C5 The chemical basis of drug action 2 Flashcards
what class of drug / molecule is histamine?
an agonist
what class of drug / molecule is cimetidine?
the first histamine 2 receptor antagonist
where do histamine and cimetidine bind?
bind to the same location but cimetidine blocks the activity of the histamine agonist
what are heteorcycles?
- rings that contain carbon atoms and other non-carbon atoms
- non-carbon atoms are called heteroatoms (eg. N, O and / or S)
what is the importance of heterocycles?
‘in the pharmaceutical industry, over 75% of the top 200 brand name drugs incorporate heterocyclic motifs in their structures’
name this heterocyclic system
pyrrole
name this heterocyclic system
imidazole
name this heterocyclic system
pyrazole
name this heterocyclic system
furan
name this heterocyclic system
thiophene
name this heterocyclic system
oxazole
name this heterocyclic system
thiazole
what does the ending -azole indicate in the names of heterocyclic systems?
nitrogen in the ring as well as another heteroatom (could be another nitrogen)
name this molecule
piperidine
name this molecule
pyridine
name this molecule
pyrimidine
name this molecule
indole
name this molecule
benzimidazole
name this molecule
purine (imidazopyrimidine)
where is pyrimidine seen a lot?
in nucleic acid bases
name this sulfur-containing functional group
thiol
name this sulfur-containing functional group
thioether
name this sulfur-containing functional group
disulfide
name this sulfur-containing functional group
sulfoxide
name this sulfur-containing functional group
sulfone
name this sulfur-containing functional group
sulfonamide
what is sulfonamide seen a lot in?
antibiotics
what does histamine stimulate and how?
- stimulates the secretion of acid by the parietal cells
- interacts with H2-receptors in the parietal cells
is an amine group electron-donating or electron-withdrawing? explain
- 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
discuss basicity with different hybridisations
- sp2 hybridised is less basic because the electrons are less available
- sp3 hybridised will be more basic
when thinking about basicity, what must be considered?
hybridisation and inductive effects
for bases, what percent of molecules will be ionised when the pH is 2 pH units below the pKa?
99% of the molecules will be ionised / protonated (rule of thumb)
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
- 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
are these H2 receptor antagonists basic or acidic?: cimetidine, ranitidine, famotidine and nizatidine
- cimetidine: weakly basic
- ranitidine: weakly basic
- famotidine: amphoteric
- nizatidine: weakly basic
what factor is important for binding to a receptor?
- ionisation
- must be considered
