antihypertensives medchem- calcium channel blockers

how do calcium channel blockers work

• they dont block the channel physically

• they target proteins that result in a conformational change in turn blocking channels

do calcium channel blockers block at different proteins

• no

• they block at the same protein just a different sites

what are the different examples of calcium channel blockers

• 1,4-dihydropyridines

• phenylalkylamines

• benzothiazepenes

• diaminopropanol

what are 1,4-dihydropyridines effective for and when do they work 

• effective for hypertension

• work when channel is open 

what are phenylalkylamines used for

for cardiac arrhythmias

what do diaminopropanols work on

Na+ channels

why did scientists think different calcium channel blockers worked on different chains

due to the lack of clear structural relationship between different calcium channel blockers 

why is the hantzch synthesis used for 1,4-dihydropyridines

• makes symmetrical substrates

• reliable 

what should we see on a 1,4-dihydropyridine structurally to increase activity of it being a blocker

• NH at top of aromatic ring- needs to be unsubstituted due to its key binding interactions 

• all have a 2,6 methyl substitution excluding amlodipine 

• esters on the 3,5 carbons- usually symmetrical but dont have to be 

• aromatic ring- they’re the best

• ortho/meta- EWG/EDG- on the aromatic increases activity but doesnt matter what is on those positions 

why shouldn’t you have an NO2 group on carbon 3 of a 1,4-dipyridine 

causes the channels to continuously be open 

why is there an alternative synthesis for 1,4-dipyridines 

• much cleaner synthesis

• ammonia is stinky and messy 

what are the 2 different types of allosteric relationships

• negative allosteric relationship

• positive allosteric relationship 

what happens in the negative allosteric relationship 

one substrate binds and the there doesnt 

what happens in the positive allosteric relationship 

• if one binds the other also binds 

• can improve the effective ness of each other

• but can also inhibit interactions