MEDICINAL CHEMISTRY I EXAM #1

Transcription

1 MEDICIAL CEMISTRY I EXAM #1 1 September 28, 2007 ame SECTI A. Answer each question in this section by writing the letter corresponding to the best answer on the line provided (2 points each; 50 points total) 1. The compound shown below: I Is a cyclic urea II Is piperidine-2,5-dione III Is a cyclic imide 2. The compound illustrated below: C 3 I 3 C II III C 3 as cis-1,4-dimethyl groups as trans-1,2-dimethyl groups Is drawn in its lowest energy conformation 3. For the structures illustrated below: I Compound A has a larger pk a than 3 C C compound B II Compound A has a higher log P than compound B III The K a for Compound B is larger than the K a for Compound A

2 4. The compound illustrated below: I Is 1-Benzyl-4-benzoylisoquinoline II Is 1-Benzoyl-4-benzylisoquinoline III Is 4-Benzoylbenzo[a]isoquinoline 2 5. The compound illustrated below: I Is aromatic II as the lone pair of electrons (on the nitrogen), in the plane of the ring III Is non-aromatic 6. The compound shown below: 3 C I Is 2-2,7-dimethyl-5,6,7,10- tetrahydrooxecine C 3 II as two alkenes that have (E)- stereochemistry III Is antiaromatic

3 7. For the compounds illustrated below: C 3 C 3 I Compound A has four chiral centers II Compound A is a diastereomer of Compound B III Compound B is the enantiomer of Compound A 3 C C 3 3 C C The compound illustrated below: C 3 I Is 10-methylphenothiazine II as a conjugate acid with a pk a of 2 III Is 5-methylphenothiazine S 9. The compound illustrated below: I Is 50% ionized at p 12 II Is the conjugate base of 1,3,4,5-tetrahydro-2benzo[b]azepin-2-one III Is 100% ionized at p Consider the two structures shown below: F 3 C C 3 3 C C 3 I Compound A has a lower log P than Compound B II Compound B is a stronger base than Compound A III Compound A has a higher log P than Compound B

4 11. The compound shown below: I Contains an amine II Contains an imine III as a conjugate acid with a pk a = The compound illustrated below: I Is aromatic II Is a cation derived from 1,3,5-cycloheptatriene III Is 1-azepine 13. In the compound illustrated below: 3 C C 3 I The lone pair of electrons on the nitrogen is in a plane C C that is perpendicular to that which contains the two methyl 3 C groups attached to carbon. II The lone pair of electrons on the nitrogen is in the plane of the two methyl groups attached to carbon. III The carbon that is double bonded to both carbon and nitrogen has sp 2 hybridization 14. The compound illustrated below: C 3 C 3 I as an optical rotation of 0 2 C 2 4 C 2 2S,4S-2,4-dimethylpentane-1,5-diol II Is 2R,4R-2,4-dimethylpentane-1,5-diol III as the opposite optical rotation of

5 15. In the structure illustrated below: I The two carbonyl groups are in perpendicular planes II The spiro carbon (the carbon that is common to both rings) is sp hybridized III The two carbonyl groups are in the same plane The compound illustrated below: C I as 1S,4S stereochemistry II as a 3,4-dichlorophenyl substituent that is trans to a methylamino substituent III as 1R,4R stereochemistry 17. For the structures illustrated below: 2 I Compound A is a resonance structure of Compound B II Compound A is a tautomer of Compound B III Compounds A and B both have pk b values = For the two compounds illustrated below: I Compound B is a stronger base than compound A II Compound A is a stronger base than Compound B III Compound B has a conjugate acid with a pk a = 4

6 19. The compound illustrated below: C C C 3 Valine I II III Is D-Valine as S-stereochemistry Is L-Valine For the structures shown below: I Compound A is a weaker base than Compound B II Compound A is a stronger base than Compound B III The chlorine in Compound B stabilizes its conjugate acid form by resonance 21. In the compound illustrated below: I A is the Pro-R hydrogen II A and B are enantiotopic III B is the Pro-R hydrogen A B a) only 22. The structure shown below: I Is 2,7-Dimethyl-10-thioxanthene II Is 3,7-Dimethylphenothiazine 3 C S C 3 III Is 3,6-Dimethyl-9-thioxanthene

