Patrick Tb Ch22

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Patrick: An Introduction to Medicinal Chemistry 3e

Chapter 22: Antiulcer agents

Type: multiple choice questionTitle:Chapter 22 Question 0101) 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 toinduce the release o "astric acid' (oradrenaline does not do this'Page reference:*2+*3a' Acetylcholine,%' (oradrenalinec' -astrind' .istamine

Type: matching questionTitle:Chapter 22 + Question 0202) /he structure o histamine is sho!n %elo!' What la%els are used to distin"uish the nitro"ens atpositions A$ 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 imidaole rin" closest to the side chain' /he nitro"en is the imidaole nitro"en urthesta!ay rom the side chain'Page reference:**

a' A

%'

c' C

Type: multiple choice questionTitle:Chapter 22 Question 0303) What sort o heterocyclic rin" is present in histamine#Feedback:/he rin" systems "i&en are as ollo!s

Page reference:**a' Imidaolidine%' Pyridine

c' Pyrrole,d' Imidaole

Type: multiple choice questionTitle: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 noteist' /he .1 receptor is tar"eted %y traditional antihistamines !hile the .2 receptor is tar"eted %yhistamine anta"onists used in anti+ulcer therapy'Page reference:**+*4,a' .1%' .2c' .3

d' .*

Type: multiple choice question

OXFORDH i g h e r E d u c a t i o n5 6ord 7ni&ersity Press$ 200' All ri"hts reser&ed'


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Title:Chapter 22 Question 0404) 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'Page reference:**+*4a' .ay e&er%' Insect %ites

,c' 7lcersd' Asthma

Type: multiple choice questionTitle:Chapter 22 Question 00) /here are t!o possi%le tautomers or histamine'

/automer A is more sta%le than tautomer ' 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'

Type: multiple choice questionTitle:Chapter 22 Question 0909) /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 * othe 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 eperiences this inducti&e eect to a "reater

etent' /his makes the nitro"en more %asic and more likely to use its lone pair o electrons to %ond to

hydro"en'Page reference:43a' /he relati&e population o !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'



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Type: multiple choice questionTitle:Chapter 22 Question 00) /here are t!o possi%le tautomers or histamine' A methyl "roup at position * plays an important rolein 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 ascimetidine'Page reference:43a' 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'

Type: multiple choice questionTitle: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 secretionc' It has no eectd' It completely s!itches o secretion


Title:Chapter 22 Question 1010) 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 acidsecretion !ould decrease' It !ould not %e stopped completely since "astric acid and acetylcholine arestill a%le to stimulate "astric acid secretion'Page reference:*3+**a' It !ould increase secretion,%' It !ould decrease secretionc' It !ould ha&e no eectd' It !ould stop secretion completely

Type: multiple choice questionTitle:Chapter 22 + Question 11

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'Page reference:*+*



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,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'Page reference:*+*d' /he structure %inds to the receptor$ pre&ents the natural messen"er rom %indin" and eliminates anyinherent 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'Page reference:*+*

Type: multiple choice questionTitle:Chapter 22 Question 12

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


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Feedback:/he %indin" theory !as called the chelation %indin" theory and in&ol&es the "uanidine andcar%oylate ion interactin" throu"h ionic and hydro"en %ondin" interactions'Page reference:*+*;a' Ionic %indin" theory%' .ydro"en %ondin" theory,c' Chelation %indin" theoryd' Compleation %indin" theory


Title:Chapter 22 Question 1414) /he ollo!in" structures sho! some o the important molecules leadin" to the disco&ery o structure'

What sort o unctional "roup has %een introduced in 8?@ ;141#Feedback:/he unctional "roups descri%ed in the options are as sho!n %elo!:

Page reference:40+41

a' -uanidine%' 7rea,c' /hiouread' /hioamide

Type: multiple choice questionTitle:Chapter 22 Question 11) /he ollo!in" structures sho! some o the important molecules leadin" to the disco&ery o structure'



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A unctional "roup has %een introduced in 8?@ ;141' What !as the rationale or introducin" thisunctional "roup#Feedback:8tructure is %urimamide' /he rationale !as to replace the %asic "uanyl "roup !ith aneutral "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 sie and shape'Page reference:40+41

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 sie o the terminal unctional "roup'

