Birla Institute of Technology & Science-Pilani, Hyderabad

BIRLA INSTITUTE OF TECHNOLOGY & SCIENCE-PILANI, HYDERABAD CAMPUS I SEMESTER 2010-2011 PHA C342: MEDICINAL CHEMISTRY COMPREHENSIVE EXAMINATION PART-A (CLOSED BOOK) Date: 9 th May 2011 Weightage: 10% Duration: 60 mins Max. Marks: 30

1. Choose an appropriate answer from the choice given in each of the following questions. (5) a. Replacement of the oxygen at C-2 of barbituric acid by a sulphur atom i. Has no change on activity ii. Increases activity iii. Decreases activity iv. Shows anxiolytic activity b. One of the following is false about benzodiazepines: i. Alkyl substitutents at 3-position decreases the activity ii. The N-substitutent at 1-position should be small iii. A phenyl or pyridyl at the 5-position decreases activity

iv. The presence of electron-attracting substituents (Cl, F, Br, NO 2) at position 7 is required for activity. c. One of the following is an ester: i. Morphine ii. Phenazocin iii. Heroin iv. Ketobemidone d. Side-effects of NSAIDs include the following except i. Peptic ulcer ii. Reduced kidney function iii. GIT bleeding iv. Seizures e. The antihistamine drug with no heteroaryl ring system in its structure is i. Doxylamine ii. Triprolidine iii. Medrylamine iv. Meclizine 2. Give an example for each of the following with brief information: (2 x 5 = 10 ) a. Discovery of drugs through natural sources b. Accidental drug discovery c. COX-2 specific drugs d. Drugs fro insomnia with a short duration of action e. Drug based on acetanilide template 3. Give the mechanism of action of the following in brief: (2 x 5= 10 ) a. Lamivudine; b. Carmustine; c. Alprazolam; d. Benoxinate; e. Celecoxib 4. Complete the synthesis giving the intermediate products ( 5)

NH2 HNO 3 / H 2SO 4 H2N CH 2COOC 2H5 A B O + P2S5

H3C OC 2H5 N HC NH 2CH 2COOH C H C OC 2H5 3 D DCC Dimethyl formamide (activator for COOH) diethyl acetal E

HC N N CH3 O N N

N O2N

Cl BIRLA INSTITUTE OF TECHNOLOGY & SCIENCE-PILANI, HYDERABAD CAMPUS I SEMESTER 2010-2011 PHA C342: MEDICINAL CHEMISTRY COMPREHENSIVE EXAMINATION PART-B (OPEN BOOK) Date: 9 th May 2011 Weightage: 25% Duration: 120 mins Max. Marks: 50

1. Give the synthetic protocol for the following: (5 X 2 = 10 ) a. b. H NO S H2NO2S 2 2 C H 2 5

CH3

Cl N

O N O

CH3

N H

2. For the given structural template of a candidate drug, answer the following, (6)

a. What is the template’s basic biological activity expected? b. Does this template give an idea of a candidate drug’s ability to cross the Blood Brain Barrier? c. If n=2, what kind of activity can be exhibited by the candidate drug? Give an example and explain d. If n=3, what kind of activity/toxicity can be exhibited by the candidate drug? Give an example and explain e. What could be role of the aryl function in this template? f. What could be the role of the terminal tertiary amino function? If it is secondary or primary nitrogen does it make a difference to this role?

3. Complete the following reaction by giving suitable structures: (10 )

a. 6-Chloro-5-nitropyrimidin-4-amine I II

III

b. 5-(Hydroxymethyl)dihydrofuran-2(3H)-one IV

V VI VII

Bu4NF VIII IX X 4. Identify the name of the drug (1 mark) based on the information given below and give structure (1 mark) and mechanism of action (1 mark) for each. ( 3 x 5 = 15) a. The starting material for the synthesis of this drug is tetrafluorobenzoic acid. An oily residue which is sterospecific is obtained at 0 °C. b. The starting material for the synthesis of this drug is 3,4- dimethoxyphenylacetonitirle. The alkylating agent used is N-[2-(3,4- dimethoxyphenyl)-ethyl]-N-3-(chlorophenyl-N-methylamine. c. This drug is a racemate. It contains a tricoordinated sulphur atom in a pyramidal structure and therfore, can exist in equal amounts of both S and R enantiomers. In the acidic conditions of the stomach, both are converted to achiral products. d. This drug is obtained by bis-alkylating 2-aminopyridine with 2- dimethylaminoethylchloride and followed by 4-methoxybenzylchloride. e. The drug synthesis involves two famous reaction, i.e. Knoevenagel and Bischler- Napieralski reactions. 5. Give the synthetic scheme for the following: ( 3 x 3=9 ) a. 1-(ter -Butlyamino)-3-[(4-piperazino-1,2,5-thiadiazol-3yl)oxy]-2-propanol b. 4-Phenyl-1-(4-hydroxyphenyl)-2-(4-chlorophenyl)pyrazolidine-3,5-dione c. N-[3-(7-cyano-1,5,9-triazabicyclo[4.3.0]nona-2,4,6,8-tetraen-2yl)phenyl]-N- ethyl-acetamide _)_)_)_)_)_)_)_)_)_)_)_)_)_THE END_(_(_(_(_(_(_(_(_(_(_(_(_(_(_(_(_