Description
Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor (IC
50 = 1.2 nM). It reduces the formation of endothelin-1 and increases nitric oxide (NO) in human vascular endothelial cells when used at a concentration of 0.1 nM. Lisinopril inhibits the pressor response to angiotensin I in anesthetized rats and dogs (ID
50s = 2.3 and 6.5 μg/kg, respectively).
Originator
Acebitor 5,Biddle Sawyer,India
Uses
Labeled Lisinopril, intended for use as an internal standard for the quantification fo Lisinopril by GC- or LC-mass spectrometry.
Uses
Lisinopril is an antihypertensive medication.
Definition
ChEBI: Lisinopril is a dipeptide. It has a role as an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor. It contains a L-prolino group and a L-lysine residue.
Manufacturing Process
2-Oxo-4-phenylbutyric acid and t-BOC-L-lysyl-L-proline are condensed in the
presence of sodium cyanoborohydride. Essentially all of the t-BOC protecting
group is cleaved when the product is absorbed on strong acid ion exchange
resin. The crude N-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline is eluted from
the resin with 10% ammonia, freeze dried, and purified by gel filtration
chromatography (LH-20). A minute peak for t-BOC protons in the NMR
spectrum disappears when the product is treated with ethyl acetate that is 4
N in hydrogen chloride gas. The NMR spectrum of the resulting HCl salt of the
product is consistent with structure. The mass spectrum shows a molecular
ion at 693 m/e for the tetrasilylated species. Chromatography on XAD-2 resin
using 3.5% acetonitrile in 0.1 molar ammonium hydroxide affords N-α-((1S)-
1-carboxy-3-phenylpropyl)-L-lysyl-L-proline. The last peptide can be produced
if 2-oxo-4-phenylbutyric acid and N-t-Boc-L-lysyl-L-proline are condensed in
the presence of sodium cyanoborohydride. The product is absorbed on strong
acid ion exchange resin, and eluted with 2% pyridine in water. Product-rich
cuts are stripped to a glass and treated with 4 N HCl in ethylacetate to
remove the t-Boc protecting group. The resulting hydrochloride salt is
converted to the free base by absorbing on strong acid ion exchange resin and
eluting with 2% pyridine in water. Freeze drying of product-rich cuts affords
N-α-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline as a white fluffy solid. The
NMR spectrum is consistent with structure. The mass spectrum shows a
molecular ion at 549 for the disilylated species. Chromatography affords the
desired isomer.
brand name
Prinivil (Merck); Zestril (AstraZeneca).
Therapeutic Function
Antihypertensive