Type: multiple choice questionTitle:Chapter 22 Question 1919) /he ollo!in" structures sho! some o the important molecules leadin" to the disco&ery o structure'

What !as the rationale or the strate"y used in de&elopin" structure rom 8?@ ;141#Feedback:8tructure is %urimamide' /he anta"onist %indin" re"ion is urther a!ay rom the imidaole%indin" re"ion than the a"onist %indin" re"ion' /hereore$ etendin" the distance %et!een the thiourea

"roup and the imidaole rin" increases the chances that the molecule !ill %ind as an anta"onist ratherthan an a"onist'Page reference:41a' /o reduce the inducti&e eect o the terminal unctional "roup on the imidaole rin"'%' /o increase the lei%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 theanta"onist %indin" re"ion',d' /o mo&e the terminal unctional "roup closer to the anta"onist %indin" re"ion and a!ay rom thea"onist %indin" re"ion'

Type: multiple choice questionTitle:Chapter 22 Question 11) /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#



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Feedback:8ince the electron !ithdra!in" eect o the cyanide "roup is inducti&e$ it is eperiencedmost %y the nitro"en directly attached to cyanide' As a result$ this nitro"en !ill %e the least %asic o thethree nitro"ens present in the "uanidine moiety and the least likely to %ond to hydro"en'Page reference:4a' /automer I,%' /automer IIc' /automer IIId' /hey are all eBual in sta%ility

Type: matching questionTitle:Chapter 22 + Question 1;

1;) /he ollo!in" synthetic route has %een used to produce cimetidine'

What rea"ents !ere used in steps A$ and C#Feedback:ithium aluminium hydride is a po!erul reducin" a"ent capa%le o reducin" car%onyl "roupssuch 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"onucleophilic su%stitution !ith 2+aminoethanethiol'Methylamine in ethanol is used to su%stitute the methylthio "roup in the penultimate structure !ith amethylamino "roup'Page reference:49a' 8tep A ithium aluminium hydride%' 8tep *D hydro"en %romide and 2+aminoethanethiol

c' 8tep C Methylamine in ethanol

Type: multiple choice questionTitle:Chapter 22 Question 2020) /he ollo!in" "raph measures lo"


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What is measured %y lo" P#Feedback:o" Pmeasures the o&erall hydropho%icity o a molecule'Page reference:4+4;a' 8ie,%' .ydropho%icityc' asicityd' >ipole moment



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Feedback:/he lo" P&alue or this "roup is relati&ely lo! and the compound should ha&e a lo!eracti&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 sie 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'

Type: multiple choice questionTitle:Chapter 22 Question 2*2*) /he ollo!in" "raph measures lo"


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/he nitroketeneaminal "roup does not it the line o the "raph' /his "roup is present in a clinicallyimportant anti+ulcer dru"' Identiy the dru"'Feedback:Fanitidine has the ollo!in" structure

Page reference:2,a' Fanitidine%' amotidine

c' amitidined' otidine

Type: multiple choice questionTitle:Chapter 22 Question 22) A Q8AF study o cimetidine analo"ues !ith dierent planar "roups produced the ollo!in" eBuationG

lo"


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Page reference:0+1

,a' 0o

%' *4o

c' 0o

d' ;0o

Type: multiple choice questionTitle:Chapter 22 Question 22) What enyme catalyses the ollo!in" reaction#

Feedback:Car%onic anhydrase catalyses the ormation o car%onic acid rom !ater and car%on dioide'/he acid dissociates to "i&e a proton and a hydro"en car%onate ion'Page reference:4a' Car%onic synthase%' Car%onic li"ase,c' Car%onic anhydrase

d' Car%onic hydrolase

Type: multiple choice questionTitle:Chapter 22 Question 2;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 thetriphosphate 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 AMPc' A/P to cyclic AMPd' A/P to adenosine

Type: multiple choice questionTitle:Chapter 22 Question 3030) /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 thecanaliculae o parietal cells'Page reference:a' In the li&er%' In the %lood supplyc' In parietal cells,d' In the canaliculae o parietal cells

Type: multiple choice questionTitle:Chapter 22 Question 31

31) What is the typical pKaor proton pump inhi%itors#Feedback:/he proton pump inhi%itors are !eak %ases and reBuire stron" acidic conditions %eore theyprotonate and %ecome acti&ated'Page reference:,a' *%' c' 9'*d' ;

