Med Chem Exam 1 2000

Med Chem Exam 1 2000 - Medicinal Chemistry 311"...

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Unformatted text preview: Medicinal Chemistry 311" Name "fl m l . 3:.“ _ . - r - _ i October 5, zone . Student No. ' ' ' '. Examination #1 Use a No. 2 pencil. Write your name on the top of this exam and on the front and back of the bubble sheet. Use your B-digit person number {as ID No.) followed by a blank space [ch} on back of the bubble sheet. Fill in bubble sense where applicable. For the multiple choice questions, select the one best answer from one or more right answers {2 points each}. Write-in and short answer questions at the end are worth the points idicated. Read each question carefully. Double check all your answers; if you change an answer, be certain to erase the original answer completely. 1. Medicinal chemists a) discover. design a synthesize drugs b} design at make drug dosage forms. e.g. tablets c} primarily study the effects of drugs in the body 'd} are organic chemists by training are} a 8: d For questions 2 8: 3. select the appropriate person and enter the appropriate letter on the bubble sheet: a} John Abel. bi Gerhard Domagk. c) Paul Ehrlich. d} Alexander Fleming. e} William Withering. . 2. Nobel prize winning discoverer of a natural product. a prototype of a major drug up class. useful for treating bacterial infections. 3. Nobel prize winning discoverer of the antibacterial effect of a synthetic dye. This discovery marked the beginningpf the development of a major drug class and the acceptance of synthetic approaches to drug discovery and development. 4. The discipline of organic chemistry was born in 1328. when the vital force theory was overturned by Friedrich Wohler’s demonstration of the synthesis of the animal product urea {NH2ICDNH2} from the inorganic chemical: If. a} ammonium bicarbonate {NHdHCUs} i-I bi ammonium acetate {NHaDCUCHa} c} ammonium cyanate {NHaDCN} Nd} sodium acetate {NaUCUCHgi ‘ai sodium bicarbonate {NaHCDai 5. The solubility of alkaloids in water. compared to their hydrochloride salts is t 1* 'L a] greater . - -- -*-_’_Eijiless - c} the same .Ckiir'tl: it it '~ 6. Examples of classes of drugs that are made by plants are D {a} cardiac giycosides [steroidal sugars), e.g. digoxin b} polypeptides. like insulin {no .1i‘.‘fi=:'l.l 3‘ ictailreloidsr e.g. morphine said} a at c a} a. b. 3: c T. The most characteristic structural feature of alkal?ids is _ i; - (L‘s-1L“ '- , ,al'a neutral alcohol group . is“. __b}-an acidic carboxylic acid group ' c} a basic nitrogen ‘dLa neutral amide group finone ofthe aboye 8. Drugs of animal origin include lg) estrogena ; .J ._"|:_i}' insulin ci tetracycline. .32; d} a 3; b e} a, b a c 1-1 Q. The following structure represents I U h a} an alkaloid flit-53a steroid hormone of a peptide hormone d} a lipid soluble drug e} b a d 10. An example of an antibiotic {obtained from nature, by definition} is aTaspirin era; penicillin 'chi'reserpine dfcodeine .el sulfanilamide 11. Application of recombinant DNA technology leads to drugs that are difficult to synthesize and formulate. They mainly represent the following type of compounds: {as} amino acids d} oligonucleotides lb) proteins a} carbohydrates 'c'} steroids I.- II_;:\' ;'.I_!