Medicinal Chemistry 410 Exam #1 February 29, 2008 Name: ‘Med. Chem. # Part. —_(75 Points) ‘There are 50 multiple choice questions worth 1.5 points each (75 Points). Please use the Scantron Sheet provided. 1. The anticancer drug illustrated below: Ba, T reacts with DNA primarily forming an intersirand cross link Cr é Il exhibits greater nephrotoxicity than cisplatin. brn? oO IIT primarily forms adducts with a single strand of helical DNA. a Tonly b — Monly c Tand I only d I and III only e I, I, and IL Answer 2. The drug illustrated below ° ct T__ isa false substrate that mimies p-aminobenzoic aci TI inhibits the De Novo synthesis of folates in bact Ne III_ is used to treat bacterial urinary tract infections (UTIs). a Tonly b. Moly ce Land ITonly d Mand Il only e LMand Il Answer 3. ‘The drug illustrated below has which of the following properties: 1 is recognized for its effectiveness against gram (-) bacteria TL cross allergenicity in patents sensitive to pencillins is fully expected. TIT isused orally. Toaly Monly Land Il only Mand Ill only Land IIL Answer cance4 The drug ilh strated below: I __ is associated with chain termination in the synthesis of viral DNA. IL_ is converted to a mimic of 2'-deoxyadenosine triphosphate. QW IIT is resistant in viruses with a deficieney in viral thymidine kinase. HO-B OH a Tonly b — Mlonly c¢ Tand {only d= Hand ttl only e LIL, and I Answer 5, The drug illustrated below: ct Cl, Ss 9 1 is too unstable for oral administration. reer on 0 primarily cross-links two individual DNA strands, i isa bifunctional alkylating agent. Tonly Mlonly Tand 11 only Mand Ill only LM, and Il Answer 6. The drug illustrated below is NOT orally active. penicillin binding protein (a transpeptidase). x Be I MY TI is B-lactamase resistant. o) IIL inhibits bacterial cell wall synthesis by inhibiting hh fs Mand Ill only 1. 1l,and Il Answer 1 The ug illustrated below: il c> He 1. isa potent antifungal agent. II binds to the heme portion of a specific cytochrome P450. 160. cH TIT isan aromatase inhibitor. oars Tonly Monly Vand II only Mand III only 1M, and I Answer8.___ The drug illustrated below Oo! ae 1 isamitotic spindle poison ¥ e TL is asubstrate for the efflux transporters MDR1 and BCRP. \, | HIE stabilizes the cleaved complex formed from topoisomerase and DNA. Hea ER, a Tonly b — Hfonly ce Land only d Mand Illonly © Mand ill Answer 9, ‘The drug illustrated below: Nis r, I inhibits dihydrofolate reductase in bacteria Hg Ne I iimeversibly inhibits the enzyme thymidylate synthetase. ae TIL _ blocks protein synthesis by binding to ribosomal RNA. wicd “oo, a Tonly b — Mfonly © Land Ilonly 4 Mand Illonly e 1, II, and IIL Answer: 10. The drug illustrated below 9 ae T_ blocks androgenic receptors. w? S8 «pF II has been used to treat prostate cancer IIL inhibits Sa-reductase, the enzyme which reduces testosterone to Sa-dihydrotestosterone. a only b — Mfonly c Land Ionly d Mand Ilfonly e Land Ut Answer LL The drug illustrated below eaece Lys I is used in monotherapy (single-agent therapy) of HIV infection, ] II is NOT cross-resistant with nucleoside reverse transcriptase inhibitors. Oy ou, | HI is anon-competitve inhibitor of reverse transcriptase Oo Tonly MI only Land IT only Mand IIT only 1.1, and IIT Answer12.__ The drug illustrated below: NN T is leucovorin and is used in “rescue therapy” Lu oO ee IL inhibits DNA synthesis by limiting the DeNovo synthesis y Ay, of thymidine. ape IIT inhibits dihydofolate reductase. a Tonly b — Ionly c Tand I only d Hand Ill only e 1,1, and IT Answer 13. _ The drug illustrated below: 1 A... 1 isaprodmug. eee TI is B-lactamase resistant. L HIT can be administered orally a Tonly b — Monly ¢ Land Ionly d= Mand If only e — Llland Ir Answer 14. The drug illustrated below: I has been used to prevent breast cancer in high risk HoH, individuals. i IL is an estrogen receptor antagonist. conan TIT inhibits the synthesis of estrogen. a