Type: multiple choice questionTitle:Chapter 22 Question 3232) 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 theyprotonate and %ecome acti&ated'Page reference:



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,a' 8tron"ly acidic conditions%' Weakly acidic conditionsc' (eutral conditionsd' 8li"htly %asic conditions


Title:Chapter 22 Question 3333) /he ollo!in" dia"ram sho!s the de&elopment o the irst commercially a&aila%le proton pumpinhi%itor omepraole


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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 eposed re"ions o the pyridine rin"'d' /hey %lock the dru" %indin" to alternati&e tar"ets'

Type: multiple choice questionTitle:Chapter 22 Question 3434) /he ollo!in" dia"ram sho!s the de&elopment o the irst commercially a&aila%le proton pumpinhi%itor omepraole


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the su%stituent is at the metaposition$ this resonance structure is no lon"er possi%le' /his means thatthe 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

Type: multiple choice questionTitle:Chapter 22 Question 33) /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 omepraole and this !as !hat led to thestructure %ein" called esomepraole'Page reference:;a' =spantopraole%' =slansopraole,c' =somepraoled' =sra%epraole

Type: multiple choice questionTitle:Chapter 22 Question 3939) /he ollo!in" structure


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What !ere the rea"ents used or step A and step

Feedback:8odium hydroide con&erts the thiol to a thiolate !hich can then displace the chloride romthe alkyl chloride &ia a nucleophilic su%stitution reaction' /he meta+chloroper%enoic acid is an oidisin"a"ent !hich is oten used as an epoidisin" a"ent$ %ut !hich in this case is used to oidise the sulphuratom o the penultimate compound'Page reference:90a' 8tep A 8odium hydroide%' 8tep Meta+chloroper%enoic acid

Type: multiple choice questionTitle:Chapter 22 Question 3;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 intothe 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:92a' 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"entsd' /!o proton pump inhi%itors and an anti%acterial a"ent

Type: multiple choice questionTitle: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'Page reference:**+*4,a' 8tructure A%' 8tructure c' 8tructure Cd' 8tructure >


Title:Chapter 22 + Question *1



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*1) Which nitro"en atom


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Feedback:8tructure C is %urimamide' 8tructure is N +"uanylhistamine' 8tructures A and > arecompounds that !ere de&eloped rom N +"uanylhistamine and !hich led to the disco&ery o %urimamide'Page reference:*+4*a' A$ $ >$ C%' $ A$ C$ >,c' $ A$ >$ C

d' $ >$ A$ C

Type: multiple choice questionTitle: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 is N +"uanylhistamine' 8tructures A and > arecompounds that !ere de&eloped rom N +"uanylhistamine and !hich led to the disco&ery o %urimamide'Page reference:*+4*a' 8tructure A%' 8tructure ,c' 8tructure Cd' 8tructure >

Type: multiple choice questionTitle:Chapter 22 + Question *4*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#



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Feedback:8tructure 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

Page reference:*+4*a' 8tructure A,%' 8tructure c' 8tructure C

d' 8tructure >

Type: multiple choice questionTitle: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 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'

Page reference:*+4*a' 8tructure !as de&eloped rom structure A usin" a chain etension 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 etension strate"y',d' 8tructure C !as de&eloped rom structure > usin" a chain etension strate"y'

Type: multiple choice questionTitle:Chapter 22 + Question *9*9) /he ollo!in" structures sho! some o the important molecules leadin" to the disco&ery o structure '

Which o the ollo!in" statements concernin" structure is untrue#



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Feedback:It esta%lished that %indin" to the anta"onist %indin" re"ion in&ol&ed hydro"en %ondin" and notionic %ondin"'Page reference:40+41a' It esta%lished the eistence 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"'

Type: matching questionTitle:Chapter 22 + Question **) Identiy the ollo!in" structures

Feedback:urimamide !as the irst o the our compounds named to %e de&eloped and esta%lished theeistence o .2 receptors' /hia%urimamide !as de&eloped %y introducin" a sulphur atom into the side chaino %urimamide' Metiamide in&ol&ed the urther addition o a methyl su%stituent to the imidaole rin" andcimetidine in&ol&ed replacement o the thiourea "roup !ith cyano"uanidine "roup'

