Midterm Exam: Wednesday, 220

1
Midterm Exam Wednesday, 2/20

• 10-15 questions
• Short response
• Dont memorize drug structures
• Dont memorize reagents
• Explain reactivity based on structure
• Relationships among concepts
• Application of concepts
• Study sheet on course website
• Look at chapter questions

2
Some questions to consider

• Structure I is an agonist which binds to the
  cholinergic receptor and mimics the action of the
  natural ligand acetylcholine. Structure II, on
  the other hand, shows no activity and does not
  bind to the receptor. Suggest why this might be
  the case.

3

• Isoprenaline undergoes metabolism to give the
  inactive metabolite shown below.
• Suggest why this metabolite is inactive.
• What structural modifications could be made that
  would possibly prevent this metabolism yet retain
  activity?

4

• Fluphenazine is an antipsychotic drug often
  administered as fluphenazine decanoate.
• What is the structure of fluphenazine?
• Fluphenazine decanoate has a prolonged period of
  action when it is given by intramuscular
  injection, but not when it is given by
  intravenous injection. Suggest why this is the
  case.

5

• Morphine binds strongly to opiate receptors in
  the brain to produce analgesia. In vitro studies
  on opiate receptors show that the quaternary salt
  of morphine also binds strongly. However, the
  compound is inactive in vivo when injected
  intravenously. Explain.

6

• Methylphenidate and atomoxetine are used in the
  treatment of attention deficit hyperactivity
  disorder. Suggest possible metabolites for these
  structures.

7

• Acetylcholine is a neurotransmitter that is
  susceptible to chemical and enzymatic hydrolysis.
  Suggest strategies that could be used to
  stabilize the ester group of acetylcholine and
  show the sort of analogues which might have
  better stability.

8

• Oxamniquine is an important Third World drug used
  in the treatment of schistosomiasis (bilharzia).
  Consider the structures below of oxamniquine (A)
  and two of the additional drugs tested in the
  design of oxamniquine. Based on these structures,
  draw the pharmacophore of oxamniquine.

9

• Based on the pharmacophore of oxamniquine you
  determined in the last question, design a
  possible agonist for oxamniquine.

10

• You are a researcher in the area of drug design
  and development. What are some of the factors
  involved choosing a disease as a focus for your
  research?
• How is NMR used in drug design?