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) The drug illustrated below: CO2 H I Irreversibly inhibits cyclooxygenase II Undergoes metabolic hydrolysis to salicyclic acid III Is an organic acid that can irritate the stomach O
1.
O
a) b) c) d) e)
CH3
I only III only I and II only II and III only I, II, and III
Answer
The drug illustrated below is:
2.
O H N C C CH2CH2
C OH
I II III
Can readily enter the CNS because it is non-polar Is used primarily as an analgesic during childbirth Is administered with atropine for control of diarrhea
N
Cl
a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
Answer
The drug illustrated below: I Has good antitussive activity H CH3 H PO N 2 4 II Can undergo metabolic conversion into morphine III Has no affinity for μ-receptors μ-receptors because of the 7,8H double bond
3.
H 3C O
a) b) c) d) e)
O
OH
I only III only I and II only II and III only I, II, and III
Answer 1
2 The drug illustrated below:
4.
O H2N
H CH 2CH3
CO CH 2CH 2 N Cl
a) b) c) d) e) 5.
CH 2CH3
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
I only III only I and II only II and III only I, II, and III
Answer
The drug illustrated below: CO2H I Is likely to cause methemoglobinemia in susceptible CH3 patients H N CH3 II Is a salicylate NSAID III Is used to treat mild to moderate pain a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
Answer
The drug illustrated below: CH3 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
6.
HO H 3CO
a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
Answer
The drug illustrated below:
7. S
H
CH2OCH 3
CH2CH2 N N C CH2CH3 O HO
CH2CO2
I Is a salt of citric acid II Is an extremely potent analgesic III Can be used to induce and maintain anesthesia during surgery
C O2H CH2CO2 H
a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
Answer
3 The drug illustrated below:
8.
N H 3C
N CH3
a) b) c) d) e)
S
N Cl
CH3
CH3
I only III only I and II only II and III only I, II, and III
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
Answer
The drug illustrated below:
9.
O CH2CH2 C H 3C
O
CH3
I Is naproxen II Must be metabolically converted into 6methoxy-2-naphthaleneacetic acid before it can function as an anti-inflammatory agent III Produces very little stomach upset because it is not acidic
a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
a) b) c) d) e)
The drug illustrated below: I Is a prodrug that must be metabolized to salicyclic acid 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 I only III only I and II only II and III only Answer I, II, and III
10. F
Answer
The drug illustrated below: I Is used to treat cough H CH3 N II Has little affinity for μ-receptors Br μ-antagonist III Is a potent μ-antagonist H
11.
H 3CO
a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
Answer
4 12.
H3C
The drug illustrated below: O I H C OCH2 CH3 II N III
Has a short duration of action, but a rapid onset Is used as an analgesic during labor Is an agonist at both μμ- and κ -receptors -receptors
Cl
a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
Answer
The drug illustrated below: O I Is metabolized more rapidly by amide hydrolysis S C II Is an injectible local anesthetic used in dentistry H 3CO III Is metabolized more rapidly by ester hydrolysis
13.
HN C O H3C HC
CH 3 Cl
H N CH2CH2CH3 H
a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
Answer
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 CH2SH III Possesses a thiol functional group that behaves as a CO2H nucleophile a) I only b) III only c) I and II only d) II and III only Answer e) I, II, and III
14.
The drug illustrated below: I Is a highly addicting μ-agonist used to treat severe pain H CH2 CH C H2 N II Is used to reverse respiratory depression caused by an Cl overdose of opioids OH III Is ineffective when administered orally
15.
HO
a) b) c) d) e)
O
O
I only III only I and II only II and III only I, II, and III
Answer
5 The drug illustrated below:
16.
H2N O CH3CH 2CH2
H CH2CH3
C OC H2CH2 N
O
Cl
a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
CH2CH3
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
Answer
The drug illustrated below:
17.
O C
CH 3 N CH2CO 2
Na
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
H 3C
a) b) c) d) e) 18.
I only III only I and II only II and III only I, II, and III
Answer
The drug illustrated below: I Is an opiate Cl Cl II Belongs to the lidocaine class of local anesthetics H H N III Is used to treat severe pain in cancer patients N
N H
a) b) c) d) e)
Cl
I only III only I and II only II and III only I, II, and III
Answer
The drug illustrated below: I Is not a μ-agonist μ-agonist because it lacks the 4,5-epoxy function CH3 on the morphinan system H N II Is used over the counter as a cough suppressant CO2 III Is a potent μ-agonist μ-agonist used to treat severe pain H H OH
19.
HO
H CO2H
HO
a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
Answer
6 The drug illustrated below:
20.
