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Med Chem Exam 1_1998

Med Chem Exam 1_1998 - Medicinal Chemistry 311 Name October...

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Unformatted text preview: Medicinal Chemistry 311 Name October El. 1993 Student Nd- Examination #1 Use your adigfi person number. leave are Est {Stilt} space blank. For the multiple choice questions. select the one best answer. [2 points each} If you change an answer. be certain to erase the original bubble corrqiletely. it is your responsibility.r to answer the quesdsrs on the to pages of the examination. 1. Medicinal Chemistry. Biochemical Pia-macalogy and Pharmaceutics are disciplines in their own right and they Lnderpin professional Pham'racy cun'iculums. However. medicinal mm a] design a. make drug dosage films. e.g. tablets and rapsules. @dlscover. design 8. synthesize rtugs. c) make dnJg targets. d} primarily study the effects of drugs in the body. e] b s c Historical. For questions 2 and 3. select the appropriate person and enter the appropriate letter on the bubble sheet: a} Sheri Ming- bl Frederich Serturner. cl John Abel. cl} Paul Ehrlich. a] William Witherlng b 2. When chemistry was done primarilyr :1.- phan'nacisls. this pharmacist was the first person to isolate a pure alkaloid drcg from plants. {3 £3” 3. This scholar compiled a book of herbs it which he described plants that contained the alkaloids ephedrine and mine for use as dogs CL! About Sources of Dmgs. 4. Examples of classes of dnrgs obta‘nec from plants are d a] alkaloids. a.g. reserpine and "codeine. b} purines. e.g. iheophyiiine arc caffeine. c captopril and phenobarbital. 3: b. e} a. b. 3: c. 5. Compared to the solubilityr of alkaloids in water. the solubility of alkaloid salts. e.g- sulfates. hydrochlorides and nitraas. is b a] less than alkaloids. .reater than alkaloids. c} the same as alkaloids. became alkaloids do not form salts with acids. ID: 1". I 6. A common so'uccuiat feature of all alkaloids is the ammlm i“ f- .C 111': l - t“? b} amide gm Jfl J __ til -J 6‘ a} aster gm L'Lif‘LU L Q @amine group a} aminal add group I 7. Drugs from plants mayr be discovered through a] scieening lam-arse made from plants. I (fix in} infinity rec-ms. c} ethnopharmacologyfloildore. l 8. When screening a targe number of plants for potential drugs, scientists matte plant extracts. purify them, and obtain pure drugs. Next, the pure dmgs are 1‘ tested for the desired biological activity using an appropriate screen- 9. Dmgs that can be obtained from animals include a} morphine-4;: to) insulin a Ch. I '. e, c} heroin 4;: - dsteroidsrfl (grad ‘ 1t}. ‘i’u'hich of the following structures is characteristic of steroids? . O Fl: H Cl s ' W Mire“ :fl I pm at t m tdk ‘ 11. Insulin is an mie of a an alkaloid no I ( :5 PDIB'PEPfifl-E b c] a steroid . cl} an aminogiycoside I e} a fat-sohtie 1ritsrnin an 3/ 12. Tee antibiotic penjcilfins and tetracycline are concomitant obtained from ff» / a} tire chemist's laboratory by organic synthesis. 0 b) higher plants. .._ ~ 0U}; i . '7 & c bacteria via recombiant DNA technologyrefii {ELM} P” E Cl . ngi. molds e) c 8. d 13. Application of recombinant DNA tachnology leads to a ciass of compounds called @enpepfieee cyciopantanyipernydrophenanthrenes c} polysaccharides d} prostagiandins e} polygiutamates 14. in recombinant DNA technology bacterial a} RNA is modified. 5 C/ b} mitochondrial DNA is modified. "'- @plesmid one is modified. d) nuclear DNA is modified. " e} chromosomal DNA is modified. ‘ About Drug Diemvery. 