Medicinal chemistry exam 1
Transcript of Medicinal chemistry exam 1
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Medicinal Chemistry 410 Exam #1 February 29, 2008 Name: Med. Chem. #
Part I. (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:
NH2
NH2
PtO
O
O
OH
H
I reacts with DNA primarily forming an interstrand cross link. II exhibits greater nephrotoxicity than cisplatin. III primarily forms adducts with a single strand of helical DNA.
a I only b III only c I and II only d II and III only e I, II, and III Answer
2. The drug illustrated below:
SO
ONH
H2NN O
CH3
I is a false substrate that mimics p-aminobenzoic acid. II inhibits the De Novo synthesis of folates in bacteria.
III is used to treat bacterial urinary tract infections (UTI’s). a. I only b. III only c. 1 and II only d. II and III only e. I, II, and III Answer
3. The drug illustrated below has which of the following properties:
NO
CH3
H
H
HN
O
NOCH3C CH3C
NS
H2N
SO3
NaO
O
I is recognized for its effectiveness against gram (-) bacteria II cross allergenicity in patents sensitive to pencillins is fully expected. III is used orally.
a I only b III only c I and II only d II and III only
e I, II, and III Answer
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4. The drug illustrated below:
N
N N
N
NH2
OPO
HOOH
I is associated with chain termination in the synthesis of viral DNA. II is converted to a mimic of 2’-deoxyadenosine triphosphate. III is resistant in viruses with a deficiency in viral thymidine kinase.
a I only b III only c I and II only d II and III only e I, II, and III Answer
5. The drug illustrated below:
N CH2CH2CH2C
Cl
ClO
OH
I is too unstable for oral administration. II primarily cross-links two individual DNA strands. III is a bifunctional alkylating agent.
a I only b III only c I and II only d II and III only e I, II, and III Answer
6. The drug illustrated below:
NO
NH
HO
S
CO2
CH2
H
NO
NS
H2N
N
CH3H3C COOH
I is NOT orally active. II is β-lactamase resistant. III inhibits bacterial cell wall synthesis by inhibiting penicillin binding protein ( a transpeptidase).
a I only b III only c I and II only d II and III only e I, II, and III Answer
7. The drug illustrated below:
I. is a potent antifungal agent. II binds to the heme portion of a specific cytochrome P450. III is an aromatase inhibitor.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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8. The drug illustrated below:
NN
O
OH3CH2C OH
OO
H2CCH3
N
N
O
I is a mitotic spindle poison. II is a substrate for the efflux transporters MDR1 and BCRP. III stabilizes the cleaved complex formed from topoisomerase I and DNA.
a I only b III only c I and II only d II and III only e I, II, and III Answer
9. The drug illustrated below:
NN
NH2
NH2H2C
H3CO OCH3
OCH3
I inhibits dihydrofolate reductase in bacteria. II irreversibly inhibits the enzyme thymidylate synthetase. III blocks protein synthesis by binding to ribosomal RNA.
a I only b III only c I and II only d II and III only e I, II, and III Answer
10. The drug illustrated below:
I blocks androgenic receptors. II has been used to treat prostate cancer. III inhibits 5α-reductase, the enzyme which reduces testosterone to 5α-dihydrotestosterone.
a I only b III only c I and II only d II and III only e I, II, and III Answer
11. The drug illustrated below:
N
N
NN
O HCH3
I is used in monotherapy (single-agent therapy) of HIV infection. II is NOT cross-resistant with nucleoside reverse transcriptase inhibitors. III is a non-competitive inhibitor of reverse transcriptase.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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12. The drug illustrated below: I is leucovorin and is used in “rescue therapy”. II inhibits DNA synthesis by limiting the DeNovo synthesis of thymidine. III inhibits dihydofolate reductase.
a I only b III only c I and II only d II and III only e I, II, and III Answer
13. The drug illustrated below:
NO
NH
HO
S
CCH2OCONH2
H
N
O
O
O CH3
CH3O
OOCH3
I is a prodrug. II is β-lactamase resistant. III can be administered orally.
a I only b III only c I and II only d II and III only e I, II, and III Answer
14. The drug illustrated below:
CH2CH3
OCH2CH2NCH3
CH3
I has been used to prevent breast cancer in high risk individuals. II is an estrogen receptor antagonist. III inhibits the synthesis of estrogen.