-;I.' -..F:;[’rlrl’zir 12. The majority of drugs used today were acquired by application of organic chemical synthesis. TRUE ' } FALsE 13. Codeine is an analgesic {pain reliever] and an antitussive {cough suppressant}. The development of dextromethcrphan as a nonprescription an antitussive was based on the structure of codeine. In terms ofthe synthesis and development of dextromethorphan as an antitussive. codeine served as DH CH3 CH3 H3. H3 nudging deatrom elhorphah ;’ a3 a lead compound \' b} a target compound c} a starting material d} a prodrug let all of the above 14. Select an isosteric replacement for an H-atom on the aromatic ring of ephedrine, a decongestent commonly found in nonprescription cold preparations: CH3 IH N. "i. cue, H 3} IF II: 1"r -. Err: .-.-- .1?) -l Irv-lily, ._ '3] 'CH3 d} -NH2 9} -ND; '15. In terms of drug design, structure—activity relationships {BARS} are used by medicinal chemists to e} establish how drugs work b.) discover lead compounds make better drugs by altering the structure of a prototype d} develop prodrugs e}a.b&c . H... I... Iii-Frill?! urn-fl. - . 16. Drugs in the blood stream are generally bound to some extent to serum proteins. e_g_ serum albumin. For drug A, Kn = 4 x ‘lL'i‘5 for drug E1, Kn = flxkjl [)3 __ _. ___ i. at when bound to serum albumin, drugs A s B cannot act at receptors 4:. b} drug B binds more strongly to serum albumin than does drug A c) drugs A 8: B can dissociate from their protein complexes qlwhen both are present. A can significantly increase the activity of B a) 'all of the above 1?. When partitioned between a mixture of octanol and water. drug A's solubility is ! i-D_3.mgme in octanol and E mgHDD mL in water. The value of P for drug A is NJ- a} cos . a} s :23” ' _ b} 0.5 3e) 50 foes- _. ' c] 2i] " I A #25 .y " ' 18. Five drugs have P values as shown. Other factors being equal, the drug absorbed the slowest has the P value 4, y 3‘) cs d} so "b) 1 e} [1? c) 1.5 19. The physicali'chemical properties are a major determining factor in the drug's a] bioayailability b} absorbtion c) distribution d] elimination _ e) all ofthe aboye Ill. 21:]. Drugs can generally cross the blood—brain barrier {BBB}, if they have a} a large yoiume ofdistribution {VD} b] a high partition coefficient {P} c} a long elimination half life {tug} d} a & b --e} a, b 3; c 21. Drug metabolism -. , {:3 a it~ it! ' ' 3’ a a? is carried out mainly in the liver b} is localized in the microsomal subcellular fraction c} makes drugs less lipophilic d’l makes drugs more water soluble ‘3’ e};.al| of the above 22. Cytochrome P45D is a) an enzyme system b) catalyzes the reduction of drugs, as substrates c) contains iron at the active site 23. Drug D-CHz-CHa is metabolized to a mixture of D—CHz—CHz—DH and Ell—CH2— CDDH. x a} the Duatom in the alcohol metabolite originate from H20 b} the {St—atoms in the carboxylic acid metabolite originate from {)2 c] D'CHg-CHTDH can undergo Phase II metabolism .d} b 3‘ c e} a, b a c 24. Metabolic reduction of the anti~inflammatory nambumetone {Relafen} leads to o _ ‘2‘) CH30 !i a a 1°alcohol i Lb , a 2° alcohol F c} a 3" alcohol ' L-llf. d] an aromatic alcohol e) an aldehyde 25. Methylohenidate {Ritalin}. used in the treatment of attention-deficit-hyperactiyity disorder {ADHD}, is hydrglyzed by a metabolic enzyme to HM 5' H I . H D 1%) J a} an alcohol f. b} a carboxylio acid ,5“ l" '1; Leila carboxylic acid and an alcohol 'd) an alcohol and a ketone e} a carboxylic acid and an ester my0 26. Alcoth functional groups that are formed from alkyl- or benzene—group- containing drugs catalyzed by the action of various oxidases, e.g. CYP‘I, CYPZ, lo; CYFS, can serve as attachment points for conjugation reactions. afiTRUE b} FALSE C“ 2?. Phase II glucuronide and sulfate metabolites 1'; .l a] exist mostly as anions in body fluids b} exist mostly as cations in body fluids c} are not reabsorbed by the kidneys to any significant extent _ ;m a and o - 'l‘f-‘r a} b and c 1' ‘5. 