76420-72-9

Basic information

• Product Name: Enalaprilat
• Synonyms: ENALAPRILAT HYDRATE;ENALAPRILAT USP(CRM STANDARD);Enalaprilic Acid;N-[(1S)-1-(Carboxy)-3-phenylpropyl]-L-alanyl]-L-proline Dihydrate;Vasotec IV;(2S)-1-[(2S)-2-[[(1S)-1-Carboxy-3-phenyl-propyl]amino]propanoyl]pyrrolidine-2-carboxylic acid;Enalaprilat;Enalapril acid
• CAS NO: 76420-72-9
• Molecular Formula: C₁₈H₂₄N₂O₅
• Molecular Weight: 348.39
• EINECS: 278-459-3
• Product Categories: Active Pharmaceutical Ingredients;Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Metabolite
• Mol File: 76420-72-9.mol
• Article Data: 8

Chemical Properties

• Melting Point: 148-151°C
• Boiling Point: 601 °C at 760 mmHg
• Flash Point: 317.3 °C
• Appearance: white crystalline solid
• Density: 1.286±0.06 g/cm3(Predicted)
• Vapor Pressure: 2.71E-15mmHg at 25°C
• Storage Temp.: 2-8°C
• Solubility: Very slightly soluble or slightly soluble in water, sparingly soluble in methanol, practically insoluble in acetonitrile.
• PKA: pKa 2.30 (Uncertain);3.39 (Uncertain)
• Water Solubility: Soluble in water with heating (~60°C)
• CAS DataBase Reference: Enalaprilat(CAS DataBase Reference)
• NIST Chemistry Reference: Enalaprilat(76420-72-9)
• EPA Substance Registry System: Enalaprilat(76420-72-9)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 2
• Hazardous Substances Data: 76420-72-9(Hazardous Substances Data)

Usage

Description

Enalaprilat is the diacid active metabolite of enalapril. As an injectable ACE inhibitor, it is reportedly useful in the treatment of uncomplicated accelerated hypertension and hypertensive emergencies. Enalaprilat is more effective in reducing blood pressure in the elderly than in the young, despite the fact that renin activity is lower in old age.

Chemical Properties

White Crystalline Solid

Originator

Merck (USA)

Uses

Different sources of media describe the Uses of 76420-72-9 differently. You can refer to the following data:
1. Enalapril is a ACE (angiotensin-converting enzyme) inhibitor, suggested to be more potent than Captopril (sc-200566). Studies indicate that Enalapril downregulates the expression of IL-β, IL-6, and NF-κB. Further studies show that Enalapril upregulates the expression of VEGF and heme oxygenase-1. Enalaprilat reports demonstrate that the compound has some antioxidant activity, which does not include the PKC-NADPH oxidase pathway.
2. Active metabolite of Enalapril. A nonsulfhydryl dipeptide angiotensin converting enzyme (ACE) inhibitor
3. primary hypertension

Definition

ChEBI: Enalapril in which the ethyl ester group has been hydrolysed to the corresponding carboxylic acid. Enalaprilat is an angiotensin-converting enzyme (ACE) inhibitor and is used (often in the form of its prodrug, enalapril) in the treatment of hypertension an heart failure, for reduction of proteinuria and renal disease in patients with nephropathies, and for the prevention of stroke, myocardial infarction, and cardiac death in high-risk patients. Unlike enalapril, enalaprilat is not absorbed by mouth but is g ven by intravenous injection, usually as the dihydrate.

Brand name

Vasotec (Biovail);Renitec.