a I only b III only c I and II only d II and III only e I, II, and III Answer
15. The drug illustrated below:
N
N
OO
S
NH2
HOH2CH H
I is used in combination with the thymidine mimic, Zidovudine (AZT). II does cause chain termination of developing viral DNA. III is effective against RNA-containing viruses.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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16. The drug illustrated below:
NHP
O O
N(CH2CH2Cl)2
I can only be administered intravenously. II is a bifunctional alkylating agent. III is associated with hemorrhagic cystitis.
a I only b III only c I and II only d II and III only e I, II, and III Answer
17. The drug illustrated below is:
OH OHOH
O
NH2
O
OH
N(CH3)2HHO CH3
O
H I is a bacterial protein synthesis inhibitor. II is active orally. III is β-lactamase resistant.
a I only b III only c I and II only d II and III only e I, II, and III Answer
18. The drug illustrated below:
HOH
H
H
OHC CH
CH3 I is an oral contraceptive. II is an estrogenic steroid. III has a 11β-hydroxyl group.
a I only b III only c I and II only d II and III only e I, II, and III Answer
19. The drug illustrated below:
I does NOT require oxidative metabolism, but only hydrolysis to be active. II can cause hemorrhagic cystitis as a side effect. III is a bifunctional alkylating agent.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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20. The drug illustrated below:
HN
NH
OF
O
I is converted to its 2’-deoxyribosylmonophosphate. II ultimately can irreversibly bind to and inhibit thymidylate synthetase. III is associated with photosensitivity.
a I only b III only c I and II only d II and III only e I, II, and III Answer
21. The drug illustrated below:
N
OCO2H
N
F
OCH3N
H
H
H
I initially blocks protein synthesis in bacteria. II has inhibitory activity on bacterial cell wall synthesis. III targets the enzyme DNA gyrase and converts it into a cellular poison.
a I only b III only c I and II only d II and III only e I, II, and III Answer
22. The drug illustrated below:
NH
CH3
H
H H
CH3H
O
HNO
CH3C
CH3
CH3
H
I has been used to treat hair loss (alopecia) in males. II has been used to treat benign prostatic hyperplasia. III acts as a competitive inhibitor 5α-reductase activity.
a I only b III only c I and II only d II and III only e I, II, and III Answer
23. The drug illustrated below:
CH2NHNHCH3(H3C)2HCHNCO I is used to treat tuberculosis.
II is a monofunctional alkylating agent. III requires metabolic activation.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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24. The drug illustrated below:
O
N N
O
NNH
O
Cl
CF3
H3C
H H
I is a protein tyrosine kinase inhibitor. II is used to treat hepatocellular carcinoma. III targets Raf kinase, PDGF, c-Kit, and VEGFR (-2 & -3).
a I only b III only c I and II only d II and III only e I, II, and III Answer
25. The drug illustrated below is:
I is activated to an inhibitor of dihydrofolate reductase. II is used in combination therapy to prevent the parasitic disease, malariaIII stimulates L-asparaginase in cancer therapy.
a I only b III only c I and II only d II and III only e I, II, and III Answer
26. The drug illustrated below is:
CH
H
H H
CH3H
O
O
OH
HO
O
I a potent mineralocorticoid. II has an 11β-hydroxyl group. III among the more potent glucocorticoids.
a I only b III only c I and II only d II and III only e I, II, and III Answer
27. The drug illustrated below:
OCH3
CH2OH
O
OH
O
OH3C
OHNH2
O
O OH
I acts by targeting topoisomerase II. II is known to exhibit cardiac toxicity. III extravasation of this agent is associated with severe necrosis at the site of infusion.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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28. The drug illustrated below:
HN
N N
N
OO
O
H2N
CONH2
CH(CH3)2H
CH2OH
I is a 2’deoxycytosine mimic. II is a prodrug. III requires phosphorylation by viral thymidine kinase for activity.
a I only b III only c I and II only d II and III only e I, II, and III Answer
29. The drug illustrated below:
C NCH2CH2ClClH2CH2CNO
H N O
I is associated with nausea and vomiting. II is transformed into two different monofunctional alkylating agents. III is used to treat brain tumors
a I only b III only c I and II only d II and III only e I, II, and III Answer
30. The drug illustrated below:
NN
N
F
F
OHN
N
N
I binds to ergosterol and disrupts the cell membrane of fungi II is used systemically. III inhibits 14α-demethylase in the biosynthesis of ergosterol.
