C5 The chemical basis of drug action 2

Question 1

what class of drug / molecule is histamine?

Answer 1

an agonist

Question 2

what class of drug / molecule is cimetidine?

Answer 2

the first histamine 2 receptor antagonist

Question 3

where do histamine and cimetidine bind?

Answer 3

bind to the same location but cimetidine blocks the activity of the histamine agonist

Question 4

what are heteorcycles?

Answer 4

• rings that contain carbon atoms and other non-carbon atoms
• non-carbon atoms are called heteroatoms (eg. N, O and / or S)

Question 5

what is the importance of heterocycles?

Answer 5

‘in the pharmaceutical industry, over 75% of the top 200 brand name drugs incorporate heterocyclic motifs in their structures’

Question 6

name this heterocyclic system

Answer 6

pyrrole

Question 7

name this heterocyclic system

Answer 7

imidazole

Question 8

name this heterocyclic system

Answer 8

pyrazole

Question 9

name this heterocyclic system

Answer 9

furan

Question 10

name this heterocyclic system

Answer 10

thiophene

Question 11

name this heterocyclic system

Answer 11

oxazole

Question 12

name this heterocyclic system

Answer 12

thiazole

Question 13

what does the ending -azole indicate in the names of heterocyclic systems?

Answer 13

nitrogen in the ring as well as another heteroatom (could be another nitrogen)

Question 14

name this molecule

Answer 14

piperidine

Question 15

name this molecule

Answer 15

pyridine

Question 16

name this molecule

Answer 16

pyrimidine

Question 17

name this molecule

Answer 17

indole

Question 18

name this molecule

Answer 18

benzimidazole

Question 19

name this molecule

Answer 19

purine (imidazopyrimidine)

Question 20

where is pyrimidine seen a lot?

Answer 20

in nucleic acid bases

Question 21

name this sulfur-containing functional group

Answer 21

thiol

Question 22

name this sulfur-containing functional group

Answer 22

thioether

Question 23

name this sulfur-containing functional group

Answer 23

disulfide

Question 24

name this sulfur-containing functional group

Answer 24

sulfoxide

Question 25

name this sulfur-containing functional group

Answer 25

sulfone

Question 26

name this sulfur-containing functional group

Answer 26

sulfonamide

Question 27

what is sulfonamide seen a lot in?

Answer 27

antibiotics

Question 28

what does histamine stimulate and how?

Answer 28

- stimulates the secretion of acid by the parietal cells - interacts with H2-receptors in the parietal cells

Question 30

is an amine group electron-donating or electron-withdrawing? explain

Answer 30

- electron-withdrawing - pulls electrons out of the ring to make them less available (ring is less basic compared to imidazole on its own) - electrons are less available to take a proton because ring pulls the electrons from the side chain amine towards the ring so less basic than straight chain amine

Question 31

discuss basicity with different hybridisations

Answer 31

- sp2 hybridised is less basic because the electrons are less available - sp3 hybridised will be more basic

Question 32

when thinking about basicity, what must be considered?

Answer 32

hybridisation and inductive effects

Question 33

for bases, what percent of molecules will be ionised when the pH is 2 pH units below the pKa?

Answer 33

99% of the molecules will be ionised / protonated (rule of thumb)

Question 34

cimetidine, ranitidine, famotidine and nizatidine are all histamine-2 receptor antagonists. describe the common structure. describe the effects of the imidazole, furan and thiazole rings

Answer 34

- all have 5-membered heterocyclic ring, sulfur group and amine groups (except famotidine) - imidazole ring responsible for adverse drug reactions - furan or thiazole ring with a ring substituent that is a base increases selectivity and potency of antagonism at H2 receptors and reduces interactions with cytochrome P450

Question 35

are these H2 receptor antagonists basic or acidic?: cimetidine, ranitidine, famotidine and nizatidine

Answer 35

- cimetidine: weakly basic - ranitidine: weakly basic - famotidine: amphoteric - nizatidine: weakly basic

Question 36

what factor is important for binding to a receptor?

Answer 36

- ionisation - must be considered