28. The procarcinogan benzopyrene is a representative |igid.—s_clu.ble_ polycyclic aromatic hydrocarbon that is commonly found in the enyironment fag, in cigarette smoke}. Its ?,B—diol~El,1El-epoxide metabolite {shown below} is a yery reactiye electrophile. Unless it is further metabolized to the inert marcapturic acid conjugate, it can coyalently modify DNA by reacting with a} the E-amino group of guanine log N-? group of guanine [" c ...the 4-amino group of cytosine d} the E-amino group of adenine a} N-El of thymine 29. Sodium chloramphenicol monosuccinate {CAPS} is NHCCCHCIz D H .5 EH? Ho ENE N0: gas} a prodrug b] suitable for the preparation of concentrated aqueous {intrayenous} dosage forms 5:) activated in w‘yo {in the body} by hydrolysis catalyzed by an esterase {mass i'fé'} a, b a c 30. What is the percentage ofths acid form of nicotine {niootinium ionr R3NH‘), at an intestinal pH of E, if the niootinium ion‘s pKa = B? _ __ II} __ rt t as at = f’» . ' -:..a‘} 999 a I, ~r' We -« p b) as as if it, " c} ass as a” I Hz“ a - a 9.1 s CH: 3 as; e}D_ElEl% J HULL l r uh? ll I "t I” Iu' A" '- .__F-|-1"‘“"_'_' .1613 .thcU= .“L .s. . .- ttvi ta iri.c 31. Kt}. was admitted to hospital following ingestion of an overdose of phenoobarbital It 0 6H: N 04 ‘N H a ct} To help Xfl. eliminate {excrete} phenobarbital via his kidneys you would recommend a] acidifcation of his renal tubular urine b} alkalinization of his renal tubular urine {citric alteration of the pH of his renal tubular urine 32. Tetracycline is an antibiotic useful in the treatment of bacterial infections. CH3 0H Tim-lg: oNH2 H Which of the following statement about tetracycline is false? a'}'its absorption is decreased. when it is taken with calcium-containing substances, e.g. milk. calcium antacids b it forms chelates with divalent metal cations _E}l'it is optically inactive 'd} it has a basic group that can be protonated el'it contains only one aromatic ring 33. The cytotoxicity [cell toxicity] towards cancer cells of a family of nitrogen mustards can be summarized by the equation.“ up .J 7 “FBI H I r log {lidose} = -1 o+1 It 415 n2 +1.3 cit ! r-- Which of the following statement is false? 3} cytotoxicity is related to two properties of the drugs: electronic and lipophilic properties b} there is a nonlinear dependence of the activity on logP c} the transition state for the chemical reaction that takes place is electron rich d} the 'ceil killing chemistry" involves reaction of the mustards with cancer cell DNA to form covalent DNA-mustard products -' e'} the negative coefficient of sigma indicates that mustards with electron withdrawing groups react the fastest with the cancer cell target 34. Acetylcholine, the cholinergic neurotransmitter in the nervous system, can exist in an infinite number of conformations, the most stable of which is a) skew staggered anti c} staggered gauche d} eclipsed e} none of the above 35. Regarding stereochet‘nistnvr which of the following statement is false? .ajr‘moteoules with chiral atoms are optically active .vbj'a 1:1 mixture of enantiomers is a racemate 1; diastereomers are mirror images eoij'n chiral centers in a molecule produce 2” stereoisomers e} restricted rotation about C=C double bonds generates cis and trans geometric isomers BE. Which of the following is true? a} The magnitude of the pharmacological response to a drug may depend on the chiralityr of its stereoisomers, or mayr be indifferent to chiralitjir b) The kind of pharmacological response to a drug may depend on the chirality