InChI:InChI=1/C18H24N2O5.2H2O/c1-12(16(21)20-11-5-8-15(20)18(24)25)19-14(17(22)23)10-9-13-6-3-2-4-7-13;;/h2-4,6-7,12,14-15,19H,5,8-11H2,1H3,(H,22,23)(H,24,25);2*1H2/t12-,14-,15-;;/m0../s1

Upstream product

• 108428-39-3 N--L-alanyl>-L-proline tert butyl ester 
• 84793-24-8 N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine N-carboxyanhydride 
• 147-85-3 L-proline 
• 76095-16-4 Amprace 
• 29375-30-2 (S)-alanyl-(S)-proline tert-butyl ester 
• 710-11-2 2-oxo-4-phenylbutyric acid 
• 121842-75-9 N-carbamyl (R)-2-amino-4-phenylbutyric acid 
• 121842-77-1 (R)-ethyl 2-bromo-4-phenylbutyrate 
• 121842-76-0 (R)-2-bromo-4-phenylbutyric acid 
• 120379-81-9 5-phenylethyl-imidazolidine-2,4-dione 
• 104-53-0 3-phenyl-propionaldehyde 
• 75847-73-3 enalapril 

Relevant articles and documents

In vitro drug metabolism by human carboxylesterase 1: Focus on angiotensin-converting enzyme inhibitors

Carboxylesterase 1 (CES1) is the major hydrolase in human liver. The enzyme is involved in the metabolism of several important therapeutic agents, drugs of abuse, and endogenous compounds. However, no studies have described the role of human CES1 in the activation of two commonly prescribed angiotensinconverting enzyme inhibitors: enalapril and ramipril. Here, we studied recombinant human CES1-and CES2-mediated hydrolytic activation of the prodrug esters enalapril and ramipril, compared with the activation of the known substrate trandolapril. Enalapril, ramipril, and trandolapril were readily hydrolyzed by CES1, but not by CES2. Ramipril and trandolapril exhibited Michaelis-Menten kinetics, while enalapril demonstrated substrate inhibition kinetics. Intrinsic clearances were 1.061, 0.360, and 0.02 ml/min/mg protein for ramipril, trandolapril, and enalapril, respectively. Additionally, we screened a panel of therapeutic drugs and drugs of abuse to assess their inhibition of the hydrolysis of p-nitrophenyl acetate by recombinant CES1 and human liver microsomes. The screening assay confirmed several known inhibitors of CES1 and identified two previously unreported inhibitors: the dihydropyridine calcium antagonist, isradipine, and the immunosuppressive agent, tacrolimus. CES1 plays a role in the metabolism of several drugs used in the treatment of common conditions, including hypertension, congestive heart failure, and diabetes mellitus; thus, there is a potential for clinically relevant drug-drug interactions. The findings in the present study may contribute to the prediction of such interactions in humans, thus opening up possibilities for safer drug treatments. Copyright

Direct monitoring of drug degradation by easy ambient sonic-spray ionization mass spectrometry: The case of enalapril

Using enalapril maleate as a test case, the ability of ambient mass spectrometry, namely, via easy ambient sonic-spray ionization mass spectrometry (EASI-MS), to perform direct monitoring of drug degradation has been tested. Two manufacturing processes were investigated (direct compression and wet granulation), and the formation of degradation products was measured via both EASI-MS and high-performance liquid chromatography with ultraviolet detection for a total period of 18 months. Both techniques provide comparable results, which indicate that direct analysis by ambient mass spectrometric techniques presents a viable alternative for drug degradation monitoring with superior simplicity, throughput, and reliability (no sample manipulation), and comparable quantitative results. In terms of qualitative monitoring, the full mass spectra with intact species provided by EASI-MS allow for comprehensive monitoring of known and unknown (or unexpected) degradation products. Copyright

Rapid conversion of the new angiotensin converting enzyme inhibitor ramipril to its active metabolite in rats

The rate of conversion of ramipril (Hoe 498), a new angiotensin converting enzyme (ACE) inhibitor, to its active metabolite was compared with that of enalapril. After intravenous administration to rats, ramipril was very rapidly desterified to its active moiety, ramiprilat. The ratio of the active metabolite level to the prodrug level in plasma at 5 min after administration was 10.7 for ramipril, which was about 5 times the ratio for enalapril. The in vitro conversion rates of ramipril were higher than those of enalapril in all rat tissue homogenates examined, including the liver, a main site of metabolism. The apparent Km values of ramipril and enalapril in the liver were 190 and 710 μmol/l, respectively, suggesting that ramipril has a higher affinity for esterase than enalapril. In conclusion, ramipril was superior to enalapril in efficiency of conversion to the active metabolite.