Patrick TB Ch22

Patrick: An Introduction to Medicinal Chemistry 3e
Chapter 22: Antiulcer agents

Type: multiple choice question
Title: Chapter 22 Question 01
01) Which o the ollo!in" a"ents does not aect the release o "astric acid rom parietal cells#
Feedback: Acetylcholine$ "astrin and histamine %ind to their respecti&e receptors on parietal cells to
induce the release o "astric acid' (oradrenaline does not do this'
Page reference: )*2+)*3
a' Acetylcholine
,%' (oradrenaline
c' -astrin
d' .istamine
Type: matching question
Title: Chapter 22 + Question 02
02) /he structure o histamine is sho!n %elo!' What la%els are used to distin"uish the nitro"ens at
positions A$ 0 and C#
Feedback: /he +nitro"en is the one at the end o the side chain on histamine' /he nitro"en is the
one in the imida1ole rin" closest to the side chain' /he nitro"en is the imida1ole nitro"en urthest
a!ay rom the side chain'
Page reference: )**
a' A 2
%' 0 2
c' C 2
03) What sort o heterocyclic rin" is present in histamine#
Feedback: /he rin" systems "i&en are as ollo!s
Page reference: )**
a' Imida1olidine
%' Pyridine
c' Pyrrole
,d' Imida1ole
Title: Chapter 22 Question 0*
0*) What type o histamine receptor is associated !ith the dilation o %lood &essels#
Feedback: /here are t!o main types o histamine receptor$ .1 and .2' .3 and .* receptors do not
e3ist' /he .1 receptor is tar"eted %y traditional antihistamines !hile the .2 receptor is tar"eted %y
histamine anta"onists used in anti+ulcer therapy'
Page reference: )**+)*4
,a' .1
%' .2
c' .3
d' .*
OXFORD H i g h e r E d u c a t i o n
5 63ord 7ni&ersity Press$ 200)' All ri"hts reser&ed'
04) Which ailment is not treated %y con&entional histamine anta"onists actin" on the .1 receptor#
Feedback: Anti+ulcer a"ents actin" as histamine anta"onists tar"et .2+receptors on parietal cells'
a' .ay e&er
%' Insect %ites
,c' 7lcers
d' Asthma
Title: Chapter 22 Question 0)
0)) /here are t!o possi%le tautomers or histamine'
/automer A is more sta%le than tautomer 0' Why#
Feedback: /he side chain is electron !ithdra!in" due to the positi&ely char"ed ammonium "roup at the
end o the chain' 8ince this is an inducti&e eect$ it is elt more at the nitro"en than the nitro"en since
the ormer is nearer the side chain' Inducti&e eects decrease !ith the num%er o %onds in&ol&ed' /his
means that the nitro"en is "oin" to %e less %asic and less likely to use its lone pair o electrons to orm
a %ond to hydro"en'
Page reference: )42+)43
,a' /he side chain has an inducti&e electron !ithdra!in" eect on the rin" makin" the nitro"en less
%asic than the nitro"en'
%' /he side chain has an inducti&e electron donatin" eect on the rin" makin" the nitro"en less %asic
than the nitro"en'
c' /he side chain has an inducti&e electron !ithdra!in" eect on the rin" makin" the nitro"en less
%asic than the nitro"en'
d' /he side chain has an inducti&e electron donatin" eect on the rin" makin" the nitro"en less %asic
than the nitro"en'
09) /here are t!o possi%le tautomers or histamine'
What !ould %e the eect on the tautomer population i a methyl "roup !ere to %e placed at position * o
the rin"#
Feedback: /he methyl "roup has an inducti&e eect !hich is electron donatin"' /he nitro"en is closer
to this su%stituent than the nitro"en and so the nitro"en e3periences this inducti&e eect to a "reater
e3tent' /his makes the nitro"en more %asic and more likely to use its lone pair o electrons to %ond to
hydro"en'
Page reference: )43
a' /he relati&e population o 0 !ould increase'
%' /here !ould %e no dierence'
,c' /he relati&e population o A !ould increase'
d' It is not possi%le to predict the eect'
Title: Chapter 22 Question 0:
0:) /here are t!o possi%le tautomers or histamine' A methyl "roup at position * plays an important role
in a&ourin" tautomer A throu"h an inducti&e eect'
What other important eect arises rom the presence o a methyl "roup at position *#
Feedback: It introduces selecti&ity or the .2 receptor and is present in anti+ulcer dru"s such as
cimetidine'
Page reference: )43
a' It introduces selecti&ity or the .1 receptor'
,%' It introduces selecti&ity or the .2 receptor'
c' It protects the molecule rom meta%olism'
d' It increases the a%ility o the compound to cross cell mem%ranes'
Title: Chapter 22 Question 0;
0;) What eect does histamine ha&e on the release o "astric acid#
Feedback: .istamine interacts !ith histamine .2 receptors to increase "astric acid secretion'
Page reference: )*3
,a' It increases secretion
%' It decreases secretion
c' It has no eect
d' It completely s!itches o secretion
10) What eect !ould a histamine .2 anta"onist ha&e on the release o "astric acid#
Feedback: An .2 anta"onist !ould pre&ent histamine acti&atin" the .2 receptor and so "astric acid