7 23. For the structures shown below: I Structure A is the anti- conformation of 1,2- dichloroethane II Structure B is the gauche conformation of 1,2- dichloroethane III Structure B is higher in energy than structure A The compound illustrated below: C 2 I Is 50% ionized at p 4 II Is 50% ionized at p 9 III Is 50% ionized at p For the compounds illustrated below: I Compound A has a pk b = 12 II Compound B has a pk b = 10 III The nitrogen of Compound A is sp 2 hybridized

8 SECTI B. 15 Points Total For the following pair of compounds assign the proper stereochemistry (R or S) at each chiral center in each molecule. Then indicate on the line the relationship of the compounds to each other by writing the word EATIMER, DIASTEREMER, R SAME CMPUD. (5 Points). 2 C C 2 C 2 Relationship 2. Assign the stereochemistry of the compound shown below by clearly writing the letter E- or Z- next to each assignable double bond, as appropriate. (2 Points). C C 2 3. The following compound is the sugar D-Idose. It has an optical rotation [ ] = Upon reaction with and SC 2 C 2 C 2 S the aldehyde group of D-Idose is converted into a dithioacetal and that compound hash a melting point of 141 C and an optical rotation [ ] = Indicate the absolute configuration at each chiral center of D-Idose (R or S). Then answer the questions below pertaining to Compound B. (8 Points). C C 2 C C 2 S S C 2 S S C 2 D-Idose Compound B D-Idose dithioacetal mp = 141 o C [ ] = o Dithioacetal of Compound B a) What is the relationship (enantiomer, diastereomer, or same compound) of Compound B to D-Idose? b) Would the optical rotation of Compound B be: +15.8, -15.8, +51.0, 0, or is there not enough information to determine it?

9 % of Maximal Response c) Explain your answer from question b). 9 d) If Compound B was allowed to react at its aldehyde group with and SC 2 C 2 C 2 S to form a dithioacetal would that compound have a melting point of: 141 C, -141 C, 0 C, or is there not enough information to determine what the melting point would be? SECTI C. For each of the following fill in the blank with the appropriate response. (5 Points). 1) Refer to the graph shown below and then write on the line provided which of the following statements is false? a) Drug A is less potent than Drug B b) Drug B has equal efficacy as Drug A c) Drug B is less potent than Drug A 100 A B 50 0 log dose 2) n the line provided write the letter of the phrase which BEST completes the following statement: The critical portion of the structure of a drug that binds to the receptor is called the a) hot spot b) pharmacophore c) active site. 3) n the line provided fill in the missing phrase. The four major steps in drug discovery are: a) Target identification and selection b) Target optimization c) Lead identification and d). 4) n the line provided write whether the following statement is True or False. A thiophene ring can be used as a bioisosteric replacement for a phenyl ring. 5) n the line provided write whether the following statement is True or False. The efficacy of a ew Chemical Entity (CE) is first evaluated during Phase II clinical trials.

10 10 SECTI D. For each of the following pairs of compounds circle the one that has the higher log P. (5 points). a) 3 C 3 C b) c) (C 3 ) 4 (C 3 ) 2 C 2 C 3 d) C 3 C 3 C 3 C 3 e) F F SECTI E. For each of the following systematic names, 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 as C, and for having too many bonds to an atom. (25 Points) [1,4]Diazepino[1,2-a]indole, 2,3,4,5-tetrahydro-, Monohydrochloride

11 11 2. (E)-4-[2-Chloro-4-(4-methoxyphenyl)but-3-en-1-yl]morpholine 3. Butyl 3-Phenyl-3-(1-piperidinyl)propionate, (S)-enantiomer 4. 2-Amino-6-ethyl-5,6,7,8-tetrahydro-4-oxazolo[4,5-d]azepine 5. (Z)-3-[8-Chloro-5-dibenzo[b,f]azepin-10(11)-ylidene]-,-dimethylpropanamine