I is a cascading prodrug. II is used to treat hepatitis B infection III ultimately inhibits viral reverse transcriptase.

Transcription

1 Medicinal Chemistry 410 Exam #1 February 19, 2010 ame: Med. Chem. # 1 Part. (75 Points) There are 50 multiple choice questions worth 1.5 points each (75 Points). Please use the cantron heet provided. f you feel there is no correct answers, leave the cantron blank for that particular question and write E on your exam for that question. 2 C 1. The drug illustrated below: P 2 C C 2 C 3 C C 3 C 3 C C The drug illustrated below: 2 2 C 3 is a cascading prodrug. is used to treat hepatitis B infection ultimately inhibits viral reverse transcriptase. can be used synergistically with sulfonamide anitbiotics. selectively inhibits dihydrofolate reductase in protozoa relative to bacteria. is used to treat malaria. 3 C C 3 3. The drug illustrated below: is very effective against anerobic bacteria. is primarily used against Gram (-) bacteria. binds to the 16 ribosomal portion of the 30 ribosomal subparticle.

2 4. The drug illustrated below: 2 Cl Cl C3 C 3 C 3 C is orally active. is β-lactamase resistant. inhibits bacterial cell wall synthesis by inhibiting penicillin binding protein (a transpeptidase). 5. The drug illustrated below: F F. inhibits squalene epoxidase. can be used iv for systemic fungal infection. inhibits C-14α-demethylase. 6. The drug illustrated below: 3 C C 3 2 a. only b. only c. 1 and only d. and only e.,, and 7. The drug illustrated below: is a competitive inhibitor of the synthesis of dihydropteroic acid. blocks the De ovo synthesis of dihydrofolate in bacteria. has a long duration of action making it useful in the treatment of protozoal infections. is classified as a nucleoside reverse transcriptase inhibitor. does cause chain termination of developing viral DA. is used in combination with the 2 -deoxycytidine mimic, Lamivudine.

3 8. The drug illustrated below: 3 C C 3 C C 3 C 3 is resistant to β-lactamase. is administered with cliastin to prevent deactivation by renal dehydropeptidase. is administered orally The drug illustrated below: 3 C 3 C 3 C C 3 C 3 is used together with other V protease inhibitors. is known to inhibit CYP 3A4 and CYP 2D6 enzymes. is a component of Kaletra. 10. The drug illustrated below: C 3 (C 3 ) 2 degradation products found in expired lots of this drug can be highly nephrotoxic. 2 binds to the 23 ribosomal RA of the 50 subunit. is sensitive to β-lactamase. 11. The drug illustrated below: is classified as a non-nucleoside reverse transcriptase inhibitor. is effective orally. is used as a prophylactic to prevent malarial infection.

4 12. The drug illustrated below: C 3 3 C 3 C 3 C 3 C 2 C C 3 C 3 3 C C 3 C 3 3 C C 3 C 3 C 3 binds to the 50 subunit of ribosomal RA of bacteria disrupting protein synthesis. can readily undergo internal ketalization under acid conditions must be enteric coated for oral administration The drug illustrated below: 2 C C 2 2 C(C 3 ) 2 is a 2 deoxyadenosine mimic. is a prodrug. inhibits viral DA polymerase. 14. The drug illustrated below: is only effective by iv administration. is a carbapenem antibiotic. is an inhibitor of β-lactamase. 15. The drug illustrated below: The drug illustrated below: inhibits squalene epoxidase in the synthesis of ergosterol in fungi. cannot be not used orally, but is effective topically for Tinea infections. is used as a prophylactic for malarial infection.

5 16. The drug illustrated below: 5 C 3 is a competitive inhibitor of reverse transcriptase competing with deoxynucleoside triphosphates for incorporation into viral DA. is used to treat DA viral infections such as erpes implex infection. is susceptible to the development of resistance when used as monotherapy. 17. The drug illustrated below: is a prodrug. C 3 C 2 C 2 C is effective orally is β-lactamase resistant. C 3 C The drug illustrated below: 16. The drug illustrated below: blocks the integration of viral genetic material into human chromosomes. is effective orally. is used in the prophylactic treatment for malaria. is used to treat hepatitis B infections. is activated to its 5 -triphosphate. inhibits viral reverse transcriptase.

