Page 8 - Medicinal Chemistry Self Assessment

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PREFACE

If our suspicions are correct, you’ve heard the phrases, “Keep up the good work—you’ll get better with
practice!” and “Keep practicing and you’ll see that it gets easier.” Regardless of whether it is a coach,
teacher, clergy member, scout leader, friend, or family member providing this encouragement, the person
receiving this advice is likely learning a new skill, technique, or language. With practice, soccer goals
are scored, training wheels are removed, piano and ballet recitals are executed, and tents are pitched.
Through self assessment, one is able to both relish the “victory,” as well as consider how he or she could
have improved.

When learning a new language, another common expression is, “If you don’t use it, you’ll lose it.” The
Basic Concepts in Medicinal Chemistry textbook served to lay the “language” foundation for drug struc-
ture evaluation. Whereas written/spoken language is based on phonemic awareness and phonetics, the
language of medicinal chemistry is based on functional group identification and evaluation. These func-
tional groups “speak” to biological targets via key binding interactions, with stimulation or inhibition of
key physiological and biochemical processes as the response. Mastery of this language will help facilitate
a learner’s journey into understanding structure activity relationships—the next level of structure evalua-
tion.

The Basic Concepts in Medicinal Chemistry chapters discussed physicochemical properties, provided clini-
cally relevant examples and, through the review problems, offered an opportunity to practice new struc-
ture evaluation skills. With all of the variations of practice makes perfect ringing in our ears, Marc and I
agreed that one way to help cement the concepts in the textbook chapters is to offer learners a chance
to engage in self assessment. Better yet, we knew that the next step was to put all of the functional
group pieces together to support whole molecule evaluation.
This workbook is split into two sections with two goals in mind. Our first goal is to help the learner
reinforce his or her foundational knowledge. Additional practice problems focus on the following eight
fundamental types of evaluation:

1. Identification of functional groups that contribute to water solubility and those that contribute
to lipid solubility and the need for a balance between the two

2. The role of electron withdrawing and donating functional groups on adjacent atoms and func-
tional groups

3. Identification of acidic and basic functional groups and related ionization under physiologically
relevant conditions

4. Use of the Henderson-Hasselbalch equation to solve both qualitative and quantitative pH and pK
a
problems
5. Formation of inorganic and organic salts of specific functional groups and the value of those salts
6. Interaction chemistry between a drug molecule and its biological target for drug action

7. Spatial orientation of functional groups

8. Metabolic routes of drug activation, inactivation, and/or elimination
Our second goal, and the natural next step in the learning process, is to have the learner put all of his or
her evaluation skills together and fully assess all of the functional groups within a given drug molecule.
Twenty contemporary drugs that span an equivalent number of drug classes were selected as representa-
tive models for whole molecule evaluation. Section questions challenge the learner to anticipate what
could happen to a drug molecule (e.g., what metabolites could form), as well as to provide an explana-
tion for an observed pharmacodynamic (e.g., mechanism of action) or pharmacokinetic parameter (e.g.,
percent orally bioavailability) based on the information gleaned from the structure evaluation process.