secretion !ould decrease' It !ould not %e stopped completely since "astric acid and acetylcholine are
still a%le to stimulate "astric acid secretion'
Page reference: )*3+)**
a' It !ould increase secretion
,%' It !ould decrease secretion
c' It !ould ha&e no eect
d' It !ould stop secretion completely
11) N +-uanylhistamine is a partial a"onist at the .2 receptor' What is meant %y a partial a"onist#
a' /he structure is !eakly %ound to the receptor %indin" site'
Feedback: incorrect' /his only states that the structure is %indin" to the receptor and does not identiy
!hether this %indin" is associated !ith a"onist or anta"onist acti&ity'
Page reference: )*)+)*:
%' /he structure only occupies a portion o the receptor %indin" site'
Feedback: incorrect' /his only states that the structure is %indin" to the receptor and does not identiy
!hether this %indin" is associated !ith a"onist or anta"onist acti&ity'
,c' /he structure is %ound to the receptor %indin" site %ut does not ully acti&ate the receptor'
Feedback: Correct' /his is the most accurate description o the our'
d' /he structure %inds to the receptor$ pre&ents the natural messen"er rom %indin" and eliminates any
inherent acti&ity associated !ith the receptor'
Feedback: incorrect' /his descri%es an in&erse a"onist !hich %inds to sta%ilise an inacti&e conormation o
the receptor'
12) N+-uanylhistamine !as the irst lead compound or the de&elopment o .2+anta"onists'
What strate"y !as used in de&elopin" the "uanidine structure <A)#
Feedback: =3tension indicates the addition o a ne! unctional "roup to ind an e3tra %indin" re"ion'
.ere$ the unctional "roup is already present and has %een mo&ed urther a!ay rom the imida1ole rin"
%y chain e3tension' 8u%stituent &ariation and isosteric replacement indicate the replacement o a "roup
!ith another "roup !hich has not occurred here'
Page reference: )*;
a' =3tension
,%' Chain e3tension
c' 8u%stituent &ariation
d' Isosteric replacement
13) N+-uanylhistamine !as the irst lead compound or the de&elopment o .2+anta"onists'
What !as the rationale or the strate"y used in de&elopin" the "uanidine structure <A)#
Feedback: /he anta"onist %indin" re"ion is urther a!ay rom the imida1ole %indin" re"ion than the
a"onist %indin" re"ion' /hereore$ e3tendin" the distance %et!een the "uanyl "roup and the imida1ole
rin" increases the chances that the molecule !ill %ind as an anta"onist rather than as an a"onist'
Page reference: )*;
a' /o reduce the inducti&e eect o the "uanidine unit on the imida1ole rin"'
%' /o increase the le3i%ility o the chain %y allo!in" more sin"le %ond rotations'
c' /o mo&e the %indin" "roup closer to the a"onist %indin" re"ion and a!ay rom the anta"onist %indin"
re"ion'
,d' /o mo&e the %indin" "roup closer to the anta"onist %indin" re"ion and a!ay rom the a"onist %indin"
re"ion'
1*) >urin" the search or .2 anta"onists$ the ollo!in" %indin" theory !as proposed %et!een a
"uanidine unit and a car%o3ylate unit in the %indin" site' What !as it called#
Feedback: /he %indin" theory !as called the chelation %indin" theory and in&ol&es the "uanidine and
car%o3ylate ion interactin" throu"h ionic and hydro"en %ondin" interactions'
Page reference: )*:+)*;
a' Ionic %indin" theory
%' .ydro"en %ondin" theory
,c' Chelation %indin" theory
d' Comple3ation %indin" theory
14) /he ollo!in" structures sho! some o the important molecules leadin" to the disco&ery o structure
0'
What sort o unctional "roup has %een introduced in 8?@A ;14:1#
Feedback: /he unctional "roups descri%ed in the options are as sho!n %elo!:
a' -uanidine
%' 7rea
,c' /hiourea
d' /hioamide
1)) /he ollo!in" structures sho! some o the important molecules leadin" to the disco&ery o structure
0'
A unctional "roup has %een introduced in 8?@A ;14:1' What !as the rationale or introducin" this
unctional "roup#
Feedback: 8tructure 0 is %urimamide' /he rationale !as to replace the %asic "uanyl "roup !ith a
neutral "roup such that it !ould interact %y hydro"en %ondin" rather than ionic %ondin"' A neutral "roup
!as chosen that !as as similar as possi%le to the "uanyl "roup in terms o si1e and shape'
a' /o reduce the num%er o possi%le hydro"en %ond donors present'
,%' /o replace an ionic "roup !ith a neutral "roup'
c' /o chan"e the shape o the terminal unctional "roup'
d' /o chan"e the si1e o the terminal unctional "roup'
19) /he ollo!in" structures sho! some o the important molecules leadin" to the disco&ery o structure
0'
What !as the rationale or the strate"y used in de&elopin" structure 0 rom 8?@A ;14:1#
Feedback: 8tructure 0 is %urimamide' /he anta"onist %indin" re"ion is urther a!ay rom the imida1ole
%indin" re"ion than the a"onist %indin" re"ion' /hereore$ e3tendin" the distance %et!een the thiourea