a I only b III only c I and II only d II and III only e I, II, and III Answer
31. The drug illustrated below:
I is a non-nucleoside reverse transcriptase inhibitor. II is a HIV protease inhibtor. III acts as a “transition state” enzyme inhibitor.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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32. The drug illustrated below is:
N
S
O
CH3
CH2
COOH
H O O
N NN
I a highly effective Gram (-) antibiotic. II orally active. III a β-lactamase inhibitor.
a I only b III only c I and II only d II and III only e I, II, and III Answer
33. Bevacizumab, Avastin®
I is an antibody that binds to the receptor for vascular endothelial growth factor. II is a humanized monoclonal antibody. III prevents the vascularization (endothelial cell growth) that is associated with tumor growth
a I only b III only c I and II only d II and III only e I, II, and III Answer
34. The drug illustrated below:
N
NC O
H
N
HOCH2CH3
CO2CH3
H
N
H
CH2CH3
OCOCH3
OHCO2CO3
H
I is lethal if administered by intrathecal injection. II acts as a mitotic spindle poison by destabilizing microtubules and promoting their dissolution. III acts as a mitotic spindle poison by inhibiting the disassembly of microtubules.
a I only b III only c I and II only d II and III only e I, II, and III Answer
35. The drug illustrated below:
I is a suicide substrate. II is a non-competitive and an irreversible inhibitor. III an antagonist for the aromatase receptor associated with stimulating estrogenic activity in mammalian breast tumor cells.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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36. The drug illustrated below
HN
N N
N
OHOH
O
I ultimately acts as a guanosine mimic. II is incorporated into viral DNA. III is synergistic with AZT (a thymidine mimic).
a I only b III only c I and II only d II and III only e I, II, and III Answer
37. The drug illustrated below:
O
N
CH3
CH3
CH3
CH3O
H3C
H3CH3C
HO
CH3CH2
HOO
O
OH3C
OH
OCH3
CH3
CH3
NCH3H3C
O
I has limited clinical use because of its short half-life. II cannot form the ketal intermediate at low pH that is associated with the stomach cramping of other macrolide antibiotics. III is not cross allergenic with penicillin antibiotics.
a I only b III only c I and II only d II and III only e I, II, and III Answer
38.
Acute Lymphocytic Leukemia (ALL)
I is uncontrolled growth of B- or T-lymphocytes. II is the most common of childhood leukemia III is the uncontrolled growth of granulocytes.
a I only b III only c I and II only d II and III only e I, II, and III Answer
39. The drug illustrated below:
OHCH3
H
HHHO
OH
I is a metabolite of estrogen. II is used to increase fertility. III is the second most potent androgenic metabolite of testosterone.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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40. The drug illustrated below is:
H2N NS
PO
OHHOH
I used to prevent hemorrhagic cystitis associated with the administration of cyclophosphoramide. II activated by alkaline phosphatase. III used to prevent renal toxicity associated with the administration of cisplatin.
a I only b III only c I and II only d II and III only e I, II, and III Answer
41. The drug illustrated below:
I has an anabolic:androgenic ratio of 3:1. II is an orally active synthetic estrogen. III is an aromatase inhibitor.
a I only b III only c I and II only d II and III only e I, II, and III Answer
42. The drug illustrated below:
CH3
CH3HOH
F H
O
O
O
O
O
O
I Is a potent glucocorticoid. II Is a potent mineralocorticoid. III Is used as an abortifacient.
a I only b III only c I and II only d II and III only e I, II, and III Answer
43. The drug illustrated below: Rituximab, Rutuxin®
I is a monoclonal antibody used to treat metastatic breast cancers that overexpresses human epidermal growth factor 2, HER2. II acts as an antiangiogenic agent to prevent the production of new blood vessels. III is used in the treatment of non-Hodgkin’s lymphoma that possess the membrane bound phosphoprotein, CD-20.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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44. The drug illustrated below is:
CH2HS CH2 SO
OO
Na
I converted to its disulfide in the kidney and then rapidly eliminated in urine. II used to prevent hemorrhagic cystitis that is commonly associated with the administration of cyclophosphoramide. III rapidly converted to its disulfide in the bloodstream.
a I only b III only c I and II only d II and III only e I, II, and III Answer
45. The drug illustrated below:
C C CCH3
CH3CH3
NCH3
I inhibits squalene epoxidase in the synthesis of ergosterol. II cannot be used orally, but is effective topically for Tinea infections. III inhibits 14α-demethylase in the biosynthesis of ergosterol.