15. Tee alkaloid cocaine. a usefui local anesthetic used in eye surgery. can cause d'remitai dependency (addiction) if improperly used. The structure of cocaine was used to develop a series of new sbucturally—reiated. non—addicting locsi aesthetics. including procaine (Nova-aim. In terms of new drug development. cocaine was used as a} a primary standard. \0 CED lead compound. c} a starting material for synthesis of procaine. d‘} a 8. in sees 16. Vii-an designing and making drugs to treat diseases. chemists are aided by a lmowiedge of physiology, biochemistry. etc. ofthe diseases in question. That know-edge is irnrnediatety {next} used by chemists to a) test for drug activity «@denfify drug targets. b ‘Ej'synthesize defiva'tives of dmgs. d) predict the toxicities of drugs. _ e} predict SARs. , About lsosten'sm. 1?. Select an isostatic replacement for the alcohol group of glycopvrrolate. an antichotinergic drug. P C 1‘ H I h Du Eat-i NH” O: éoé”: Us”)? bi \ 13. When making an optimum new drug. medicinal chemists wiil make manv derivatives ofihe prototvpe drug. Each drug wiil be more, or less active-than the previoust made drugs in the series. This leads to a group of SARs, which are used by medicinal chemists to a} -O- b] -CH= c} -NH- @5“ a} =N= + a) predict which substituents will lead to more active dmgs. b} define isosteric atoms and groups of atoms. _ c) change the prototype athletes to obtain the optimum or “best' dmg. d afib on: g'flfihfl/k I, About Drug Absorption and Storage. QT“ ’ . 19. Dmgs in die blood stream are gmfiefiound to some extent to serum proteins. eg. serum albumin. For drug , Kn = 3 x 10‘" M: for drug E. KD= 2 x 1D lvl, where K, is the [dung-serum albumin complex} dissociation constant a} Serum protein-bound drugs are active at receptors. b} Dmg B binds more strongly iao serum albumin than does dnJg A. @mgs A E. B can dissociate from complexes and be available to react with receptors. :1) a 3. b d] a 3: c N’ i 2B. When partitioned between a mixture of the iipopnflic solvent octanol and water. drug A's solubility is 3 mgitfl mL in octanol and 4 mgitflfl mL in water. Thevalue ofP fordmgAip. , . . ‘~.; ._ Ce. ' a) L15 .ili £11 3‘ ’r b}: . _ 33’;- E— - 1:} 32 _,:J'('____. " f 91‘; a (it . .33 {i Ztifleqr—otitg'factorsbeingaqualdhedmgabsorbed metastesthastheF 'airm 4‘ P tale” e} None of the above because dmg absorption is not dependent on the value of F. AboutR 21 Some membrane-associated receptors a] have enzyme activity [e.g., tvrosine kinase activity). . b] control passage of water-soluble ions across lipid-like cell membranes. c} are coupled to 'G' proteins. 21Mernbrane~associated receptors are essentially:r polvsacd1afides.and theyIr provide a mechanism for cells to communicate information to other cells. aTRUE ALSE 24. Activation of G—protein {of G-protein-ooupled receptors} involves replacement of guanosine diphosphate {GDP} which' a bound to resting' G protein by guanosine triphosphate {GTP}. @reu-s. b) FALSE 25 An intracellular second messenger synthesized when G protein-coupled receptors are activated Is 3' 5‘ -cyctic adenosine monepnospnate (CAMP). ..I'. J'- Q'NJE -} QIFA LEE '1‘ About Bonding of Drugs and Receptors. 25. Drugs Ell-X bind to enzyme E—Y. and inhibit it. D-Xs and KD values are: D—COE'. L113 :11“: D-CgHu. 513D nM; D-GHZDH, 10 nM: D—NH; . 1o.ooo nM. The most likely bond formed between groups I and Y of drug and enzyme is a] an ionic bond with Y = C021 b) a hydrogen bond wilh Y = CH3. c) a hydrophobic bond. d] an ion-reinforced hydrogen bend with Y = CgHs {phenyl} . en ionic bond with y = NH; 2?. The majority of dmgs, especially phannacodynamic dmgs. generally fonn more than one reyersible, non-covalent bond with their targelsfreoeptorii“ ,FRUE . FALSE About Receptor Sbuctures. 23. In a site-specific labefing experiment. a worker reacted a selective alkyieting agent {A-CHECIJ wilt-i a receptor H. hydrolyzed the alkylated receptor A—R. isolated the amino acids and small pepfides ihat were aikylated, and identified the following 2 substances: senne{CHz-A} and HEN-histidine-serinemHrAHisddine-glycine-COOH. The primary amino acid sequence of the receptor [the order of the amino acids in the receptor) indicated the following amino acid sequences. among others: Hart—histidinell4)—alanine{15}-eerine{16)—hisfidtne{17]-CDOH HEN-alanine{93}-histidine{9?