"roup and the imida1ole rin" increases the chances that the molecule !ill %ind as an anta"onist rather
than an a"onist'
Page reference: )41
a' /o reduce the inducti&e eect o the terminal unctional "roup on the imida1ole rin"'
%' /o increase the le3i%ility o the chain %y allo!in" more sin"le %ond rotations'
c' /o mo&e the terminal unctional "roup closer to the a"onist %indin" re"ion and a!ay rom the
anta"onist %indin" re"ion'
,d' /o mo&e the terminal unctional "roup closer to the anta"onist %indin" re"ion and a!ay rom the
a"onist %indin" re"ion'
1:) /he ollo!in" dia"ram sho!s the &arious tautomers o the terminal unctional "roup in structure
cimetidine
'
Which is considered to %e the most sta%le tautomer#
Feedback: 8ince the electron !ithdra!in" eect o the cyanide "roup is inducti&e$ it is e3perienced
most %y the nitro"en directly attached to cyanide' As a result$ this nitro"en !ill %e the least %asic o the
three nitro"ens present in the "uanidine moiety and the least likely to %ond to hydro"en'
Page reference: )4)
a' /automer I
,%' /automer II
c' /automer III
d' /hey are all eBual in sta%ility
Title: Chapter 22 + Question 1;
1;) /he ollo!in" synthetic route has %een used to produce cimetidine'
What rea"ents !ere used in steps A$ 0 and C#
Feedback: Cithium aluminium hydride is a po!erul reducin" a"ent capa%le o reducin" car%onyl "roups
such as esters' =sters are reduced to primary alcohols'
.ydro"en %romide is used to con&ert an alcohol to an alkyl %romide !hich can then under"o
nucleophilic su%stitution !ith 2+aminoethanethiol'
Methylamine in ethanol is used to su%stitute the methylthio "roup in the penultimate structure !ith a
methylamino "roup'
Page reference: )49
a' 8tep A 2 Cithium aluminium hydride
%' 8tep 0 2 *:D hydro"en %romide and 2+aminoethanethiol
c' 8tep C 2 Methylamine in ethanol
20) /he ollo!in" "raph measures lo"<acti&ity) &ersus lo" P'
What is measured %y lo" P#
Feedback: Co" P measures the o&erall hydropho%icity o a molecule'
Page reference: )4:+)4;
a' 8i1e
,%' .ydropho%icity
c' 0asicity
d' >ipole moment
What does the "raph indicate a%out a urea "roup in comparison to an N+methyl urea "roup#
Feedback: Co" P is a measure o a dru"Es hydropho%icity' Increasin" &alues o lo"P indicate increasin"
hydropho%icity and so the urea "roup is more hydropho%ic than an (+methyl urea "roup'
a' /he urea "roup is smaller
%' /he urea "roup is less %asic
c' /he urea "roup is more hydropho%ic
,d' /he urea "roup is less hydropho%ic
What does the "raph sho! a%out acti&ity#
Feedback: As lo"P increases$ acti&ity increases' Co"P is a measure o hydropho%icity and so increased
acti&ity is associated !ith increasin" hydropho%icity'
,a' Acti&ity increases !ith hydropho%ic character
%' Acti&ity decreases !ith hydropho%ic character
c' Acti&ity increases !ith %asicity
d' Acti&ity increases !ith the si1e o the "roup
/he nitroketeneaminal "roup does not it the strai"ht line' Which o the ollo!in" statements is true#
Feedback: /he lo" P &alue or this "roup is relati&ely lo! and the compound should ha&e a lo!er
acti&ity than it actually has'
Page reference: )4;+))0
,a' /he acti&ity is too "reat or the hydropho%icity o the "roup'
%' /he acti&ity is too "reat or the si1e o the "roup'
c' /he acti&ity is too "reat or the %asicity o the "roup'
d' /he acti&ity is too small or the hydropho%icity o the "roup'
2*) /he ollo!in" "raph measures lo"<acti&ity) &ersus lo" P'
What physical eature other than lo"P is important to the acti&ity o cimetidine analo"ues#
Feedback: /o %e precise$ the orientation o the dipole moment is important to the acti&ity rather than the
si1e o the dipole moment'
Page reference: ))0
a' .ydropho%icity
%' 0asicity
c' Molecular !ei"ht
,d' >ipole moment
/he nitroketeneaminal "roup does not it the line o the "raph' /his "roup is present in a clinically
important anti+ulcer dru"' Identiy the dru"'
Feedback: Fanitidine has the ollo!in" structure
Page reference: ))2
,a' Fanitidine
%' Aamotidine
c' Camitidine
d' Co3tidine
2)) A Q8AF study o cimetidine analo"ues !ith dierent planar "roups produced the ollo!in" eBuationG

lo" <Acti&ity) 2 ;'12 cos H 0')lo"P +2'91'
What is the rele&ance o the cos entry#
Feedback: /he cos entry Buantiies the orientation o a dipole moment' is the de&iation in an"le o
the dipole moment rom the ideal orientation o 30
o
'
Page reference: ))0+))1
,a' It Buantiies the orientation o a dipole moment
%' It Buantiies the ma"nitude o a dipole moment
c' It Buantiies the orientation o hydro"en %onds
d' It Buantiies the stren"th o hydro"en %ondin"
29) A Q8AF study o cimetidine analo"ues !ith dierent planar "roups produced the ollo!in" eBuationG

lo" <Acti&ity) 2 ;'12 cos H 0')lo"P +2'91'
What is the ideal &alue o ?