O
NH2 CO 2 Na
Br
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) b) c) d) e)
I only III only I and II only II and III only I, II, and III
a) b) c) d) e)
The compound illustrated below: CO2H I Is released from phospholipids as needed by the action of phospholipase A 2 II Is a substrate for cyclooxygenase III Is converted in the body into leukotrienes by the action of 5-lipoxygenase I only III only I and II only II and III only Answer I, II, and III
21.
Answer
The drug illustrated below: I Is a potent analgesic with diminished potential for causing H CH2 respiratory depression N Cl μII Is an agonist at κ -receptors and a partial antagonist at μOH receptors III Would be expected to be most effective when administered orally
22.
HO
a) b) c) d) e)
O
OH
I only III only I and II only II and III only I, II, and III
Answer
7 The drug illustrated below:
23.
H N
O
I II III
CH 2 CH3 CH2CH 2 N CH 2 CH3
N
a) b) c) d) e)
O
Is an aryl acetic acid NSAID Undergoes rapid metabolism by amide hydrolysis Is used as a topical local anesthetic
CH 2CH2 CH2 CH3
I only III only I and II only II and III only I, II, and III
Answer
The drug illustrated below:
24.
HO
Na
O 2C
N
N
CO2 Na OH
a) b) c) d) e)
I only III only I and II only II and III only I, II, and III
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
Answer
The drug illustrated below:
25.
O O
O HO
CH3
CH3
I Is rapidly metabolized to an inactive ketone at the 16position II Is an analog of PGE 2 III Is used to prevent against gastric ulcers
HO
a) b) c) d) e)
I only III only I and II only II and III only 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
CO 2H
N O HN N
OH
N N
S
CH 3
H3C
O CH2CO 2H
O
O
O
H CH 2CH3
CO CH 2CH 2 N
H2N
Cl
Cl
O CH 2CH3
CO 2 H
OH
CH3
H H
H H
CH2
N
Cl
C
N
C
OH
CH3
H3 C
HO
CH3 H 3C
HO
O
O
CH 3 H 3C
N N
NH
HO
C O H 3C
O CH3O
OCH3
CH 3O
CH 3 O H N C
CH3 O O
CH 3 H
HN
C CH3
H
N CH 2CH2CH2CH 3
Cl
O
A. B. C. D. E.
Salsalate Acetaminophen Chloroprocaine Oxycodone Colchicine
F. G. H. I. J.
Pentazocine Indomethacin Bupivacaine Antipyrine Oxymorphone
K. L. M. N. O.
Balsalazide Ropivacaine Choline Salicylate Sulindac 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 Points). 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.
CH 3 N CO 2 H
CH3 N
H
CO 2 CH3 O
H
H O
OH H
B A
CH3 N
CH 3
CO 2 CH3
N CO 2 CH3
C
OH
H
H
O O
H
H
O
O
D E CO 2 CH 3 H
H
N H 3C
CO 2 CH3 H O H
O
9
NH
O H
O
10 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
CH3
N
O S
NH 2 OH
N
CH3 H N
O OH
B
O
O
S
N
S CH 2OH
A
O
O
N
O
CH3
S
C
H N
O N
CH3 H N
S CH 3
OH
O
CO 2 H
N
OH
O S
S
O N
N
H N
S
O N
H
CH3 OH
OH
O
D
E
O
S
O
CH 3 OH
O
N
11 3. On the line, write the letter(s) corresponding to all likely phase I metabolic pathways for the drug shown in the box below.
O
H3C
OH
N C C CH2CH2
N
H3C
OH
OH
N C C CH2CH 2
Cl
B
Cl OH
H
C
O
O
OH
N C C CH2CH2
OH
N C C CH2CH2
N
H3C
A
H3C
O
H3C
N
H3C
N
H3C Cl Cl
D
E
O H3C
HO C C CH2 CH2
O
OH N
N C C CH2CH3 H3C
Section D.
Cl
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 CH2CH2 N Cl
N C CH2CH3 O
Mechanism:
12 2. Medicinal Use:
O
Mechanism:
N N
O S CH 2CH2
O
3. Medicinal Use: CH 3 O H N C H
CH 3
N CH3
Mechanism:
Cl
4. Medicinal Use: H
CH 2 N
Cl
Mechanism:
OH
HO
O
CH 2
5. Medicinal Use: CH3 CH3 H3C
CO2 H
Mechanism:
13 Section E. For each of the following systematic names, draw the correct chemical structure, 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]pyridine1-yl]propanamide, trans-
2. Morphinan-6-one, 7,8-didehydro-4,5-epoxy-3-hydroxy-17-methyl-14-(pentylamino)-, (5α)(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-2pyridinyl-, 1,1-dioxide