Tonly b — IMonly c Land I only d Mand Il only e LMland iit Answer 15,__ The drug illustrated below: Wa I _isused in combination with the thymidine mimic, Zidovudine (AZT). TE does cause chain termination of developing viral DNA. | TET is effective against RNA-containing viruses. HoH a Tonly b — Monly ¢ Land Ionly d Hand Itt only e 1,01, and I Answer16, _ The drug illustrated below: 17, _The drug illustrated below is: O. & T can only be administered intravenously. Ci N(CH,CH,CI), IL isabifunctional alkylating agent. NH TII__isassociated with hemomhagic cystitis a Tony b Il only c Tand II only d= Hand IHonly © 1,01, and II Answer oH, Soe 1 isa bacterial protein synthesis inhibitor. MH isactive orally. TH is B-lactamase resistant. a b c d e © Tonly M only Land Il only Mand Ill only 111, and IN 18. _The drug illustrated below: 1H, cH I_ isan oral contraceptive. + IL isan estrogenic steroid. 4 IIT has a 11f-hydroxyl group. a Tonly b M1 only © land I only d= Wand II only © Glland il Answer 19. The drug illustrated below: 1. docs NOT require oxidative metabolism, but only hydrolysis to be active. IL can cause hemorthagic cystitis as a side effect. ty ov III isa bifunctional alkylating agent. ba anes Tonly Ut only Tand I only Mand IT only 1,11, and 11 Answer20. The drug illustrated below: 1 _isconverted to its 2”-deoxyribosylmonophosphate IL_ ultimately can irreversibly bind to and inhibit thymidylate synthetase. IIT is associated with photosensitivity. a_Tonly b Monly c¢ Land Ilonly d Wand Illonly e — Llland Il Answer 21. _The drug illustrated below o COsH | 1 initially blocks protein synthesis in bacteria, 4 J II has inhibitory activity on bacterial cell wall synthesis. 4 N NY III targets the enzyme DNA gyrase and converts it into a oo cellular poison. im Tonly Ur only Land II only Mand IIT only 1. M,and IIT Answer 22. _The drug illustrated below: HG SH sch, T__ has been used to treat hair loss (alopecia) in males, II has been used to treat benign prostatic hyperplasia. TIT acts as a competitive inhibitor Sa-reductase activity. 23. _‘The drug illustrated below: Tonly Mtonly Land Il only Mand It only 1, II, and IIL Answer ° Tis used to treat tuberculosis wromonnt€Y-cravinicts Tl is amonofunctional alkylating agent. IM __ requires metabolic activation. eaoce Tonly Ionly Tand Il only Mand III only 1, Hand IIT Answer24, ~ The drug illustrated below H.C, 1 isa protein tyrosine kinase inhibitor. IL is used to treat hepatocellular carcinoma. III targets Rafkinase, PDGF, c-Kit, and VEGER (-2 & -3). a Tonly b — Monly c Land Honky d= Mand 11 only e Landi Answer 25. __ The drug illustrated below is: HoH NON. CHs | | isactivated to an inhibitor of dihydrofolate reductase. NH NH GH, | IH isused in combination therapy to prevent the parasitic disease, malaria IH stimulates L-asparaginase in cancer therapy a Tonly b — Mlonly c Land only dad Ilfonly e — IMland Ill Answer 26. _‘The drug illustrated below is I apotent mineralocorticoid MH hasan 11f-hydroxyl group. HI among the more potent glucocorticoids. a Tonly b I only c Land Tl only d Mand Ilfonly e 1 l,and IIL Answer 27. ‘The drug illustrated below: car") I acts by targeting topoisomerase IL Loe CY IL isknown to exhibit cardiac toxicity. i TIL extravasation of this agent is associated with severe 7 necrosis at the site of infusion. Tonly IE only Land IT only Mand IIT only 1. Il, and IIT Answer‘The drug illustrated below u «ts on ct i isa 2'deoxycytosine mimic isa prodrug. of cS TIT requires phosphorylation by viral thymidine kinase for activity uN. CHC a Tony b — Monly © Land Ionly d= Hand IT only e 1, I, and HL Answer 29. The drug illustrated below 2 (CIHCH2CN—C-NCH-CH,CI eis is associated with nausea and vomiting is transformed into’ two different monofunctional alkylating agents. is used to treat brain tumors a Tonly b — Mfonly © Land Ionly d— Mand Ill only eI Iland ll 30.