Feedback: At 0
o
$ cos is eBual to a ma3imum &alue o 1' At any other &alue$ the cos &alue !ill %e a
raction' /his means that the calculated acti&ity !ill %e smaller'
Page reference: ))0+))1
,a' 0
o
%' *4
o
c' )0
o
d' ;0
o
2:) What en1yme catalyses the ollo!in" reaction#
Feedback: Car%onic anhydrase catalyses the ormation o car%onic acid rom !ater and car%on dio3ide'
/he acid dissociates to "i&e a proton and a hydro"en car%onate ion'
Page reference: ))4
a' Car%onic synthase
%' Car%onic li"ase
,c' Car%onic anhydrase
d' Car%onic hydrolase
2;) What reaction is catalysed to po!er the proton pump#
Feedback: .ydrolysis o A/P to A>P in&ol&es the splittin" o the terminal phosphate "roup rom the
triphosphate chain o A/P$ "eneratin" ener"y !hich can %e used to po!er the proton pump'
Page reference: ))4
,a' A/P to A>P
%' A/P to AMP
c' A/P to cyclic AMP
d' A/P to adenosine
30) /he proton pump inhi%itors are prodru"s' Where do they "et acti&ated#
Feedback: /he proton pump inhi%itors are acti&ated %y stron" acidic conditions ound only in the
canaliculae o parietal cells'
Page reference: )))
a' In the li&er
%' In the %lood supply
c' In parietal cells
,d' In the canaliculae o parietal cells
31) What is the typical pK
a
or proton pump inhi%itors#
Feedback: /he proton pump inhi%itors are !eak %ases and reBuire stron" acidic conditions %eore they
protonate and %ecome acti&ated'
Page reference: )))
,a' *
%' )
c' 9'*
d' ;
32) What conditions are reBuired to acti&ate proton pump inhi%itors#
Feedback: /he proton pump inhi%itors are !eak %ases and reBuire stron" acidic conditions %eore they
protonate and %ecome acti&ated'
Page reference: )))
,a' 8tron"ly acidic conditions
%' Weakly acidic conditions
c' (eutral conditions
d' 8li"htly %asic conditions
33) /he ollo!in" dia"ram sho!s the de&elopment o the irst commercially a&aila%le proton pump
inhi%itor omepra1ole <A)

What sort o heterocyclic rin" !as introduced in .12*I)#
Feedback: /he &arious rin"s descri%ed are sho!n %elo!' /he term imida1o%en1ene is incorrect and is
not a reco"nised term'
Page reference: ))9
a' Quina1oline
%' Imida1o%en1ene
,c' 0en1imida1ole
d' Indole
3*) /he ollo!in" dia"ram sho!s the de&elopment o the irst commercially a&aila%le proton pump
inhi%itor omepra1ole <A)' >urin" this study$ timopra1ole !as ound to %e a promisin" lookin" candidate'
Addition o methyl and metho3y su%stituents to the pyridine rin" increases the acti&ity o timopra1ole'
What eect do these "roups ha&e#
Feedback: /he acti&ation o the dru" under acidic conditions reBuires the pyridine nitro"en to act as a
%ase' /he addition o electron donatin" su%stituents increases the %asicity o the pyridine nitro"en'
Page reference: )):
a' /hey it into hydropho%ic %indin" pockets in the acti&e site and increase %indin" stren"th'
,%' /hey are electron donatin" "roups and increase the %asicity o the pyridine rin"'
c' /hey act as steric shields to pre&ent meta%olism at e3posed re"ions o the pyridine rin"'
d' /hey %lock the dru" %indin" to alternati&e tar"ets'
34) /he ollo!in" dia"ram sho!s the de&elopment o the irst commercially a&aila%le proton pump
inhi%itor omepra1ole <A)' >urin" this study$ it !as ound that the methyl and metho3y su%stituents on the
pyridine rin" had an important role in increasin" acti&ity' What eect !ould you predict i the pyridine
su%stituents in omepra1ole <A) !ere placed as sho!n %elo!#
Feedback: /he metho3y su%stituent can interact !ith the pyridine rin" %y resonance' When the
su%stituent is located at the para position$ a resonance structure can %e dra!n !here a ne"ati&e char"e
is placed on the pyridine nitro"en$ thus increasin" its %asic character and the acti&ity o the compound' I
the su%stituent is at the meta position$ this resonance structure is no lon"er possi%le' /his means that
the pyridine rin" !ill %e less %asic and the structure !ill %e less acti&e'
Page reference: )):+));
a' Acti&ity !ould %e unaected
%' Acti&ity !ould increase
,c' Acti&ity !ould decrease
d' It is impossi%le to predict !hat !ould happen
3)) /he ollo!in" structure has %een marketed as the more acti&e enantiomer o a proton pump inhi%itor'
What is the name o this structure#
Feedback: /he structure sho!n is the 8+enantiomer o omepra1ole and this !as !hat led to the
structure %ein" called esomepra1ole'
Page reference: ));
a' =spantopra1ole
%' =slansopra1ole
,c' =somepra1ole
d' =sra%epra1ole
39) /he ollo!in" structure <esomepra1ole) has %een marketed as the more acti&e enantiomer o
omepra1ole'
What is the name o the strate"y !here a clinically important racemic dru" is replaced !ith the acti&e
enantiomer o the dru"#
Feedback: Chiral s!itchin" has %een used on se&eral dru"s !hich !ere pre&iously marketed as
racemates'
Page reference: ));
a' Patent s!itchin"
%' =nantiomeric s!itchin"
c' Asymmetric s!itchin"
,d' Chiral s!itchin"
Title: Chapter 22 + Question 3:
3:) /he ollo!in" dia"ram sho!s the synthetic route to an important proton pump inhi%itor'
What !ere the rea"ents used or step A and step 0