of its stereoisomers c} Chiral drugs mayr be metabolized to give different metabolites o) a a o a, b 3; c 3?. Folio acid {FA} is a substrate of dihvdrofolate reductase DHFR); methotrexate {MTXJ is an inhibitor of DHFR. Binding to DHFR requires protonation of N—l; the pKa's ofthe protonated molecules are: pK... = 2.35 {FA}; pKa = 5.?1 {MTX}. Which of the following statements is true? 0 H COzH 5T? HES“ CDNH CD?” a. . HQNIIQ‘NI hr” Folic Acid HzN’k‘fi NH Metl'lotrexate 02H 1 f I 02H T ELK-i “I. ' T '- folic acid and methotrexate are isosteres in solutions with a pH of5 there is less folio acid cation {acid} than there is of methotrexate cation {acid} methotrexate binds better [smaller value of the {E-MTX) complex dissociation constant} than does folio acid to DHFR the difference between the pKa of folic acid and methotrexate can be ascribed to electronic (vs. steric] effects all of the above .‘r . J xxx- .1. a} bi C] d] ET". Nil.“ I“: 33. Administration of a second drug that inhibits the metabolism of the first drug may require a decrease in the dose ofthe first drug. V}: “y to -- '- t a} TRUE iii” "m: L ,1 :El'FALSE -. “tit- 39. Induction {turning on the expression] of drug metabolizing enzymes by one drug may require the increase in the dose of another drug that is metabolized by those enzymes. .iif}. '. “if '1' I _ ) TRUE Not-i :1 1y W. at * - _. b FALSE 40. High bioayailability of drugs require H i-I Ilifi 'Il _ a] maximum lipid solubility )k l “mg. no " _~[i,' I : 1|. [bi maximum water solubility . _| W" _ U. i c/i-a balance of water solubility and lipophilicity ff" t' 41. {'12 points total} Draw the structures cfthe indicated metabolites of the anti- infiammatory drug indomethacin. cezcccH CHaC‘ q} t! \ cH3 t? t- N I ci You may answer with clearly drawn abbreyiated structures if you wish. .L. ' a} {E p} The two final oxidatiye D—dgme_t_hylatLoo_products and the intermediate inyolyed .in . - t . Vt J; a, 'V' “H I J'L-i 1 5 It I M. - b} [4 p} The two N—deacylation hydrolysis products fftl-J-r i' ' ' "_'_ '1". 37'.- llt‘~-. '1? "a. .- t that" - - t, .. ’7' " LJL -’ 1.1 '9' {\fl .‘mmn' "J “a. '.:._ k '1 _' J... l t i'_fl':. L I: c} {2 p} The sulfate conjugation product ofthe reaction of PAPS {adenosine- 5'—OPUg—SO§ ] with the demsthyiaticn product obtained question a] nun-H {ll __, 42. (4 points} The anticancer nitrogen mustard cvclophosphamide {Cytoxin®i is a prodrug that becomes metabolicallyr activated by oxidation at the 4-position, which results in ring opening. Draw the structure ofthe product of the initial oxidation and the structure of the ring—opened metabolite {you may abbreviate the structure}. 1 wé: fr ._l.""l_ D '00 E ‘._| II“!-_'I1'I:|l'. !._ 5 EFL—N CH 13 Cl _ _ r 2 I l 2 H: )2 _ J? KEN-H 3: ME i 5 NH :- ' 4 3 . .e'i" " 1\ tr I ma.- 1 .i. 43. {4 points} The following reaction is relevant to Wilson's disease. an inherited disorder. a} Write in all the products of the reaction. Assume that 2 moles of penicillamine and 1 mole of cupric ion react to form the desirable product {stoichiometry is 2:1}. (it. I ". H .- H/S ++ .I cH3 + our") —- .: 1‘: ’I: HEN CDzH b} Name the type {class} of compound formed. when penicillamine and cupric ion react. Answer .-'.'-. '- i'i‘fli - ' l' ijii. -. ...
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This note was uploaded on 12/16/2009 for the course MCH 311 taught by Professor Kalman during the Spring '08 term at SUNY Buffalo.

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Med Chem Exam 1 2000 - Medicinal Chemistry 311"...

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