}—sedne{98)-hisfidme(99}-CODH HEN-lysineillBel-serineU95)—hisfidlne{196}-alanine{19?}-GDDH An amino acid in the receptor binding site is. a hisfidine{195} serine(95} c} histidine {97'} d) serinel15} e} serinef195} Ce/ (1.! 29. For reaction of a series of drugs with their reoeptcrto give a biologic response {BR} it can be shown that. Kg = constant [DRUG] and. log Kn = log constant + log [DRUG]. K9 is the dmg-receptor dissociation constant and {DRUG} fliedcseafeadidrugthalis regyiredtogivethestandard biological response- For several drugs that react with the sane receptor these equafions predict that slagraphafflogKDhahflsplofledagainst [log [DRUGDvaiuesofa seriesofdrttgswithlhesameithd ofaclivilyislinear. b} agraph ofKDvalues plotud against [DRUGiveluesofasefiesof drugswithlhestmeldndofadivityislinsar. c largevalueschaamassooiatedwidiniostacfivedmgs. &b e bac 3i]. sharpie-allyr of isolated membrane-associated receptors. the function {ion- gafing} of isolated cholinerglc receptors can be demonstrated by incorporating them into lipid vesicles merged with sodium ion. and measuring the release of sodiumion ficmdrevesicieswhen anacetvlchol‘me—flkedrugisaddedtolhe Booster—vesicle preparation- ut Metabolism. 31. Drug metabolism occurs in various organs of the body, but primarily in the liver. a UE FALSE 31 Drug metabofiles are usually more mdily exacted via the gastrointestinal tract and the kidneys than are their parent drugs because clmg metabolites generally.r have lower P values than the parent drug. UE ) FALSE ‘1’ 33. Phaaelmeiabciiam cfdrug Iii-CH; giveaanaicchciaacnecfthe metabolites. FhaseilnetabcfiemofmeaicohciwimUDP-ghncudcacidgiveaa giucurcnide. (3024-1 {D a}Thegiumniieialeaaacklhiehaquecuascluficmdmmeaimhei metabolite. h}Bofi1meflbcifleacanbeexpedfidtchemeadivefl=nd1eparafi_ drug. c} Thengnideiapmducadinmwreacticncfme meiwiu'l phmphnadmosimphospmcuflate. d} The giucm'enicacid partef the gflicumnfle has alcoheé radaidehyde groups. éNcneufflieabeve 3-4. Phase I metabolic cxidaiicn cf D—CH; can give a] Iii-CHO b] D—CHz-DH , c) D-GOzH {3" d h a. c x/ @c. b 8. c 35.ivietahmiamcffl1epmdmgcvmphcaphamidcin vivcultizmi'a-l giveaan active anticancer drug, phosphciamide m .The iniliai mega cx_idatic_n cf cvcicphcaphanlidg shown _b_eigj.v deg-LIE T .111“? rLumhered 1 E -. 5 21315.0 H}; ”HSP‘I m: “:1 _'i'r L Ricki-L. 4 ’ Narmada F” 1.1.91 Old” m.‘ H a] 1 d 5% e}5 9 $.Awnewdsaflmememsssmmmlysisnfestemsmdingtu megenemlschen'leshmn: ' til k2 E—ser—OH + Ester-m; E-ser-GHEstE—I-A + e_..c+ E-ssr-OH' ear-rims: 311(9) FarhydrolysisefthegenedeimesfluficEtnmflate. 0% D drewlhe mensesefkfl sndc ‘6sz mead a A=0H3fl41fl4> B= L...--' I V 0.. outflow/NC Had. b) {3) Exeieme, an aeetyi helium inhibitor, was mesnfly approved furthe heatnent of Alzheimer‘s disease. Exeienei. a poor substrate of seetyi chelinestersse, hm the stumrs: CH; i’ CH; UVN‘crh owe CH! Using the mechanism shown she-re draw the structure of inhibited seetyl choiinestersse (E-ser-DH}. E w???-sa—C-"mec‘ljF “~ch s) (3} ifExelantE-‘is asubstrateferfie enzyme. teiiwhyfl'leenzyme is inhflaited from hydmlyzing scetyl metineeamse The. aéarre clay! «ca-‘53»;- is HHW('§: 579119 New “EH-411mm :5 nor-ma! acwfiwng C cw; {Laria- ____fi____—-—————fi ..._————-”TT——— — ‘ ' Lutfi'mfimMflJ _. 4m _ 1U Draw the Wind mum. (Clea? dawn abbraviamd m an acceptable.) W a a) The 2 aaddafiva demelhylafim :rnducls. F3 3 fi‘ «35“? WE H/ R. H W‘LQW h}WpWWnpmdu: (x, :I‘ OH H 0'0“: c} The mega sky! afidafiun pm \_\'/ __.L £3 firm I' M? f a d} The pmducta of main-mud hydrulysis. ‘*- H 0H 5-H; *b-flfi rt“ " a7 a] The reducfion produn: fumed :1: reaction with an NADH—reqLfir'rng reductase. ...
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