What are functional analogues
Different chemical structure but similar pharmacological activity
What are the 3 classes of CCB
1,4-dihydropyridines
Benzothiazepine
Phenylalkylamine
What is the benzothiazepine drug
Diltiazem
What is the phenylalkylamine drug
Verapamil
What is a direct vasodilator and what is it’s MOA
Hydralazine
Inhibits inositol triphosphate induced release of calcium from SMC —> vasodilation
SAR of CCB 1,4-DHP
- Ester groups at position 3 and 5
- 1,4-DHP is essential
- Edg/ewg on phenyl ring at position 4 has to be in meta / ortho position
- Phenyl ring at position 4
- except for amlodipine all the CCB have 2,6-dimethyl groups
Which CCB is not a racemic mixture
Nifedipine
Is the s or r stereoisomers of verapamil and phenylalkylamines more potent
S
what is an adverse effect shared by all CCB
peripheral odema
common structural features of ARB (sartan)
tetrazole group
biphenyl ring
SAR of ARB
- acidic group –> Phe 8
- n-butyl group –> Ile 5
- imidazole –> His 6
the acidic group needs to be on ortho position of biphenyl ring
SAR of ACEI
- N ring contain COOH
- Zn binding groups (SH, COOH or POOH)
- esterification of COOH/POOh groups leads to better F
what are the 1st,2nd and 3rd gen of zn binding groups in ACEI
1st : sh
2nd : cooh
3rd : pooh
are 1,4-DHP or non-DHP more basic
non-DHP
why are non-DHP more basic
lone pair on N atom of 1,4-DHP delocalise into keto group –> less available for protonation –> less basic –> less ionised at physiological pH
CCB has a ___ log p
high
what is the lead compound of ACEi
teprotide
ace is a ____ enzyme
zinc metalloenzyme
which molecule has a similar enzymatic activity to ace
carboxypeptidase A
ARB prefer to bind to ___ recepors
at1
aliskiren may lead to
angioedema and diarrhoea
