Medicinal Chemistry I Examination Name December 15, 2009 Med. Chem. #

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1 Medicinal Chemistry Examination ame December 15, 2009 Med. Chem. # Part. 80 Points (40 Questions; 2 Points Each) Select the BEST answer for each of the following. f none of the answers are correct, do not fill in the Scantron for that particular question and write E on your exam. 1. Which of the comments are valid- Low-molecular weight heparins (LMWs) cannot be administered orally. can be used to prevent deep vein thrombosis. are associated with a lower risk for heparin-induced thrombocytopenia syndrome (T syndrome). 2. The drug illustrated below has: C 3 C 2C 2 C 3 sedative effects. antipruritic activity. antiemetic activity. 3. The drug illustrated below: 3 C S is not available as a tablet. stabilizes mast cells, reducing the exposure to histamine. is a non-competitive 1 -receptor antagonist. 1

2 4. The drug illustrated below: can stimulate appetite and can cause weight gain. is available TC. is non-sedating 1 -receptor antagonist. C 3 C 2 C 5. The drug illustrated below: C 3 C S inhibits the ADP binding to receptors on platelets by causing an reversible modification. reduces platelets by limiting the maturation of megakaryocytes into platelets. is administered orally. 6. The drug illustrated below: C 2 R R 2 C R R R R R R is approved for the treatment of duodenal ulcers. is effective in lowering stomach p. can be used in individuals with chronic renal failure. R = S 3 [(Al) 2 ()x( 20 )y] 2

3 7. The drug illustrated below: C 2 C 2 C 2 C 2 C C 2 C 3 frequently causes heparin-induced thrombocytopenia (T). S has the same mechanism of action as heparin. is a direct thrombin inhibitor. C 3 8. The drug illustrated below: S 2 is the most potent of the 2 -rceptor antagonists. C 2 causes an increase in gastric p. C 2 S C 2 C 2 inhibits hepatic enzymes. 2 C 2 S 9. The drug illustrated below is: Lepirudin. is used to inactivate heparin. is a glycoprotein. is a direct thrombin inhibitor that is cleared via the kidneys. 10. The drug illustrated below: binds to antithrombin eparin accelerates the inactivation of several clotting factors. activates prothrombin. 3

4 11. The drug illustrated below: C C S C 2 C 2 C 2 C 2 C 3 2 binds to GPB/A receptors blocking access by fibrinogen. accelerates the degradation of fibrin clots. unlike eptifibatide, is administered orally. 12. The drug illustrated below: C C 2 C C 2 C 2 C3 C The drug illustrated below is: is an antidepressant. can be administered topically to the eye. is used to treat allergic conjunctivitis. a 1 -receptor agonist. among the less sedating of the first-generation antihistamines. available TC. 14. Which of the comments are valid: is a serine protease. Urokinase.. is isolated from human kidney tissue cultures. is an enzyme inhibitor. 4

5 15. The drug illustrated below: a C 2 S C 2 C 2 C 2 C 3 C 3 is metabolically-transformed to an electrophile is manufactured as an enteric-coated tablet. is used not ony for the treatment of duodenal ulcers, but also gastroesophageal reflux disease, GERD. 16. The drug illustrated below: C 2 activates antithrombin inhibits Vitamin K epoxide reductase. inhibits the synthesis of Factor X, the Stuart-Prower factor. C The drug illustrated below: C 2 C 2 C 2 C 3 C C C 3 C C is selective for peripheral 1 -receptors. is a h-erg channel inhibitor. is used to prevent motion sickness. 5

6 18. The drug illustrated below is: C 2 C 3 an antihistamine that is administered as a nasal spray. is used topically as an opthalmic. is non-sedating. 19. The drug illustrated below: C 2 CC 3 irreversibly inhibits cyclooxygenase in platelets. inhibits the formation of thromoxane A 2 (TXA 2 ) in platelets. can limit mucus formation associated with the lining of the stomach. 20. The drug illustrated below: C 2 C 2 C 2 C 2 blocks ADP receptors.. inhibits platelet aggregation.. specifically inhibits posphodiesterase type 3 (PDE 3) 6

7 21. The drug illustrated below C 3. is a prodrug of caffeine. 3 C C 3 A. B. only only is weakly basic. is used to treat infant apnea. 22. The drug illustrated below 23. is extensively metabolized. 24. is metabolized through oxidative reactions. 25. is resistant to hydrolysis. A. B. only only 23. The drug illustrated below. is weakly acidic. is not metabolized through oxidative phase reactions. is used to treat neurological conditions characterized by excessive daytime sleepiness. A. B. only only 7