Feedback: 8odium hydro3ide con&erts the thiol to a thiolate !hich can then displace the chloride rom
the alkyl chloride &ia a nucleophilic su%stitution reaction' /he meta+chloroper%en1oic acid is an o3idisin"
a"ent !hich is oten used as an epo3idisin" a"ent$ %ut !hich in this case is used to o3idise the sulphur
atom o the penultimate compound'
Page reference: )90
a' 8tep A 2 8odium hydro3ide
%' 8tep 0 2 Meta+chloroper%en1oic acid
3;) What type o triple therapy is most commonly used to treat ulcers caused %y Helicobacter pylori#
Feedback: /he proton pump inhi%itor ser&es to reduce the Buantity o hydrochloric acid released into
the stomach %y parietal cells' /he anti%acterial a"ents are used to com%at the %acterium Helicobacter
pylori !hich is kno!n to cause inlammation and cell dama"e in the stomach'
Page reference: )92
a' An .2 anta"onist$ proton pump inhi%itor and an anti%acterial a"ent
%' An .2 anta"onist$ and t!o anti%acterial a"ents
,c' A proton pump inhi%itor and t!o anti%acterial a"ents
d' /!o proton pump inhi%itors and an anti%acterial a"ent
Title: Chapter 22 + Question *0
*0) Which o the ollo!in" structures represents histamine at physiolo"ical p.#
Feedback: /he side chain nitro"en is ully ionised and the heterocyclic nitro"ens are not ionised'
,a' 8tructure A
%' 8tructure 0
c' 8tructure C
d' 8tructure >
*1) Which nitro"en atom <or atoms) in histamine is I are considered important or .2+a"onist acti&ity %ut not
.1 acti&ity#
Feedback: /he nitro"en atom is in&ol&ed in a hydro"en %ondin" interaction !ith the .2 receptor %ut not
the .1 receptor' /he nitro"en atom is in&ol&ed in hydro"en %ondin" interactions !ith %oth the .1 and .2
receptor %indin" sites$ !hile the ionised ammonium "roup at the end o the alkyl chain is in&ol&ed in an ionic
interaction !ith %oth %indn" sites'
Page reference: )*4+)*)
a' /he nitro"en atom and the nitro"en atom
%' /he nitro"en atom
,c' /he nitro"en atom
d' /he nitro"en atom
*2) 8e&eral %indin" re"ions !ere proposed to %e present in the %indin" site o the .2 receptor' Which o the
ollo!in" statements is incorrect#
Feedback: /he imida1ole %indin" re"ion is the same or a"onists and anta"onists'
Page reference: )*4+)*)
,a' /here are t!o %indin" re"ions or the imida1ole rin" o histamine analo"ues$ one !hich is occupied %y
a"onists and one !hich is occupied %y anta"onists'
%' /here is a %indin" re"ion !hich interacts ionically !ith the +nitro"en o histamine and results in a"onist
acti&ity'
c' /here is a %indin" re"ion urther a!ay rom the imida1ole rin" that produces an anta"onist eect i
occupied'
d' /he +nitro"en o histamine can only %ind to the a"onist %indin" re"ion !hile the "uanyl "roup o N+
"uanylhistamine can %ind either to the anta"onist %indin" re"ion or the a"onist %indin" re"ion'
*3) /he ollo!in" structures are some o the important molecules leadin" to the disco&ery o cimetidine'
In !hat order !ere these compounds de&eloped#
Feedback: 8tructure C is %urimamide' 8tructure 0 is N +"uanylhistamine' 8tructures A and > are
compounds that !ere de&eloped rom N +"uanylhistamine and !hich led to the disco&ery o %urimamide'
Page reference: )*)+)4*
a' A$ 0$ >$ C
%' 0$ A$ C$ >
,c' 0$ A$ >$ C
d' 0$ >$ A$ C
Title: Chapter 22 + Question **
**) /he ollo!in" structures are some o the important molecules leadin" to the disco&ery o cimetidine'
Which o the structures sho!n is %urimamide#
Feedback: 8tructure C is %urimamide' 8tructure 0 is N +"uanylhistamine' 8tructures A and > are
compounds that !ere de&eloped rom N +"uanylhistamine and !hich led to the disco&ery o %urimamide'
a' 8tructure A
%' 8tructure 0
,c' 8tructure C
d' 8tructure >
*4) /he ollo!in" structures are some o the important molecules leadin" to the disco&ery o cimetidine'
Which o the structures sho!n is N +"uanylhistamine#
Feedback: 8tructure 0 is N+"uanylhistamine' 8tructure C is %urimamide' 8tructures A and > are
compounds that !ere de&eloped rom N+"uanylhistamine and !hich led to the disco&ery o %urimamide
a' 8tructure A
,%' 8tructure 0
c' 8tructure C
d' 8tructure >
Title: Chapter 22 + Question *)
*)) /he ollo!in" structures are some o the important molecules leadin" to the disco&ery o cimetidine'
Which o the ollo!in" statements is true#
Feedback: 8tructure 0 is N +"uanylhistamine' 8tructure C is %urimamide' 8tructures A and > are
compounds that !ere de&eloped rom N+"uanylhistamine and !hich led to the disco&ery o %urimamide'
a' 8tructure 0 !as de&eloped rom structure A usin" a chain e3tension strate"y'
%' 8tructure C !as de&eloped rom structure > usin" a %io+isostere strate"y'
c' 8tructure > !as de&eloped rom structure A usin" a chain e3tension strate"y'
,d' 8tructure C !as de&eloped rom structure > usin" a chain e3tension strate"y'
*9) /he ollo!in" structures sho! some o the important molecules leadin" to the disco&ery o structure 0'
Which o the ollo!in" statements concernin" structure 0 is untrue#
Feedback: It esta%lished that %indin" to the anta"onist %indin" re"ion in&ol&ed hydro"en %ondin" and not