Page reference:40+44a' Cimetidine 8tructure %' /hia%urimamide 8tructure Cc' Metiamide 8tructure >d' urimamide 8tructure A

Type: multiple choice questionTitle:Chapter 22 J Question *;*;) Which o the ollo!in" structures has an electron donatin" side chain attached to the imidaole rin"#

Feedback:/he structures sho!n ) are %urimamide$ cimetidine$ thia%urimamide and metiamide

respecti&ely' urimamide has an electron donatin" side chain' /he other structures contain sulur in the sidechain$ makin" the su%stituent electron !ithdra!in"'Page reference:40+44



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,a' 8tructure A%' 8tructure c' 8tructure Cd' 8tructure >


Title:Chapter 22 J Question 4040) /he ollo!in" structures !ere part o a study aimed at indin" anti+ulcer a"ents' What sort o mode oaction do they ha&e#

Feedback:/he structures sho!n ) are %urimamide$ cimetidine$ thia%urimamide and metiamiderespecti&ely' /hey all act as anta"onists at the .2 receptor'Page reference:40+44a' /hey are receptor a"onists,%' /hey are receptor anta"onistsc' /hey are enyme inhi%itorsd' /hey %lock carrier proteins

Type: multiple choice questionTitle:Chapter 22 J Question 4141) /he ollo!in" structures !ere part o a study aimed at indin" anti+ulcer a"ents' What is their tar"et#

Feedback:/he structures sho!n ) are %urimamide$ cimetidine$ thia%urimamide and metiamiderespecti&ely' /hey all act as anta"onists at the .2 receptor'Page reference:40+44a' /he proton pump%' /he .1 receptor,c' /he .2 receptor

d' /he "astrin receptor



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Type: multiple choice questionTitle:Chapter 22 + Question 4242) /he ollo!in" structures !ere part o a study aimed at indin" anti+ulcer a"ents' Which o the structureshas the p?aor the imidaole rin"#

Feedback:/he structures sho!n ) are %urimamide$ cimetidine$ thia%urimamide and metiamiderespecti&ely' urimamide has an electron donatin" side chain "i&in" it a p?a o 9'24' /he other structurescontain 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" inluenceo the side chain "i&in" it a p?a o '0' or the same reson$ the p?a or the imidaole rin" o cimetidine isalso hi"her than the p?a or thia%urimamidePage reference:40+44a' 8tructure A%' 8tructure ,c' 8tructure Cd' 8tructure >

Type: multiple choice questionTitle:Chapter 22 + Question 4343) /he ollo!in" structures !ere part o a study aimed at indin" anti+ulcer a"ents' In !hat order !ere thestructures de&eloped#

Feedback:/he structures sho!n ) are %urimamide$ cimetidine$ thia%urimamide and metiamiderespecti&ely'Page reference:40+44a' C$ A$ $ >%' $ >$ C' A

,c' A$ C$ >$ d' >$ $ C$ A



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Type: multiple choice questionTitle:Chapter 22 + Question 4*4*) /he ollo!in" structure is cimetidine' Which electron donatin" "roup is present to a&our the acti&etautomeric orm o the imidaole rin" sho!n#

Feedback:/he methyl "roup has an inducti&e electron donatin" eect on the imidaole 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'Page reference:41+44

,a' -roup a%' -roup %c' -roup cd' -roup d

Type: multiple choice questionTitle:Chapter 22 + Question 4444) /he ollo!in" structure is cimetidine' Which electron !ithdra!in" "roup is present to a&our the acti&etautomeric orm o the imidaole rin" sho!n#

Feedback:/he sulur has an inducti&e electron !ithdra!in" eect on the imidaole 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'Page reference:41+44a' -roup a,%' -roup %

c' -roup cd' -roup d

Type: multiple choice questionTitle:Chapter 22 + Question 44) /he ollo!in" structure is cimetidine' Which "roup is present to interact !ith a hydro"en %ondin" re"ionnot used %y histamine#



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Feedback:-roup d is a naturally occurrin" moiety !hich is neutral and interacts !ith a %indin" re"ionthrou"h hydro"en %ondin"' It !as used to replace a thiourea "roup in pre&ious structures since the latter!as responsi%le or toic side eects'Page reference:41+44a' -roup a%' -roup %

c' -roup c,d' -roup d

Type: multiple choice questionTitle:Chapter 22 + Question 4949) /he ollo!in" structure is cimetidine' /he "uanidine moiety at the end o the side chain is neutral !hichis unusual since "uanidine moieties are usually %asic' Which one o the coloured "roups sho!n isresponsi%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

Type: multiple choice questionTitle:Chapter 22 + Question 44) Which o the ollo!in" structures is a meta%olite o cimetidine#

Feedback:/he meta%olites o cimetidine are sho!n %elo!'



