Moexipril

Originator

Moexipril,Schwarz Pharma,Germany

Uses

Antihypertensive; enzyme inhibitor (angiotensinconverting).

Definition

ChEBI: Moexipril is a peptide.

Manufacturing Process

1) A solution of 2.0 g of t-butyl alanine (S-form) and 3.78 g of ethyl 2-bromo- 4-phenylbutanoate in 25 ml of DMF was treated with 1.8 ml of triethylamine and the solution was heated at 70°C for 18 hours. The solvent was removed at reduced pressure and the residue was mixed with water and extracted with ethyl ether. The organic layer was washed with water and dried over magnesium sulfate. Concentration of the solvent at reduced pressure gave the oily ethyl-α-[(1-carboxyethyl)amino]benzene-t-butanoate.
A solution of 143.7 g of this t-butyl ester in 630 ml of trifluoroacetic acid was stirred at room temperature for one hour. The solvent was removed at reduced pressure and the residue was dissolved in ethyl ether and again evaporated. This operation was repeated. Then the ether solution was treated dropwise with a solution of hydrogen chloride gas in ethyl ether until precipitation ceased. The solid, collected by filtration, was a mixture of diastereoisomers of ethyl-α-[(1-carboxyethyl)amino]benzenebutanoate hydrochloride, melting point 153-165°C; [α]D23 = +3.6° (1% MeOH).
The free amino acid (S,S-form) was prepared by treatment of an aqueous solution of the hydrochloride with saturated sodium acetate. The product was filtered, washed efficiently with cold water and recrystallized from ethyl acetate; melting point 149-151°C; [α]D23 = +29.7°.
2) A stirred solution of 0.0158 mole of ethyl-α-[(1-carboxyethyl)amino] benzenebutanoate hydrochloride in 200 ml of methylene chloride was treated successively with 1.60 g (0.0158 mole) of triethylamine, 0.0158 mole of 1- hydroxybenzotriazole, 0.0158 mole of 1,2,3,4-tetrahydro-6,7-dimethoxy-3- isoquinolinecarboxylic acid and then with 0.0158 mole of dicyclohexylcarbodiimide in 10 ml of methylene dichloride. Dicyclohexylurea gradually separated. The mixture was allowed to stand at room temperature overnight. Hexane (300 ml) was added and the urea was filtered. The filtrate was washed with 250 ml of saturated sodium bicarbonate, dried over sodium sulfate and concentrated to remove solvent. The viscous residue was triturated with 50 ml of ether and filtered to remove insolubles. The filtrate was concentrated to give 2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1- oxopropyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid.
After addition of hydrochloric acid was obtained 2-[2-[[1-(ethoxycarbonyl)-3- phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-6,7-dimethoxy-3- isoquinolinecarboxylic acid, hydrochloride.

brand name

Univasc (Schwarz Pharma).

Therapeutic Function

Antihypertensive