8 24. The drug illustrated below. is used as an appetite suppressant. is just as likely to lead to abuse as amphetamine. has one chiral center and thus two stereoisomers with the S-enantiomer being more active. 25. The drug illustrated below. is used along with diet and exercise for the short-term treatment of obesity. is metabolized through oxidative -demethylation. has two chiral centers and four stereoisomers. 26. The drug illustrated below. is used as an anorexient. has a phenyl ring with reduced metabolic liability. is metabolized through -demethylation to give two inactive amine metabolites. 8

9 27. The drug illustrated below. reversibly inhibits pancreatic lipase. is synthetic analog of natural product called lipstatin. contains a lactone functional group. 28. The two structures illustrated below. are enantiomers. are both erythro isomers. A is the more active isomer marketed as dexmethylphenidate for ADD. 29. The drug illustrated below 2. contains amino acid leucine. is a prodrug used for ADD in 6-12-year-olds. 2 is metabolized to release the active drug through hydrolysis. 9

10 30. The drug illustrated below. is an SSR used as an antidepressant. is mainly metabolized through reductive pathways. is orally active. 31. The drug illustrated below. is a mechanism-based MA inhibitor used to treat depression. is a reversible inhibitor. has one chiral center and thus two stereoisomers. 32. The drug illustrated below. is an antidepressant that can be used to treat enuresis. is metabolized through aromatic hydroxylation followed by conjugation reactions to inactive metabolites. is metabolized to secondary and primary amine metabolites that are inactive. 10

11 33. The drug illustrated below. is used for the relief of symptoms of depression. has antipsychotic properties due to its D 2 receptor blocking activity. Chlorine substitution makes the benzene ring on the right more susceptible to metabolic hydroxylation. 34. The drug illustrated below. is a strong 1 antagonist leading to sedative side effects. is an antagonist leading to increased adrenergic and serotonergic transmission. is an agonist at 5-T 2A, 5-T 2C, and 5-T The drug illustrated below CF 3. induces enzymes responsible for its own metabolism leading to a shorter half life after long-term use. is extensively metabolized through demethylation resulting in an active metabolite. is an SSR that can be used to treat alcoholism. 11

12 36. The drug illustrated below. is an SSR that can be used to treat CD. is extensively metabolized to hydroxyl-containing metabolites and their conjugates. is orally inactive and has to be administered through injection. 37. The drug illustrated below. has a metabolite with the t-butyl group removed through oxidative dealkylation. is metabolically reduced to a primary alcohol. is used for smoking cessation. 38. The drug illustrated below. can be viewed as a conformationally restricted analog of sumatriptan. has a short half life just like most other triptans. is a 5-T 1 receptor antagonist indicated for migraine headache. 12

13 39. The drug illustrated below. is a 5-T 1 receptor agonist. is effective against vomiting and nausea. has a pharmacophore consisted of a basic center and an aromatic ring linked through a carbonylcontaining linker. 40. The drug illustrated below. is used for the prevention of nausea and vomiting in combination with other antiemetics.. is a substance P antagonist on K1 receptor. The F and CF 3 help deactivate the aromatic rings and increase metabolic stability. Part * Points (4 Questions, 1 Point each) 51. and 52. Match a structure provided below to the generic name A B C CC 2 C 2 C 3 C 3 D C 3 C 2 C 2 C 2 E 51. Desipramine 13

14 52. Match a structure provided below to the generic name F 3 C C 3 A B C C 3 S D C 3 E 52 Sertraline 53. Match a structure provided below to the generic name S S 2 A B C C 3 C 2 C D E S 53. Eptifibatide 14

15 54. Match a structure provided below to the generic name C 2 A B C C 2 C 2 C 2 C 2 C 3 C 2 C 2 C 2 C 3 C 3 D E 54. Emedastine Part (16 Points) Complete the structures of the FUR following compounds Draw the correct chemical structure, including stereochemistry wherever indicated. Partial credit will be given but you will lose points for incorrect chemical symbols, hydrogens missing from heteroatoms, hydrogens missing from carbons labeled C, and for having too many bonds to an atom (see below for examples). Examples: ncorrect chemical symbol (-1 point each) ydrogen missing from nitrogen (-1 point) Fl n 5 bonds to carbon (- 2 points) ncorrect: Fluorobenzene Piperidine C C C ydrogens missing from carbon chain (-1 point Correct: F or C 2 C 2 C Piperazineacetamide, -(2-methyl-4-(imidazol-1-yl)phenyl)-4-[2-hydroxy-3- (2-ethoxyphenoxy)propyl]- dihydrochloride 15

16 2. Piperidine, 4-(11-dibenzo[b,e]azaepin-11-ylidene)-1-benzyl-, hydrochloride 3. (R)-3-(Dimethylamino)--(cyclopropyl)-2,3,4,9-tetrahydro-1-carbazol-6- methylsulfonamide 4. Ethanamine, 2-[(4-chlorophenyl)-2-pyridinylmethoxy]--phenyl--(2-pyridyl) There are Twelve pages in this exam! Part Part Part 80 points 4 points 16 points 16