6 17. The drug illustrated below: 6 is a third generation cephalosporin is β-lactamase resistant. is effective orally. 18. The drug illustrated below: C C C 3 C 3 C is more active than ampicillin toward Gram (-) bacteria such as Pseudomonas aeroginosa. is resistant to β-lactamase is a prodrug. 19. The drug illustrated below: F C 3 C 2 initially blocks protein synthesis in bacteria. primarily kills gram (+) bacteria. can cause double-strand breaks in bacteria DA. 20. The drug illustrated below: C 3 C 2 C is a potent broad spectrum antibiotic that can kill gram (-) bacteria. is not orally effective and must be administered parenterally. is a β-lactamase inhibitor.

7 3 C 21. The drug illustrated below: 3 C C C The drug illustrated below: lacks the cross resistance observed among several nucleoside reverse transcriptase inhibitors (RTs). is a noncompetitive inhibitor of viral reverse transcriptase. requires viral thymidine kinase for activity. 7 Cl Cl is used systemically. C 2 CC 2 C 2 Cl induces CYP 450 enzymes, which can lower serum levels of other drugs. inhibits 14α-demethylase in the biosynthesis of ergosterol. 23. The drug illustrated below is: is metabolically transformed into an inhibitor of dihydrofolate reductase. is commonly associated with hemolytic anemia inhibits the uncoating of influenza A 24. The combination drug listed b elow contains: Atripla Efavirenz Abacavir Lamivudine

8 25. The drug illustrated below: 8 binds to the D-ala-D-ala terminus of peptidoglycans in bacteria, blocking access by transferases. inhibits bacterial cell wall synthesis. is highly nephrotoxic when administered orally. 26. The drug illustrated below: cannot be administered orally. is always administered with ritonavir. acts as a transition state enzyme inhibitor. 27. The drug illustrated below: is converted to a mimic of guanosine. is used in combination therapy for the treatment of V infection. is used to treat hepatitis B.

9 28. The drug illustrated below: a P inhibits viral DA polymerase. C is administered only as a parenteral. can form chelates with various electrolytes. a a 9 3 C 29. The drug illustrated below: C 2 F can be administered orally or by intravenous injection. binds to the 23 ribosomal subunit of ribosomal RA. is used to treat vancomycin-resistant MRA infections. 30. The drug illustrated bel ow: is a V protease inhibitor. is a transition-state inhibitor. has multiple chiral centers. 31. The drug illustrated below: 2 C C 3 C 3 C 3 C is orally active. is not resistant to β-lactamase. has an extended spectrum of antibacterial activity that includes Gram (-) bacteria.

10 32. The drug illustrated below 2 2 C is used to treat hepatitis B infections. can be synergistic with Zidovudine (a thymidine mimic) in the treatment of V infection. causes viral DA chain termination. A nswer The drug illustrated below: 3 C 3 C 3 C C 3 C 2 C 3 C 3 3 C C 3 C 3 3 C C 3 C 3 C 3 C 3 is available as oral capsules as well as an iv formulation. is acid stable and need not be enteric coated for oral administration. inhibits CYP 3A4. C 3C 3C 34. The drug illustrated below: 35. The drug illustrated below: C3 3C is used to treat urinary tract infections. is used to treat conjunctivitis. is used to treat Crohn s disease. 2 is orally efficacious for treating fungal infections within the lumen of the G tract, but not orally efficacious for systemic fungal infections.. is often nephrotoxic upon prolonged parenteral administration. binds with cholesterol to increase the permeability of fungal cells.

11 36. The drug illustrated below: C 3 CCCC 3 C 3 can be administered orally. C 3 can cause severe hepatotoxicity. inhibits 14α-demethylase in the biosynthesis of ergosterol CC 3 C 37. The drug illustrated below: 2 is only administered intravenously. is typically used as monotherapy for early stages of tuberculosis infection. its active form is as the acid resulting from hydrolysis of the carboxamide. 38. The drug illustrated below is: C 3 C 3 C 3 C 3 3 C C 3 C 3 C The drug illustrated below: binds to 30 subunit of ribosomes and blocks protein synthesis. known to induce cytochrome P450 enzymes, such as CYP450 3A4. is used to treat tuberculosis. 2 2 C is used in combination with nucleoside reverse transcriptase inhibitors that mimic thymidine or 2 -deoxycytosine. is metabolically converted to a mimic of 2 -deoxyguanosine. requires activation by viral thymidine kinase.

