MEDICINAL CHEMISTRY II

EXAM #2
March 23, 2007

Name Med. Chem Number

SECTION A. Answer each question in this section by writing the letter corresponding to the
best answer on the line provided (2 points each; 50 points total)

1. The drug illustrated below:

CO2 H I Irreversibly inhibits cyclooxygenase
II Undergoes metabolic hydrolysis to salicyclic acid
O III Is an organic acid that can irritate the stomach
O CH3
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

2. The drug illustrated below is:

I Can readily enter the CNS because it is non-polar
O II Is used primarily as an analgesic during childbirth
H C OH III Is administered with atropine for control of diarrhea
N C C CH2 CH2 N
Cl

a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
3. The drug illustrated below:
H CH 3 I Has good antitussive activity
N H 2 PO4 II Can undergo metabolic conversion into morphine
H III Has no affinity for μ-receptors because of the 7,8-
double bond

H 3CO O OH
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
1
 2
4. The drug illustrated below:
I Is susceptible to environmental oxidation at the
O H CH 2CH3 amino group and should be stored under nitrogen
H2N COCH 2CH 2 N II Is metabolized rapidly by ester hydrolysis
CH 2CH3 III Is usually administered together with atropine to
Cl
reduce its abuse potential
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

5. The drug illustrated below:

CO2 H I Is likely to cause methemoglobinemia in susceptible
CH 3
H patients
N CH3 II Is a salicylate NSAID
III Is used to treat mild to moderate pain
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

6. The drug illustrated below:

CH 3 I Is a cis-1,2-disubstituted cyclohexane derivative
H
N II Contains the necessary pharmacophore for a μ-agonist
H 2C CH 3
and is used to treat pain
H Cl III Is a trans-1,2-disubstituted cyclohexane derivative

HO
H 3CO
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

7. The drug illustrated below:

I Is a salt of citric acid
S H CH 2OCH 3 II Is an extremely potent analgesic
CH2CH 2 N III Can be used to induce and maintain
N C CH2CH 3 anesthesia during surgery
O CH 2CO2
HO CO2H
CH 2CO2 H
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
 3
8. The drug illustrated below:
N I Can be used at high doses as an antidote to cyanide
poisoning
H3C CH 3
N S N II Is used at high doses for treating
CH3 Cl CH3 methemoglobinemia
III Is used to treat an overdose of acetaminophen
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

9. The drug illustrated below:

O I Is naproxen
CH 2CH 2 C CH 3 II Must be metabolically converted into 6-
methoxy-2-naphthaleneacetic acid before it can
H 3C
O function as an anti-inflammatory agent
III Produces very little stomach upset because it is
not acidic
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

10. The drug illustrated below:

I Is a prodrug that must be metabolized to salicyclic acid
F OH before becoming active
II Is a potent antipyretic agent used to reduce fever
F CO2H
III Is used primarily for treating pain and arthritis
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

11. The drug illustrated below:

H CH 3 I Is used to treat cough
N Br II Has little affinity for μ-receptors
H III Is a potent μ-antagonist

H 3CO
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
 4
12. The drug illustrated below:
O I Has a short duration of action, but a rapid onset
H C OCH2 CH3 II Is used as an analgesic during labor
H3 C N III Is an agonist at both μ- and κ-receptors
Cl

a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

13. The drug illustrated below:

O I Is metabolized more rapidly by amide hydrolysis
C S II Is an injectible local anesthetic used in dentistry
H 3CO III Is metabolized more rapidly by ester hydrolysis
HN CH 3
C O
H3 C HC Cl
H N CH2 CH2 CH 3
H
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

14. The drug illustrated below:

O I Is a derivative of the amino acid cysteine
C II Is used to deactivate toxic electrophilic metabolites of
H 3C NH
acetaminophen when natural glutathione has been depleted
H C CH2 SH
III Possesses a thiol functional group that behaves as a
CO 2H
nucleophile
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

15. The drug illustrated below:

H CH 2 CH CH2 I Is a highly addicting μ-agonist used to treat severe pain
N Cl II Is used to reverse respiratory depression caused by an
OH overdose of opioids
III Is ineffective when administered orally

HO O O
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
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16. The drug illustrated below:
I Is used as a local anesthetic in over the
H 2N counter formulations such as lozenges for
O H CH 2CH 3 treating sore throats
CH 3CH 2CH2 O COCH2CH 2 N II Is 100% ionized at all pH values
CH 2CH 3 III Is used as a local anesthetic in the eyes
Cl
during cataract surgery
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

17. The drug illustrated below:

I Can undergo metabolism by keto-reductases to
O CH 3 give a secondary alcohol
C N
II Is an aryl acetic acid NSAID
CH 2CO2 Na III Is used to treat arthritis
H 3C
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

18. The drug illustrated below:

Cl I Is an opiate
H Cl II Belongs to the lidocaine class of local anesthetics
N H
III Is used to treat severe pain in cancer patients
N
N
H Cl
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

19. The drug illustrated below:

I Is not a μ-agonist because it lacks the 4,5-epoxy function
H
CH 3 on the morphinan system
N II Is used over the counter as a cough suppressant
CO2
H H OH III Is a potent μ-agonist used to treat severe pain
HO H
CO2H
HO
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
 6
20. The drug illustrated below:
O NH 2 I Is used to treat inflammation in the eyes
following cataract extractions
CO2 Na
II Is an inhibitor of cyclooxygenase
Br III Is a uricosuric agent used to treat chronic gout
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

21. The compound illustrated below:

CO 2H I Is released from phospholipids as needed by the action of
phospholipase A2
II Is a substrate for cyclooxygenase
III Is converted in the body into leukotrienes by the action of
5-lipoxygenase
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