ionic %ondin"'
a' It esta%lished the e3istence o .2+receptors'
%' It !as a "ood anta"onist at .2 receptors !ith no a"onist acti&ity'
c' It inhi%ited "astric acid release rom parietal cells'
,d' It indicated that %indin" to the anta"onist %indin" re"ion in&ol&ed ionic %ondin" and not hydro"en
%ondin"'
Title: Chapter 22 + Question *:
*:) Identiy the ollo!in" structures
Feedback: 0urimamide !as the irst o the our compounds named to %e de&eloped and esta%lished the
e3istence o .2 receptors' /hia%urimamide !as de&eloped %y introducin" a sulphur atom into the side chain
o %urimamide' Metiamide in&ol&ed the urther addition o a methyl su%stituent to the imida1ole rin" and
cimetidine in&ol&ed replacement o the thiourea "roup !ith cyano"uanidine "roup'
a' Cimetidine 2 8tructure 0
%' /hia%urimamide 2 8tructure C
c' Metiamide 2 8tructure >
d' 0urimamide 2 8tructure A
Title: Chapter 22 J Question *;
*;) Which o the ollo!in" structures has an electron donatin" side chain attached to the imida1ole rin"#
Feedback: /he structures sho!n <A+>) are %urimamide$ cimetidine$ thia%urimamide and metiamide
respecti&ely' 0urimamide has an electron donatin" side chain' /he other structures contain sulur in the side
chain$ makin" the su%stituent electron !ithdra!in"'
,a' 8tructure A
%' 8tructure 0
c' 8tructure C
d' 8tructure >
Title: Chapter 22 J Question 40
40) /he ollo!in" structures !ere part o a study aimed at indin" anti+ulcer a"ents' What sort o mode o
action do they ha&e#
respecti&ely' /hey all act as anta"onists at the .2 receptor'
a' /hey are receptor a"onists
,%' /hey are receptor anta"onists
c' /hey are en1yme inhi%itors
d' /hey %lock carrier proteins
41) /he ollo!in" structures !ere part o a study aimed at indin" anti+ulcer a"ents' What is their tar"et#
respecti&ely' /hey all act as anta"onists at the .2 receptor'
a' /he proton pump
%' /he .1 receptor
,c' /he .2 receptor
d' /he "astrin receptor
42) /he ollo!in" structures !ere part o a study aimed at indin" anti+ulcer a"ents' Which o the structures
has the p?
a
or the imida1ole rin"#
respecti&ely' 0urimamide has an electron donatin" side chain "i&in" it a p?a o 9'24' /he other structures
contain sulur in the side chain$ makin" the su%stituent electron !ithdra!in"' /hia%urimamide has a p?a o
)'24' Metiamide has an electron donatin" methyl "roup !hich counteracts the electron !ithdra!in" inluence
o the side chain "i&in" it a p?a o )':0' Aor the same reson$ the p?a or the imida1ole rin" o cimetidine is
also hi"her than the p?a or thia%urimamide
a' 8tructure A
%' 8tructure 0
,c' 8tructure C
d' 8tructure >
43) /he ollo!in" structures !ere part o a study aimed at indin" anti+ulcer a"ents' In !hat order !ere the
structures de&eloped#
respecti&ely'
a' C$ A$ 0$ >
%' 0$ >$ C' A
,c' A$ C$ >$ 0
d' >$ 0$ C$ A
Title: Chapter 22 + Question 4*
4*) /he ollo!in" structure is cimetidine' Which electron donatin" "roup is present to a&our the acti&e
tautomeric orm o the imida1ole rin" sho!n#
Feedback: /he methyl "roup has an inducti&e electron donatin" eect on the imida1ole rin"' /his inducti&e
eect is more pronounced at the +nitro"en than the +nitro"en since the ormer is closer to the su%stituent'
/he inducti&e eect makes the +nitro"en more %asic and a&ours the tautomer !here this nitro"en is
%onded to a hydro"en'
,a' -roup a
%' -roup %
c' -roup c
d' -roup d
44) /he ollo!in" structure is cimetidine' Which electron !ithdra!in" "roup is present to a&our the acti&e
tautomeric orm o the imida1ole rin" sho!n#
Feedback: /he sulur has an inducti&e electron !ithdra!in" eect on the imida1ole rin"' /his inducti&e
eect is more pronounced at the +nitro"en than the +nitro"en since the ormer is closer to the su%stituent'
/he inducti&e eect makes the +nitro"en more %asic and a&ours the tautomer !here this nitro"en is
%onded to a hydro"en'
a' -roup a
,%' -roup %
c' -roup c
d' -roup d
Title: Chapter 22 + Question 4)
4)) /he ollo!in" structure is cimetidine' Which "roup is present to interact !ith a hydro"en %ondin" re"ion
not used %y histamine#
Feedback: -roup d is a naturally occurrin" moiety !hich is neutral and interacts !ith a %indin" re"ion
throu"h hydro"en %ondin"' It !as used to replace a thiourea "roup in pre&ious structures since the latter
!as responsi%le or to3ic side eects'
a' -roup a
%' -roup %
c' -roup c
,d' -roup d
49) /he ollo!in" structure is cimetidine' /he "uanidine moiety at the end o the side chain is neutral !hich
is unusual since "uanidine moieties are usually %asic' Which one o the coloured "roups sho!n is
responsi%le or this#
Feedback: /he cyanide "roup has a stron" inducti&e eect !hich is electron !ithdra!in"' As a result the
%asicity o the "uanidine "roup is reduced and it is less likely to ionise'
Page reference: )4*+)44
,a' -roup a
%' -roup %
c' -roup c
d' -roup d
Title: Chapter 22 + Question 4:
4:) Which o the ollo!in" structures is a meta%olite o cimetidine#
Feedback: /he meta%olites o cimetidine are sho!n %elo!'