12 40. The drug illustrated below: 12 is a prophylactic agent used to prevent the uncoating of influenza A. is orally active. binds to the receptor that V uses to bind and gain entry (CCR5) to human T cells. 41. The drug listed below: Enfuvirtide binds to gp41, a viral transmembrane protein of V-1, preventing cellular infection. is a 36 amino acid peptide. is administered by subcutaneous injection. 42. The drug illustrated below: 2 C C C C 3 C a a has β-lactamase resistance. is used against Gram (-) bacteria. orally efficacious. 3 C 43. The drug illustrated below: F C 3 C 2 causes double-strand DA strand breaks in bacteria. should not be taken with antacids, milk, or iron supplements. is associated with an increased risk of tendinitis and tendon rupture.

13 44. The drug illustrated below: 13 C 3 is used orally to treat hepatitis B. is a mimic of thymidine. is activated by conversion to its triphosphate. 45. The drug illustrated below: C 3 (C 3 ) 2 2 is commonly administered by intramuscular injection. can be administered intravenously. can cause phototoxicity (photosensitization) as a side effect. 46. The drug illustrated below is: is a fourth generation fluoroquinolone antibiotic. is indicated for treptococcus pneumoniae infection. is only effective against Gram (-) bacteria. 47. The drug illustrated below: 2 Cl 2 C C C 2 C 2 C 2 C 2 is formulated for intravenous administration. binds to the 50 ribosomal subunit of bacterial ribosomes. can produce aplastic anemia as an adverse side effect.

14 48. The drug illustrated below: 14 C 3 C C C 2 5 is used as a antiretroviral agent. is effective orally. is a neuraminidase inhibitor. 49.The drug illustrated below: is used to treat hepatitis B. could be cross allergenic in individuals allergic to sulfonamide antibiotics. is a prodrug The drug illustrated below: C 3 C C C is among the more effective cephalosporins against Gram (-) bacteria. is β-lactamase resistant. can be administered orally.

15 15 Part 2 Generic ames (9 Points). Provide the Generic ames for the Compounds listed on the following page. n the space provided under the structure of each the compounds illustrated, write the correct CAPTALZED letter corresponding to the choice of answers given on the following page. The letter Z may be used as an answer as seldom or as often as needed. C 2 5 F C 3 C 2 Cl C C 3 C 3 C 2 C 3 C 2 C 2 Cl C C CF 3 C 2 C 2 C 3 C C 2 3 CC 2 C C 3 CC 2 C C C 2 C C 3 C 2 (C 3 ) C 2 P() 2 C 3 C 3 Cl Cl 3 C C 3 C 3 C a C 3

16 A. Ceftibuten J. Minocycline. Ertapenem B. treptomycin K. Famciclovir T. Rifabutin C. Didanosine L. Amoxicillin U. aftifine D. Zanamivir M. tavudine V. Ciprofloxacin E. Pyrimethamine. traconazole W. Ethambutol F. Efavirenz. Darunavir X. Aztreonam G. Erythromycin P. Entecavir Y. Moxifloxacin. Cidofovir Q. Ribavirin Z. one of These. ulfadoxine R. afcillin 16 Part 3. omenclature 16 Points. 1) 1-Azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[(aminophenylacetyl)amino]-3-chloro-8-oxo- 2) 5-Amino-1-cyclopropyl-7-(3,5-dimethylpiperazin-1-yl)-6,8- difluoro-4-oxo-1,4-dihydroquinoline- 3-carboxylic acid, 7(3R,5)- 3) 1,3-Propanediol, 2-[2-(2-amino-8-chloro-9-purin-9-yl)ethyl]-

17 4) 3-soquinolinecarboxamide, decahydro-2,2-dimethyl-4-(phenylthio)butyl]-, [3R-[3α,4aβ,8aβ]]- 17 Exam Total: Part 1. Multiple Choice 75 Points Part 2. Generic ames 9 Points Part 3 omenclature 16 Points Total