22. The drug illustrated below:

I Is a potent analgesic with diminished potential for causing
H CH 2 respiratory depression
N Cl
II Is an agonist at κ-receptors and a partial antagonist at μ-
OH receptors
III Would be expected to be most effective when
administered orally
HO O OH
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
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23. The drug illustrated below:
H CH 2 CH 3 I Is an aryl acetic acid NSAID
O N
CH 2CH 2 N II Undergoes rapid metabolism by amide hydrolysis
CH 2 CH 3 III Is used as a topical local anesthetic
CH 2CH2 CH 2 CH 3
N O
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

24. The drug illustrated below:

HO I Is a pro-drug
II Is metabolized by bacteria in the colon to
N CO2 Na
Na O 2C N two molecules of 5-aminosalicyclic acid
III Has no known activity due to the charged
OH
carboxylate groups
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer

25. The drug illustrated below:

O I Is rapidly metabolized to an inactive ketone at the 16-
O CH3 position
O
II Is an analog of PGE2
HO CH3 III Is used to prevent against gastric ulcers
HO
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
 8
Section B. On the line to the right of each of the following structures write the letter
corresponding to its generic name (shown at bottom of page). (10 Points).

Cl

C O
CO2 H
N
O N OH CH 3
H 3C
HN S N O
N O CH2 CO 2H

O
O H CH 2CH3
H2 N COCH 2CH 2 N O
CH 2CH3 CO2 H
Cl OH
Cl
H CH 3
H H N Cl
H CH 2 C
N C CH 3 OH
H3 C
HO CH 3
H 3C
HO O O
CH 3
H 3C N
N HO NH
C O
O H 3C
CH 3O
OCH3
CH 3O CH 3
O
H
N C
CH3 O N
H
CH 3 CH2 CH2 CH 2CH 3
O Cl
H HN C CH 3
O

A. Salsalate F. Pentazocine K. Balsalazide

B. Acetaminophen G. Indomethacin L. Ropivacaine
C. Chloroprocaine H. Bupivacaine M. Choline Salicylate
D. Oxycodone I. Antipyrine N. Sulindac
E. Colchicine J. Oxymorphone O. Sulfasalazine
Section C. For each of the following answer the questions pertaining to the metabolism of the
drugs shown in the boxes. You will be awarded 1 point for each correct metabolite and will lose
1 point for each incorrect metabolite. (10 Points).

1. On the line, write the letter(s) corresponding to all likely phase I metabolic
pathways for the drug shown in the box below.

CH3
N
CO2 H CH3
N
H CO2 CH3
O
H
H
O OH
B H
A
CH3
CH3 N
N CO2 CH3
CO2 CH3 C OH
H
H O
O H
O
H
O

D
E
CO2 CH3
H H
N NH O
CO2 CH3 H 3C
H
H O

O
H
O

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2. On the line, write the letter(s) corresponding to all likely phase I metabolic
pathways for the drug shown in the box below.

O O
S CH 3 O O
N
NH 2 S CH 3
N
H
OH O N S
CH 2OH
B OH O N
A

O O
O O
S CH 3
N S CH 3
H C N
H
N S
CH 3 N S
OH O N CO2 H
OH O N

D
E
O O
S H
O O N
H
S CH 3 N S
N CH 3
OH OH O N

OH O
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3. On the line, write the letter(s) corresponding to all likely phase I metabolic
pathways for the drug shown in the box below.

H3 C O OH
N C C CH2 CH2 N
H3 C OH
H3 C O OH
N C C CH2 CH2 N
Cl
H3 C

B Cl
A
OH

H O OH
C N C C CH2 CH2 N
H3 C O OH
N C C CH2 CH2 N H3 C
H3 C
Cl
Cl
D
E

O OH
HO C C CH2 CH2 N
H3 C O
N C C CH2 CH 3
H3 C
Cl

Section D. For each of the following drugs write on the appropriate lines the principal
medicinal use and the mechanism of action associated with that use. (10 Points).

1.
Medicinal Use:
O
O H C OCH3
H3CO C CH2CH 2 N
N C CH2 CH 3
Cl Mechanism:
O
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2.
Medicinal Use:

O
Mechanism:
N
O N
S CH 2CH2
O

3.
Medicinal Use:
CH 3
O
H
N C
N
H Mechanism:
CH 3 CH3
Cl

4.
Medicinal Use:
H CH 2
N
Cl
Mechanism:
OH

HO O CH 2

5.
Medicinal Use:
CH 3

CH 3 CO2H
Mechanism:
H3 C
 13
Section E. For each of the following systematic names, draw the correct chemical
structure, including stereochemistry wherever indicated. Partial credit will be given but you
will lose points for incorrect chemical symbols, hydrogens missing from heteroatoms, hydrogens
missing from carbons labeled C, and for having too many bonds to an atom. (20 Points).

1. N-(2-Chloro-6-methylphenyl)-3-[2,3,4,4a,5,6,7,7a-octahydro-1H-cyclopenta[b]pyridine-
1-yl]propanamide, trans-

2. Morphinan-6-one, 7,8-didehydro-4,5-epoxy-3-hydroxy-17-methyl-14-(pentylamino)-,
(5α)-

3. 4-Piperidinecarboxylic acid, 3-methyl-4-[(1-oxopropyl)phenylamino]-1-(2-phenylethyl)-,

methyl ester, cis-

4. 2H-Thieno[2,3-e][1,2]thiazine-3-carboxamide, 6-chloro-4-hydroxy-2-methyl-N-2-
pyridinyl-, 1,1-dioxide