1. 11/9/2010
ACE INHIBITORS,
ANTAGONISTS &
BLOCKERS
Malina Jasamai
Faculty of Pharmacy, UKM
malina@pharmacy.ukm.my
 Blood pressure regulation by renin-
angiotensin system
- ACE
- angiotensin II receptors
- renin
 Regulation of aldosterone secretion
BACKGROUND KNOWLEDGE
 Predicts metabolites produced by ACE
inhibitors and angiotensin anatagonists
 Relates modification of functional groups
with potency of ACE inhibitors and
angiotensin anatagonists
LEARNING OUTCOMES
1

2. 11/9/2010
 Wilson & Gisvold’s textbook of organic
Medicinal & pharmaceutical chemistry,
12th ed. Beale Jr., J.M. & Block, J.H.,
Lippincott Williams & Wilkins
REFERENCES
anthropology.net/2007/07/30/find...yme-ace/
ACE INHIBITORS
Active site presumed to be the arginine
residue
- provide cationic site which attract
carboxylate & zinc ions
 Side effects of rash & loss sense of taste
with thiol containing compound
ACE INHIBITORS
2

3. 11/9/2010
O O
HO
HO O O
OH
O N
N
H O
Benzylsuccinic acid Ramipril
O O
HS O
O
N
N N
OH H O OH
O
Captopril Enalapril
ACE INHIBITORS
 Losartan
- nonpeptide drug
- parent drug & metabolite both has high
affinity fot T1.
- acidic tetrazole involves in binding
- biphenyl separates tetrazole from
aliphatic N
ANGIOTENSIN ANTAGONISTS
 Ibersartan
- doesn’t possess acidic side chain
 Valsartan
- COOH chain in valine moiety
ANGIOTENSIN ANTAGONISTS
3

4. 11/9/2010
OH
Cl O
N N N
N NH N NH N
N N N N
Losartan Ibersartan
OH
N O
N NH
N N
O
Valsartan
ANGIOTENSIN ANTAGONISTS
4