__ The drug illustrated below Answer i: T_ binds to ergosterol and disrupts the cell membrane of fungi IL is used systemically. OF rey TIL inhibits 14a-demethylase in the biosynthesis of ergosterol. Ne a Tonly b Ionly c Land Il only d I and IIT only © 1, I, and IL Answer 31. The drug illustrated below: Ea He? 1 we. isa non-nucleoside reverse transcriptase inhibitor. IL isa HIV protease inhibitor. & a O IIL acts asa “transition state” enzyme inhibitor. a Tonly b — Mfonly © Land Ionly d— Mand Ill only e I Mand lt Answer— awrvernrirew \y veue 33. bo enece N, AN | im afbtactamase i )OH_ I ahighly effective Gram (-) antibiotic I orally active, Tonly Monly Land IL only Mand 111 only 1.11, and IIE Answer Avastin” Bevacizumab, u m isan antibody that binds to the receptor for vascular endothelial growth factor. isa humanized monoclonal antibody, prevents the vascularization (endothelial cell growth) that is associated with tumor growth a Tonly b Monty c Land Honly q Mand I only 1 and IIE Answer 34.__The drug illustrated below: Lo 1 is lethal ifadministered by intrathecal injection. Reon TE acts as a mitotic spindle poison by destabilizing ij microtubules and promoting their dissolution, i Conon | TT acts as a mitotic spindle poison by inhibiting the Toco disassembly of microtubules ee pe i a Tonly b Monly © Land Ionly d Mand only eI, Mand Ill Answer 35.__ The drug illustrated below: 1 isa suicide substrate TL —_isanon-competitive and an irreversible inhibitor. 1 an antagonist fr the aromatase receptor associated with stimulating estrogenic activity in mammalian breast tumor cells, Tonly Mt only Vand Il only Wand I1f only 1.11, and IIT Answer ___36. The drug illustrated below ° HN’ N I ultimately acts as a guanosine mimic. ee ul is incorporated into viral DNA. roy WW is synergistic with AZT (a thymidine mimic), i a Tony b — Monly © Tand only d—— Tand Ionly e 1, Il, and IIL Answer: 31.__The drug illustrated below FF co Heal " H,04) CH CH, T_ has limited clinical use because of its short halflife. 1 ' K By IL cannot form the ketal intermediate at low pH that isassociated with cs och _| the stomach cramping of other macrolide antibiotics. cHscuf totes IIT isnot crossallergenic with penicillin antibiotics, oH g on ne a Tomy b — Monly c Land Honly d= Mand ITonly e I, IL, and IIL Answer 38. Acute Asus 1 is uncontrolled growth of B- or T-lymphocytes Lomhoestic TI is the most common of childhood leukemia, Leukemia (ALL) | 17 js she uncontrolled growth of granulocytes. a Tory b Monly © Land Honly d Wand ITonly e 1, II, and IIL Answer: 39.__ The drug illustrated below Land Il only Mand IIT only 1, Il, and IIT eaoce I is a metabolite of estrogen. 1 is used to increase fertility m1 is the second most potent androgenic metabolite of testosterone. Toaly Utonly Answer40.__ The drug illustrated below is: wel to prevent hemorshagic cystitis associated with the inistration of eyelophosphoramide. anes, TI activated by alkaline phosphatase. 4 HO TH used to prevent renal toxicity associated with the administration of cisplatin. a only b — Mlonly © Land fl only 4 Tand If only e — Llland Ill Answer 41. The drug illustrated below: Gy OH 1 hasan anabolic:androgenic ratio of 3:1 Il _ isanorally active synthetic estrogen. TIT isan aromatase inhibitor. a only b — IMlonly © Land Honly d Mand IH only e LM,and Il Answer 42. _The drug illustrated below: 5 1 Isa potent glucocorticoid. s u Is a potent mineralocorticoid. m Isused as an abortifacient. a Tonly b — Mlonly c Land Ionly d= Tand Il only e Ill,and tl Answer 43. The drug illustrated below: Rituximab, T is a monoclonal antibody used to treat metastatic breast cancers that Rutuxin® overexpresses human epidermal growth factor 2, HER2. TE acts as an antiangiogenic agent to prevent the production of new blood vessels IIT is used in the treatment of non-Hodgkin’s lymphoma that possess the membrane bound phosphoprotein, CD-20. Tonly Honly Tand [I only Hand Ill only 1,11, and ML Answer nr eacgeDB 44, The drug illustrated below is: 1 converted to iis disulfide im the Kidney and then rapidly eliminated in urine to IL used to prevent hemorrhagic cystitis that is commonly associated with the & administration of cyclophosphoramide. II1_ rapidly converted to its disulfide in the bloodstream. a Tonly b — ILonly © Land Tl only d e HS—CH,-CH, Wand II only 111, and IL Answer 45.