Page reference: )4)
,a' 8tructure A
%' 8tructure 0
c' 8tructure C
d' 8tructure >
Title: Chapter 22 + Question 4;
4;) Which o the ollo!in" structures is a meta%olite o cimetidine#
Feedback: /he meta%olites o cimetidine are sho!n %elo!'
Page reference: )4)
a' 8tructure A
%' 8tructure 0
c' 8tructure C
,d' 8tructure >
Title: Chapter 22 + Question )0
)0) /he synthetic route to cimetidine is sho!n %elo!:
Match the structures sho!n %elo! to the a%o&e synthetic route'
Feedback: /he synthesis o cimetidine is a * sta"e process in&ol&in" the construction o cimetidineEs side
chain on a startin" material already containin" the reBuired imida1ole rin"'
Page reference: )49
a' A 2 8tructure III
%' 0 2 8tructure II
c' C 2 8tructure I
d' > 2 8tructure IK
)1) /he ollo!in" conormation or the cyano"uanidine "roup o cimetidine is not a&oured due to a %ad
steric interaction' Which o the ollo!in" dia"rams illustrates this#
Feedback: In dia"ram A$ the methyl "roup is too close to the side chain' In the other dia"rams$ there is &ery
little steric interaction since one o the "roups in&ol&ed is a small hydro"en'
Page reference: )4)+)4:
,a' >ia"ram A
%' >ia"ram 0
c' >ia"ram C
d' >ia"ram >
)2) /he ollo!in" dia"ram sho!s the synthetic route to omepra1ole' What !ere the unctional "roups L and
M#
Feedback: /he thiol "roup is con&erted to a thiolate ion in the presence o sodium hydro3ide and acts as a
nucleophile to displace a chloride ion rom the alkyl chloride'
Page reference: )90
a' L28.$ M2Cl
,%' L2Cl$ M28.
c' L28Cl$ M2Ci
d' L2Ci$ M28Cl
)3) /he ollo!in" dia"ram sho!s &arious conormations or the cyano"uanidine "roup o cimetidine' A study
!as carried out to ind out the most sta%le conormations'
Which o the ollo!in" statements is true#
Feedback: /he study sho!ed that the =N and N= tautomers !ere a&oured and that the NN and ==
tautomers !ere not' /his demonstrated that t!o hydro"en %ondin" interactions !ere takin" place to t!o
dierent hydro"en %ondin" "roups in the %indin" site$ thus dispro&in" the chelation %ondin" theory'
Page reference: )4)+)4:
a' /he study sho!ed that only the Z,E tautomer is a&oured'
%' /he study esta%lished that there is only one hydro"en %ondin" interaction %et!een the "uanidine unit and
the %indin" re"ion'
c' /he study sho!ed that only the E,Z tautomer is a&oured'
,d' /he study dispro&ed the chelation theory o hydro"en %ondin"'
Title: Chapter 22 J Question )*
)*) /he ollo!in" dia"ram sho!s a parietal cell releasin" .Cl into the stomach' Identiy A+>'
Feedback: /he proton pump is responsi%le or pumpin" protons out o the parietal cell and potassium ions
into the parietal cell' Acetylcholine is a neurotransmitter that interacts !ith choliner"ic receptors on parietal
cells to increase the release o hydrochloric acid into the stomach' /he hormone "astrin and the local
hormone histamine ha&e the same eect !hen they interact !ith their correspondin" receptors'
Page reference: ))*+))4
a' -astrin 2 >
%' .istamine 2 0
c' Proton pump 2 A
d' Acetylcholine 2 C
)4) /he ollo!in" dia"ram illustrates a parietal cell' What is the eature la%elled A#
Feedback: Aeature A is the proton pump responsi%le or pumpin" protons into the lumen o the stomach'
Potassium ions are %rou"ht into the parietal cell in e3chan"e and the process is po!ered %y the hydrolysis
o A/P'
a' /he histamine receptor
%' Adenylate cyclase
c' An ion channel or chloride ions
,d' /he proton pump
Title: Chapter 22 + Question ))
))) /he ollo!in" dia"ram illustrates a parietal cell !here eature A is the proton pump' What are the
species la%elled A+>#
o A/P' Chloride and potassium ions depart the parietal cells throu"h ion channels !hich are separate rom
the proton pump'
a' .ydrochloric acid 2 >
%' Chloride ions 2 C
c' Potassium ions 2 0
d' Protons 2 A
)9) /he ollo!in" dia"ram illustrates a parietal cell !here eature A is the proton pump' What is the space
indicated %y the la%el =#
o A/P' Chloride and potassium ions depart the parietal cells throu"h ion channels !hich are separate rom