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Page reference:4,a' 8tructure A%' 8tructure c' 8tructure Cd' 8tructure >

Type: multiple choice questionTitle: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:4a' 8tructure A%' 8tructure c' 8tructure C,d' 8tructure >

Type: matching questionTitle:Chapter 22 + Question 00) /he synthetic route to cimetidine is sho!n %elo!:



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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 sidechain on a startin" material already containin" the reBuired imidaole rin"'Page reference:49a' A 8tructure III%' 8tructure IIc' C 8tructure Id' > 8tructure IK

Type: multiple choice questionTitle:Chapter 22 + Question 11) /he ollo!in" conormation or the cyano"uanidine "roup o cimetidine is not a&oured due to a %adsteric 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 &erylittle steric interaction since one o the "roups in&ol&ed is a small hydro"en'



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Page reference:4+4,a' >ia"ram A%' >ia"ram c' >ia"ram Cd' >ia"ram >

Type: multiple choice questionTitle:Chapter 22 + Question 22) /he ollo!in" dia"ram sho!s the synthetic route to omepraole' What !ere the unctional "roups L and#

Feedback:/he thiol "roup is con&erted to a thiolate ion in the presence o sodium hydroide and acts as anucleophile to displace a chloride ion rom the alkyl chloride'Page reference:90a' L8.$ Cl

,%' LCl$ 8.c' L8Cl$ id' Li$ 8Cl

Type: multiple choice questionTitle:Chapter 22 + Question 33) /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!odierent hydro"en %ondin" "roups in the %indin" site$ thus dispro&in" the chelation %ondin" theory'Page reference:4+4a' /he study sho!ed that only the Z,Etautomer is a&oured'%' /he study esta%lished that there is only one hydro"en %ondin" interaction %et!een the "uanidine unit andthe %indin" re"ion'c' /he study sho!ed that only the E,Ztautomer is a&oured'

,d' /he study dispro&ed the chelation theory o hydro"en %ondin"'

Type: matching question



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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 ionsinto the parietal cell' Acetylcholine is a neurotransmitter that interacts !ith choliner"ic receptors on parietalcells to increase the release o hydrochloric acid into the stomach' /he hormone "astrin and the localhormone histamine ha&e the same eect !hen they interact !ith their correspondin" receptors'Page reference:*+4a' -astrin >%' .istamine c' Proton pump Ad' Acetylcholine C

Type: multiple choice questionTitle:Chapter 22 + Question 44) /he ollo!in" dia"ram illustrates a parietal cell' What is the eature la%elled #



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Feedback:eature 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 echan"e and the process is po!ered %y the hydrolysiso A/P'Page reference:*+4a' /he histamine receptor%' Adenylate cyclasec' An ion channel or chloride ions,d' /he proton pump

Type: matching questionTitle:Chapter 22 + Question ) /he ollo!in" dia"ram illustrates a parietal cell !here eature is the proton pump' What are thespecies la%elled A+>#

Feedback:eature 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 echan"e and the process is po!ered %y the hydrolysiso A/P' Chloride and potassium ions depart the parietal cells throu"h ion channels !hich are separate romthe proton pump'

Page reference:*+4a' .ydrochloric acid >%' Chloride ions C



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c' Potassium ions d' Protons A

Type: multiple choice questionTitle:Chapter 22 + Question 99) /he ollo!in" dia"ram illustrates a parietal cell !here eature is the proton pump' What is the space

indicated %y the la%el =#

Feedback:eature 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 echan"e and the process is po!ered %y the hydrolysiso 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 romthe canaliculus into the stomach lumen'Page reference:*+4a' 8tomach lumen%' Parietal channel,c' Canaliculusd' Parietal outlet

Type: multiple choice questionTitle:Chapter 22 + Question ) /he ollo!in" structure is the proton pump inhi%itor omepraole

