traditional approach to
teaching medicinal chemistry may find this text challenging to work with, as they may
disagree with the “depth over breadth” approach presented by this book. However, the
flow of the material in the text is intentional, and the content builds upon itself to end in
a chapter that introduces the concept of structure-activity relationships. Using the endof-chapter review questions as a guide, faculty members could develop ancillary active
learning or on-line modules to accompany the implementation of this textbook in the
medicinal chemistry classroom. If the content is indeed mastered by the student as a
result of using this book, he or she should have the confidence and competence to apply
these fundamental concepts to the study of any drug class moving forward.
American Society of Health-System Pharmacists • 7272 Wisconsin Avenue • Bethesda, MD 20814