MedChem - Proteases

ACe

Angiotensin converting enzyme: metallo-proteases, found in lung capillaries and kidneys tubules. Catalyses the conversion of Angiotensin I to Angiotensin II

ACE inhibition effects

• Reduction of blood Angiotensin II levels

• Reductions of plasma and urin Aldosterone levels

• Reduction of plasma noradrenaline levels

• Reduction of plasma and urine vasopressin

• Increase of plasma renin levels

• Increase of Bradykinin levels

Classes of ACE inhibitors

• Thiol

• Carboxylic

• Phosphinic

• Phosphonic

Differs by efficacy, ACE inhibition power, pharmacokinetics (intestinal absorption, half life, distribution etc…)

Thiol derivatives ACE inhibitors

Captopril.

Thiol is a better chelatant than carboxylic acid. But dimerizes in inactive derivatives, causing a short half life

Carboxylic derivatives ACE inhibitors

Enalapril → Enalapriat

Administered as prodrug (esters) to increase their low oral bioavailability.

Phosphinic & phosphonic derivatives ACE inhibitiors

Phosinoprilat & Ceronapril

Renin

Aspartic protease secreted by the kidney when blood pressure diminishes. Converts angiotensinogen (secreted by the liver) into angiotensin I

Renin inhibitors

Peptidic bond is mimicked by a non-hydrolyzable vicinal diol.

Remikiren, ciprokiren & aliskiren