a I only b III only c I and II only d II and III only e I, II, and III Answer
46. The drug illustrated below is:
CH3
CH3CH3
OH
HO
CH3H3CCO
CH3H3CO
O
O
O
O
O
NH
N N N CH3
OHH3C
CH3
O
O
I binds to ergosterol producing an antifungal effect. II known to induce cytochrome P450 enzymes, such as CYP450 3A4. III Binds to mycobacterial DNA dependent RNA polymerase.
a I only b III only c I and II only d II and III only e I, II, and III Answer
47. The drug illustrated below:
OH OHOH
O
NH2
O
OH
N(CH3)2HHO CH3
O
H
I rarely is associated with allergies. II can discolor and retard growth of developing teeth in children. III can be administered orally.
a I only b III only c I and II only d II and III only e I, II, and III Answer
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48. The drug illustrated below:
N
N N
N
NH
H2N
HOH2C
I is used in combination with nucleoside reverse transcriptase inhibitors that mimic thymidine or 2’-deoxycytosine. II must be converted to a 5’-triphosphate to be active. III is metabolically converted to a mimic of 2’-deoxyguanosine.
a I only b III only c I and II only d II and III only e I, II, and III Answer
49. The drug illustrated below:
I is an orally active peptide. II is a gonadotropin-releasing hormone agonists (GnRH) III is used to treat advanced prostate cancer.
a I only b III only c I and II only d II and III only e I, II, and III Answer 50. The drug illustrated below:
I binds to CCR5 and prevents interaction with gp120 acting as a chemokine receptor antagonist. II is orally active. III is an entry inhibitor preventing HIV entry into non-infected human T cells.
a I only b III only c I and II only d II and III only e I, II, and III 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.
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SO
ONH
H2NN
N
OCH3H3CO
Answer
N
OCO2H
NN
H3C
F
O CH3H
Answer
OHCH3
H
H HO
CH3
Answer
OH OHOH
O
NH2
O
OH
N(CH3)2HH CH3
O
H
HOH
Answer
NO
COOH
HH3C
HOH S
H
NH
H
ON
CH3
CH3H
CH3H
Answer
N N CH2H CH CH3
NN
O
OH
O
O
Answer
S
NH3C
H3C
N
O
N
CH3H3C
O
N N
O
O
N
S
CH3 H
H
OH H
Answer
NO
NH
HO
S
CO2
CH2OCCH3
H
NOCH3
NS
H2N
O
NaAnswer
Answer
Answer
O
O
H2NH2C
NH2
H2N
O
NH2
OOH
H2N
HO
HO
HOHOCH2
6'
Answer
Answer
Answer
C C CCH3
CH3CH3
NCH3
Answer
N
S
O
NH
HCH3
CH3
COOH
O
CH
HO
H2N
H
Answer
NN
FCH3
N
NN
F
F
OH
Answer
N
N
O
O
CH3H
O
N3
HO
CH3
N
Answer
OHCH3
H
HO
C C
H3C
CH3
Answer
A. Cefotaxime J. Mifepristone S. Dacarbazine B. Etoposide K. Testosterone T. Dexrazone C. Clavulanic acid L. Amoxicillin U. Aldosterone D. Doxycycline M. Zidovudine V. Piperacillin E. Betamethazone N. Finasteride W. Levofloxacin F. Topotecan O. Meropenem X. Ritonavir G. Tobramycin P. Trimethoprim Y. Voriconazole H. Terbinafine Q. Ribavirin Z. None of These I. Sulfadoxine R. Oseltamivir
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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/wedges or HASHED lines/wedges. Example
CH3
H
OR
H3C
H
NOT
CH3
H 1. Pregna-1,4-diene-3,20-dione, 11β-hydroxy-6α-methyl [known as Endrysone]
2. 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[amino(2-
bromophenyl)acetyl]amino]-8-oxo-3-(1-propenyl)-, [6S-[6α,7β(S*)]]-
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3. 6H-Purine-6-one, 2-amino-1,9-dihydro-1-ethyl-9-[2-hydroxy-1-(fluoromethyl)ethoxy]methyl
4. 3-Quinoline carboxylic acid, 6-fluoro-1-(4-fluorophenyl)-1,4-dihydro-4-oxo-7-(1-
piperazinyl)-, monohydrochloride [known as Sarafloxacin]
N Exam Total: Part 1. Multiple Choice 75 Points
Part 2. Generic Names 9 Points
Part 3 Nomenclature 16 Points
Total