__The drug illustrated below: a aecces I inhibits squalene epoxidase in the synthesis of ergosterol. OH I cannot be used orally, but is effective topically for Tinea infections. IIT inhibits 14a-demethylase in the biosynthesis of ergosterol. a Tonly b — Mfonly c Land only d Mand Iltonly e [land ill Answer 46.__ The drug illustrated below is: oe oF I binds to ergosterol producing an antifungal effect. i known to induce cytochrome P450 enzymes, such as CYP450 3A4. IIT Binds to mycobacterial DNA. dependent RNA polymerase. Tonly Ml only Tand Il only Mand IIT only 1, Hand IIL Answer eneces 47. The drug illustrated below: I rarely is associated with allergies. IL can discolorand retard growth of developing teeth in children. TIL can be administered orally. a Tonly b — HFonly © Land H only d= Mand 11 only e [land 1Ir Answer48. The drug illustrated below: NH is used in combination with nucleoside reverse transcriptase inhibitors that mimic thymidine or 2'-deoxycytosine. fun NN I must beconverted toa 5’-triphos Hone IIL is metabolically converted toa n late to be active. of 2"-deoxyguanosine. Tonly ML only Land II only Mand IIT only 1. I,and IIL Answer 49. The drug illustrated below: noose I is an orally active peptide, IL isa gonadotropin-releasing hormone agonists (GnRH) IIL is used to treat advanced prostate cancer, Tonly Moaly and Il only Mand Ill only 1.11, and Ill Answer 50. The drug illustrated below: T binds to CCRS and prevents interaction with gp120 acting asa chemokine receptor antagonist. IL is orally active IH] is an entry inhibitor preventing HIV entry into non-infected human T cells, a Tonly b — Hlonly ¢ Land Ilonly d Mand Ilfonly © Land iit Answer Part 2 Generic Names (9 Points), Provide the Generic Names for the Compounds listed on the following page. In the space provided under the structure of each the compounds illustrated, write the correct CAPITALIZED letter corresponding to the choice of answers given on the bottom of the page. The letter “Z” may be used as an answer as seldom or as often as needed.HQ ocHs CoH aE we 4 oye _CHOH tyr ° S/ ‘ocr 7 “crobcH, NY os COOH Answer ° . ot me cH ROO a Ho, ee ns ae At 10, 4 ww = ES = g Answer Answer Answer TP oH Eee HNO Nes ES CHS i ceo gncHt, 4 S ma} oy J CHs cooH 5 ww! HO Answer ___ Answer Answer £ oe x ‘ ‘| . hic? pH pHeH, ‘ Kokoro f —~y Ze Ney 8 e ji Answer asec Answer ‘A. Cofotaxime J. Mitepristone S. Dacarbazine B. Etoposide K. Testosterone T. Dexrazone C. Clavulanie acid L. Amoxicillin U. Aldosterone D. Doxyeyeline M. Zidovudine V. Piperacillin E. Betamethazone N. Finasteride W, Levofloxacin F, Topotecan ©, Meropenem X. Ritonavir G. Tobramycin P. Trimethoprim ¥. Voriconazole AH. Terbinafine Q. Ribavirin Z. None of These L Sulfadoxine R. OseltamivirPart 3 Nomenclature 16 Points. ‘When using the basic templates provided insert all unsaturation as required and specify the orientation of all functionality or hydrogen atoms by using BOLD lines/wvedges or HASHED- lines/wedges. Example Hs OR 1. Pregna-1,4-diene-3,20-dione, 1 IP-hydroxy-6a-methyl [known as Endrysone] z 8 Cy 2. $-Thia-1-azabieyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-{[amino(2- bromophenyl)acety!Jamino]-8-oxo-3-( |-propenyl)-, [68-[6ct,7B(S* )]]-16 3, OF-Purine-6-one, 2-amino-1,9-dihydra-I-ethyl-9-[2-hydroxy-1-(fiuoromethyl}ethoxy]methyl 4. 3-Quinoline carboxylic acid, 6-fuoro-1-(4-fluorophenyl)-1,4-dihydro-4-ox0-7-(1- piperazinyl)-, monohydrochloride [known as Sarafloxacin] Exam Total: Part |. Multiple Choice 75 Points Part 2. Generic Names 9 Points Part 3. Nomenclature 16 Points Total