HCI Prelim CHEM

HWA CHONG INSTITUTION This question booklet consists of 15 printed pages C2 PRELI MINARY EXAMINATION CHEMISTRY 9812 HIGHER 3: PHARMACEUTICAL CHEMISTRY 24 September 2009 2 h 30 min Do not open this booklet until you are told to do so. INSTRUCTIONS TO CANDIDATES 1) This paper consists of 15 printed pages (including this page). You should have a Data Booklet, a cover page and a set of writing papers. 2) Answer any five questions. 3) Write your name and CT clearly on the cover page and on all the work you hand in. 3) Begin each question on a FRESH sheet of writing paper. A nil return is necessary for any unattempted question. 4) At the end of the examination, fasten your cover page securely together with your answer scripts. INFORMATION FOR CANDIDATES The number of marks is given in brackets [ ] at the end of each question or part question. A Data Booklet is provided. You may use a calculator. You are reminded of the need for good English and clear presentation in your answers.

2 C2 Chemistry H3 Prelim 2009 9812/01/HCI 1 Analgesic drugs are a diverse group of compounds that are capable of relieving pain. They can be classified into two categories, the narcotic and non-narcotic analgesics. (a) Narcotic and non-narcotic analgesics act differently to prevent pain. Briefly describe the differences in their modes of action. [2] (b) State two sources for which potential drug candidates may be identified. [2] (c) Non-steroidal anti-inflammatory drugs (NSAIDs) belong to the class of non-narcotic analgesics. They include the following molecules: Cl CH3 CO2H CH3 H3C ibuprofen CO2H OCOCH3 aspirin N H3CO O CH3 CO2H indomethacin NSAIDs work by preventing arachidonic acid from binding to the active site of cyclooxygenase. CO2H CH3 arachidonic acid The active site of cyclooxygenase consists of the following amino acid residues: amino acid serine arginine tyrosine R-group –CH2OH NH CH2 OHNH2N H The different modes of action for NSAIDs involves: (1) covalent modification of the serine residue in cyclooxygenase (2) reversible inhibition at the substrate-binding site (3) competitive inhibition of cyclooxygenase via interactions with arginine and tyrosine (i) Assign the NSAIDs modes of action (1) – (3) to ibuprofen, aspirin and indomethacin and justify your answer. Each NSAID should only be used once. [4] (ii) SC−558 is also a type of NSAIDs. Copy the molecule onto your answer sheet and indicate on the diagram two different types of molecular interactions it can have with the amino acids at the cyclooxygenase active site. N NS O O H2N CF3 SC–558 [2]

3 C2 Chemistry H3 Prelim 2009 9812/01/HCI The ether group in indo methacin can be formed via a nucleophilic substitution reaction. (d) (i) Draw the precursor and state the reagents and conditions required