6mepraole 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#



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Feedback:/he thiol "roup o cysteine acts as a nucleophile and reacts !ith structure A to produce adisulide co&alent %ond %et!een the amino acid and the dru"' /he other structures sho!n are ormed in themechanism %y !hich omepraole is con&erted to structure A'Page reference:+9,a' 8tructure A%' 8tructure c' 8tructure Cd' 8tructure >

Type: multiple choice questionTitle:Chapter 22 + Question ;;) /he ollo!in" mechanism sho!s ho! proton pump inhi%itors are acti&ated' Which arro! is incorrect#

Feedback:Arro! is pointin" the !ron" !ay' Curly arro!s represent the mo&ement o electrons' A protonhas no electrons and so it ne&er makes sense to dra! an arro! rom a proton'Page reference:+9a' A,%' c' Cd' >

Type: matching questionTitle:Chapter 22 + Question 9090) Match the ollo!in" structures !ith the named dru"s:



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Feedback:All the eamples "i&en are proton pump inhi%itors'Page reference:4a' Fa%epraole 8tructure >%' ansopraole 8tructure Cc' 6mepraole 8tructure d' Pantopraole 8tructure A

Type: matching questionTitle:Chapter 22 Question 9191) /he ollo!in" dia"ram sho!s some o the structures that !ere rele&ant to the de&elopment o animportant antiulcer dru"' Match the structures to the ollo!in" names:

Feedback:All the eamples "i&en are proton pump inhi%itors'Page reference:9+;a' CM(131 8tructure %' /imopraole 8tructure Ac' Picopraole 8tructure >d' 6mepraole 8tructure C

Type: multiple choice questionTitle:Chapter 22 + Question 9292) /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 the lead compound#



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Feedback:8tructure is CM(131 !hich !as the lead compound$ %ut suered rom li&er toicity'Page reference:9+;a' 8tructure A,%' 8tructure c' 8tructure C

d' 8tructure >

Type: multiple choice questionTitle:Chapter 22 J Question 9393) /he ollo!in" dia"ram sho!s some o the structures that !ere rele&ant to the de&elopment o animportant antiulcer dru"' In !hat order !ere they disco&ered#

Feedback:8tructure is CM(131 !hich !as the lead compound or the study' 8tructures A$ C and > aretimopraole$ omepraole and picopraole respecti&elyPage reference:9+;a' A$ $ C$ >,%' $ A$ >$ C

c' $ >$ A$ Cd' C$ >$ A$

Type: multiple choice questionTitle: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 animportant antiulcer dru"' Which o these structures !as disco&ered ollo!in" dru" meta%olism studies#



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Feedback:8tructure is CM(131 !hich !as the lead compound or the study' 8tructures A$ C and > aretimopraole$ omepraole and picopraole respecti&ely'>ru" meta%olism studies led to the reco"nition that the sulur atom in timopraole under!ent meta%olicoidation to produce an acti&e meta%olite'

Page reference:9+;,a' 8tructure A%' 8tructure c' 8tructure Cd' 8tructure >

Type: multiple choice questionTitle:Chapter 22 + Question 9494) /he ollo!in" dia"ram sho!s some o the structures that !ere rele&ant to the de&elopment o animportant antiulcer dru"' Which o these structures !as ound to ha&e a side eect !hich in&ol&ed inhi%itiono iodine uptake %y the thyroid "land#

Feedback:8tructure is CM(131 !hich !as the lead compound or the study' 8tructures A$ C and > aretimopraole$ omepraole and picopraole respecti&ely'Page reference:9+;,a' 8tructure A%' 8tructure c' 8tructure Cd' 8tructure >

Type: multiple choice questionTitle:Chapter 22 + Question 99) /he ollo!in" molecule is omepraole$ an important proton pump inhi%itor'



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Which o the ollo!in" structures is a meta%olite#

Feedback:/he t!o maOor meta%olites o omepraole are sho!n %elo!'

Page reference:;,a' 8tructure A%' 8tructure c' 8tructure Cd' 8tructure >


Title:Chapter 22 + Question 9999) /he ollo!in" molecule is omepraole$ an important proton pump inhi%itor'

Which o the ollo!in" structures is a meta%olite#



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Feedback:/he t!o maOor meta%olites o omepraole are sho!n %elo!'

Page reference:;,a' 8tructure A%' 8tructure c' 8tructure Cd' 8tructure >


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