medicinal chemistry exam 2
TRANSCRIPT
1
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:
CO2H
O
CH3O
I Irreversibly inhibits cyclooxygenase
II Undergoes metabolic hydrolysis to salicyclic acid
III Is an organic acid that can irritate the stomach
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:
NC
O
OHCH2CH2
H
Cl
CCN
I Can readily enter the CNS because it is non-polar
II Is used primarily as an analgesic during childbirth
III Is administered with atropine for control of diarrhea
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:
O
N
CH3
H
H
H3CO OH
H2PO4
I Has good antitussive activity
II Can undergo metabolic conversion into morphine
III Has no affinity for μ-receptors because of the 7,8-
double bond
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
2
4. The drug illustrated below:
H2N COCH2CH2
O
N
CH2CH3
CH2CH3H
Cl
I Is susceptible to environmental oxidation at the
amino group and should be stored under nitrogen
II Is metabolized rapidly by ester hydrolysis
III Is usually administered together with atropine to
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:
HN
CO2HCH3
CH3
I Is likely to cause methemoglobinemia in susceptible
patients
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:
H2CN
CH3
CH3
H
HOH3CO
H
Cl
I Is a cis-1,2-disubstituted cyclohexane derivative
II Contains the necessary pharmacophore for a μ-agonist
and is used to treat pain
III Is a trans-1,2-disubstituted cyclohexane derivative
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:
CH2CH2 N
CH2OCH3
N C
O
CH2CH3
HS
CH2CO2
HO CO2H
CH2CO2H
I Is a salt of citric acid
II Is an extremely potent analgesic
III Can be used to induce and maintain
anesthesia during surgery
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:
S
N
NNH3C
CH3
CH3
CH3Cl
I Can be used at high doses as an antidote to cyanide
poisoning
II Is used at high doses for treating
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:
OH3C
CH2CH2 C
O
CH3
I Is naproxen
II Must be metabolically converted into 6-
methoxy-2-naphthaleneacetic acid before it can
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:
F
F OH
CO2H
I Is a prodrug that must be metabolized to salicyclic acid
before becoming active
II Is a potent antipyretic agent used to reduce fever
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:
N
CH3
H
H3CO
H
Br
I Is used to treat cough
II Has little affinity for μ-receptors
III Is a potent μ-antagonist
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:
NC
O
OCH2CH3H3C
H
Cl
I Has a short duration of action, but a rapid onset
II Is used as an analgesic during labor
III Is an agonist at both μ- and κ-receptors
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:
SCH3CO
O
CH3HN
CHC
OH3C
N CH2CH2CH3
H
H
Cl
I Is metabolized more rapidly by amide hydrolysis
II Is an injectible local anesthetic used in dentistry
III Is metabolized more rapidly by ester hydrolysis
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:
NH
CH CH2SH
CO2H
C
O
H3C
I Is a derivative of the amino acid cysteine
II Is used to deactivate toxic electrophilic metabolites of
acetaminophen when natural glutathione has been depleted
III Possesses a thiol functional group that behaves as a
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:
O
N
CH2
OH
HO O
H
Cl
CH CH2
I Is a highly addicting μ-agonist used to treat severe pain
II Is used to reverse respiratory depression caused by an
overdose of opioids
III Is ineffective when administered orally
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
5
16. The drug illustrated below:
O COCH2CH2
O
N
CH2CH3
CH2CH3H
Cl
CH3CH2CH2
H2N
I Is used as a local anesthetic in over the
counter formulations such as lozenges for
treating sore throats
II Is 100% ionized at all pH values
