Medicinal chemistry exam 2

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



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


2


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



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



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



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


3


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



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



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



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


4


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



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



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



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


5


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



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



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



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


6


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


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



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


7


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



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



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


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

9

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

10



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

11



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:

12

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:

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

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Medicinal chemistry exam 2