the proton pump' /he canaliculus is the channel into !hich these ions enter and lea&e' .Cl is released rom
the canaliculus into the stomach lumen'
a' 8tomach lumen
%' Parietal channel
,c' Canaliculus
d' Parietal outlet
Title: Chapter 22 + Question ):
):) /he ollo!in" structure is the proton pump inhi%itor omepra1ole
6mepra1ole under"oes a series o arran"ements in the acid conditions o the canaliculus %eore reactin"
!ith cysteine residues o the the proton pump' Which o the ollo!in" structures is the structure responsi%le
or that alkyation#
Feedback: /he thiol "roup o cysteine acts as a nucleophile and reacts !ith structure A to produce a
disulide co&alent %ond %et!een the amino acid and the dru"' /he other structures sho!n are ormed in the
mechanism %y !hich omepra1ole is con&erted to structure A'
Page reference: )))+))9
,a' 8tructure A
%' 8tructure 0
c' 8tructure C
d' 8tructure >
Title: Chapter 22 + Question );
);) /he ollo!in" mechanism sho!s ho! proton pump inhi%itors are acti&ated' Which arro! is incorrect#
Feedback: Arro! 0 is pointin" the !ron" !ay' Curly arro!s represent the mo&ement o electrons' A proton
has no electrons and so it ne&er makes sense to dra! an arro! rom a proton'
Page reference: )))+))9
a' A
,%' 0
c' C
d' >
90) Match the ollo!in" structures !ith the named dru"s:
Feedback: All the e3amples "i&en are proton pump inhi%itors'
Page reference: ))4
a' Fa%epra1ole 2 8tructure >
%' Cansopra1ole 2 8tructure C
c' 6mepra1ole 2 8tructure 0
d' Pantopra1ole 2 8tructure A
91) /he ollo!in" dia"ram sho!s some o the structures that !ere rele&ant to the de&elopment o an
important antiulcer dru"' Match the structures to the ollo!in" names:
Feedback: All the e3amples "i&en are proton pump inhi%itors'
Page reference: ))9+));
a' CM(131 2 8tructure 0
%' /imopra1ole 2 8tructure A
c' Picopra1ole 2 8tructure >
d' 6mepra1ole 2 8tructure C
important antiulcer dru"' Which o these structures !as the lead compound#
Feedback: 8tructure 0 is CM(131 !hich !as the lead compound$ %ut suered rom li&er to3icity'
a' 8tructure A
,%' 8tructure 0
c' 8tructure C
d' 8tructure >
important antiulcer dru"' In !hat order !ere they disco&ered#
Feedback: 8tructure 0 is CM(131 !hich !as the lead compound or the study' 8tructures A$ C and > are
timopra1ole$ omepra1ole and picopra1ole respecti&ely
a' A$ 0$ C$ >
,%' 0$ A$ >$ C
c' 0$ >$ A$ C
d' C$ >$ A$ 0
Title: Chapter 22 + Question 9*
9*) /he ollo!in" dia"ram sho!s some o the structures that !ere rele&ant to the de&elopment o an
important antiulcer dru"' Which o these structures !as disco&ered ollo!in" dru" meta%olism studies#
timopra1ole$ omepra1ole and picopra1ole respecti&ely'
>ru" meta%olism studies led to the reco"nition that the sulur atom in timopra1ole under!ent meta%olic
o3idation to produce an acti&e meta%olite'
,a' 8tructure A
%' 8tructure 0
c' 8tructure C
d' 8tructure >
important antiulcer dru"' Which o these structures !as ound to ha&e a side eect !hich in&ol&ed inhi%ition
o iodine uptake %y the thyroid "land#
timopra1ole$ omepra1ole and picopra1ole respecti&ely'
,a' 8tructure A
%' 8tructure 0
c' 8tructure C
d' 8tructure >
Title: Chapter 22 + Question 9)
9)) /he ollo!in" molecule is omepra1ole$ an important proton pump inhi%itor'
Which o the ollo!in" structures is a meta%olite#
Feedback: /he t!o maOor meta%olites o omepra1ole are sho!n %elo!'
Page reference: ));
,a' 8tructure A
%' 8tructure 0
c' 8tructure C
d' 8tructure >
99) /he ollo!in" molecule is omepra1ole$ an important proton pump inhi%itor'
Which o the ollo!in" structures is a meta%olite#
Feedback: /he t!o maOor meta%olites o omepra1ole are sho!n %elo!'
Page reference: ));
,a' 8tructure A
%' 8tructure 0
c' 8tructure C
d' 8tructure >

Patrick TB Ch22

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Patrick: An Introduction to Medicinal Chemistry 3e

Chapter 22: Antiulcer agents

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