III Is used as a local anesthetic in the eyes
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:
C
O
H3C
N
CH3
CH2CO2Na
I Can undergo metabolism by keto-reductases to
give a secondary alcohol
II Is an aryl acetic acid NSAID
III Is used to treat arthritis
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:
NH
HN
N
Cl
Cl
H
Cl
I Is an opiate
II Belongs to the lidocaine class of local anesthetics
III Is used to treat severe pain in cancer patients
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:
N
CH3
H
HO
H
CO2
H OH
CO2H
HO H
I Is not a μ-agonist because it lacks the 4,5-epoxy function
on the morphinan system
II Is used over the counter as a cough suppressant
III Is a potent μ-agonist used to treat severe pain
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
Br
NH2
CO2 Na
I Is used to treat inflammation in the eyes
following cataract extractions
II Is an inhibitor of cyclooxygenase
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:
CO2H
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:
O
N
CH2
OH
HO OH
H
Cl
I Is a potent analgesic with diminished potential for causing
respiratory depression
II Is an agonist at κ-receptors and a partial antagonist at μ-
receptors
III Would be expected to be most effective when
administered orally
a) I only
b) III only
c) I and II only
d) II and III only
e) I, II, and III Answer
7
23. The drug illustrated below:
N OCH2CH2CH2CH3
OHN
CH2CH2 N
CH2CH3
CH2CH3
I Is an aryl acetic acid NSAID
II Undergoes rapid metabolism by amide hydrolysis
III Is used as a topical local anesthetic
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:
CO2
OH
NN
HO
O2CNa
Na
I Is a pro-drug
II Is metabolized by bacteria in the colon to
two molecules of 5-aminosalicyclic acid
III Has no known activity due to the charged
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:
HO
OO
O
CH3
HO CH3
I Is rapidly metabolized to an inactive ketone at the 16-
position
II Is an analog of PGE2
III Is used to prevent against gastric ulcers
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).
H2N COCH2CH2
O
N
CH2CH3
CH2CH3H
ClCl
HN C
OCH3
CH3
NH
CH2CH2CH2CH3Cl
O
N
CH3
OH
HO O
H
Cl
N
H
CH3
H3C
H
HO
CH2 C
C
H3C
CH3
H
O
O
OHCO2H
CO2H
OHN
NSHN
O
ON
N
C O
Cl
OH3C
CH3
CH2CO2H
HO NH
C
H3C
O
NN
CH3
O
H3C
CH3O
CH3O OCH3
O
CH3O
HNH C
O
CH3
A. Salsalate
B. Acetaminophen
C. Chloroprocaine
D. Oxycodone
E. Colchicine
F. Pentazocine
G. Indomethacin
H. Bupivacaine
I. Antipyrine
J. Oxymorphone
K. Balsalazide
L. Ropivacaine
M. Choline Salicylate
N. Sulindac
O. Sulfasalazine
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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.
A
B
C
DE
N
CH3
CO2CH3
H
H
O
O
N
CH3
CO2H
H
H
O
O
N
CH3
CO2CH3
H
H
OH
N
CH3
CO2CH3
H
H
O
O
NHH3C
CO2CH3
H
H
O
O
N
H
CO2CH3
H
H
O
O
OH
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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.
AB
C
DE
NS
O OCH3
HN
OOH N
SCH3
NS
O OCH3
NH2
OOH
NS
O OCH3
HN
OOH N
SCH2OH
NS
O OCH3
HN
OOH N
SCO2H
NS
O OH
HN
OOH N
SCH3N
S
O OCH3
OH
OOH
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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.
AB
C
DE
NOH
CH2CH2CCN
O
H3C
H3C
Cl
NOH
CH2CH2CCN
O
H3C
H3C
ClN
OHCH2CH2CCN
O
H3C
H3C
Cl
NOH
CH2CH2CCN
O
H3C
H
Cl
NOH
CH2CH2CCHO
O
Cl
OH
OH
CH2CH3CCN
O
H3C
H3C
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.
C CH2CH2 N
C
N C
O
CH2CH3
H
Cl
O
H3CO
OOCH3
Medicinal Use:
Mechanism:
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2.
N
N
O
O
CH2CH2S
O
Medicinal Use:
Mechanism:
3.
HN C
OCH3
CH3
NH
CH3Cl
Medicinal Use:
Mechanism:
4.
O
N
CH2
OH
HO CH2
H
Cl
Medicinal Use:
Mechanism:
5.
CO2H
CH3
H3C
CH3
Medicinal Use:
Mechanism:
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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