PSC G100 Medicinal Chemistry Exam Questions – 2006

1. A pharmacophore consists of

a. scaffold
b. core
c. conformation
d. a and b
e. a, b, and c

2. Which electrostatic interaction is strongest?

a. van der waals

b. ionic
c. hydrogen-bonding
d. ion-dipole
e. vant-hoff

3. Which electrostatic interaction is the weakest?

a. van der waals

b. ionic
c. hydrogen-bonding
d. ion-dipole
e. vant-hoff

For questions 4-6 :

O
O O
O
S
H O N N
H
H
O OH
NH2

4. How many chiral centers are present?

a. 5
b. 3
c. 2
d. 6
e. 4
5. Which best describes what functional groups are present

a. amine
b. amine, ether
c. carbamate, alcohol, sulfonamide
d. amine, carbamate, alcohol
e. b and c

6. The compound above, darunavir, is an HIV-protease inhibitor. Suppose the isobutyl

group, CH2CH(CH3)2, of the compound binds to a hydrophobic pocket in the enzyme.
Imagine that the enzyme mutates where an aspartic acid amino acid
NHCH(CH2COOH)COOH is placed in this hydrophobic pocket and binding affinity is
lost.

What would be the best group to replace the isobutyl group of darunavir in the hope of
obtaining binding to the mutated enzyme.

a. phenyl
b. CH2CH2F
c. CH2CH2NHCH3
d. CH2CH2OCH3
f. CH2SO2CH3

7. Aspirin (pKa = 3.5) will exist as a salt in which medium.

O

OH

a. stomach pH = 2
b. urine pH = 6
c. blood pH = 7
d. a and c
e. b and c

8. To decrease the acidity of aspirin (make it less acidic), which functional group would
be BEST to add on the phenyl ring relative to the carboxylic acid.

a. p-NO2 (σ = 0.78)
b. m-F (σ = 0.337)
c. p-OH (σ = -0.37)
d. p-COOH (σ = 0.45)
e. p-N(CH3)2 (σ = -0.83)
9. The logP of prozac at pH 7.0 is 2.0. To increase the water solubility of prozac at pH 7
which functional group would be BEST to add.

a. COOH
b. NH2
c. OH
d. F
e. b and c

10. Which compound would be predicted to be most soluble in water at pH 7.

a. acetazolamide logP = -0.53

b. ketoconazole logP = 3.48
c. caffeine logP = -0.10
d. thalidomide logP = 0.64
e. ampicillin logP = -1.33

11. Which compound would be predicted to be most lipophilic?

a. acetazolamide logP = -0.53

b. ketoconazole logP = 3.48
c. caffeine logP = -0.10
d. thalidomide logP = 0.64
e. ampicillin logP = -1.33

12. We discussed the following two compounds in the lecture.

H3C H3C
H H
HS HS
N N
O O
HOOC HOOC

These two compounds are

a. diastereomers
b. enantiomers
c. conformational isomers
d. identical
e. constitutiuonal isomers
13. The rate of an enzymatic reaction depends on

a. [substrate]
b. [enzyme]
c. catalyst
d. a and b
e. a and c

14. From the substrate saturation curve

the concentration of the substrate at 1/2Vmax is described as

a. [S]
b. IC50
c. Km
d. Ki
e. Bmax

15. Which of the following is used to determine Km and Vmax.

a. Pseudo-Hill Plot
b. Furchgott Analysis
c. Schild Plot
d. Lineweaver-Burk Plot
e. Scatchard Plot
16. Which enzyme-substrate pair forms the tightest ES complex

a. acetylcholineesterase-acetylcholine Km = 9 x 10-5M
b. catalase-hydrogen peroxide Km = 1.1M
c. fumarase-fumarate Km = 5 x 10-6M
d. HIV protease-darunavir Km = 5.5 x 10-5M
e. carbonic anhydrase-carbon dioxide Km = 0.012M

17. Which is the best substrate for liver alcohol dehydrogenase.

a. isopropanol kcat/Km = 64 M-1s-1

b. 3-pentanol kcat/Km = 1400 M-1s-1
c. (S)-2-butanol kcat/Km = 740 M-1s-1
d. (R)-2-pentanol kcat/Km = 32 M-1s-1
e. (S)-2-octanol kcat/Km = 8444 M-1s-1

18. Which is the best drug to reduce hypertension by inhibiting the enzyme ACE.

a. captopril ki = 14.4 nM
b. fosinoprilat ki = 0.48 nM
c. enalaprilat ki = 0.18 nM
d. lisinopril ki = 1.96 nM
e. relax

19. Of the types of enzyme inhibition discussed, which one was considered the most
important.

a. transition-state analog
b. affinity label
c. noncompetitive reversible inhibitor
d. competitive reversible inhibitor
e. competitive irreversible inhibitor

20. If an inhibitor increases the Km of an enzyme, which best describes the type of
inhibition.

a. competitive
b. noncompetitive
c. uncompetitive
d. suicide
e. irreversible