Page last updated: 2024-11-11

benazeprilat

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

benazeprilat: structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

benazeprilat : A benzazepine that is 1,3,4,5-tetrahydro-2H-1-benzazepin-2-one in which the hydrogen attached to the nitrogen is replaced by a carboxy methyl group and in which the 3-pro-S hydrogen is replaced by the amino group of (2S)-2-amino-4-phenylbutanoic acid. An angiotensin-converting enzyme inhibitor, it is used as its monoester prodrug benazepril in the treatment of hypertension and heart failure. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID5463984
CHEMBL ID543766
CHEMBL ID1192519
CHEBI ID88200
SCHEMBL ID159245
MeSH IDM0148101

Synonyms (50)

Synonym
benazeprilat (usan/inn)
D03077
86541-78-8
benazeprilate [french]
benazeprilat [usan:inn]
cgs 14831
benazeprilatum [latin]
1h-1-benzazepine-1-acetic acid, 3-((1-carboxy-3-phenylpropyl)amino)-2,3,4,5-tetrahydro-2-oxo-, (s-(r*,r*))-
benazeprilat
1h-1-benzazepine-1-acetic acid, 3-(((1s)-1-carboxy-3-phenylpropyl)amino)-2,3,4,5-tetrahydro-2-oxo-, (3s)-
(3s)-3-(((1s)-1-carboxy-3-phenylpropyl)amino)-2,3,4,5-tetrahydro-2-oxo-1h-1-benzazepine-1-acetic acid
(2s)-2-[[(3s)-1-(carboxymethyl)-2-oxo-4,5-dihydro-3h-1-benzazepin-3-yl]amino]-4-phenylbutanoic acid
chembl543766 ,
2-(1-carboxymethyl-2-oxo-2,3,4,5-tetrahydro-1h-benzo[b]azepin-3-ylamino)-4-phenyl-butyric acid; hydrochloride
bdbm50021127
benazepril diacid
CHEMBL1192519
chebi:88200 ,
unii-jrm708l703
benazeprilate
benazeprilatum
jrm708l703 ,
1h-1-benzazepine-1-aceticacid, 3-[[(1s)-1-carboxy-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-, (3s)-
(3s)-3-[[(1s)-1-carboxy-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-1h-1-benzazepine-1-acetic acid
cgs-14831
benezaprilat
benazeprilat [usan]
benazeprilat [inn]
benazeprilat [who-dd]
benazepril diacid [mi]
benazepril hydrochloride impurity c [ep impurity]
gtpl6375
SCHEMBL159245
(2s)-2-{[(3s)-1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1h-1-benzazepin-3-yl]amino}-4-phenylbutanoic acid
(2s)-2-[[(3s)-1-(carboxymethyl)-2-keto-4,5-dihydro-3h-1-benzazepin-3-yl]amino]-4-phenyl-butyric acid
C21541
AKOS030243065
HY-118472
(2s)-2-[[(3s)-1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1h-1-benzazepin-3-yl]amino]-4-phenylbutanoic acid (benazeprilat)
2-((s)-1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1h-benzo[b]azepin-3-ylamino)-4-phenylbutanoic acid
DB14125
Q27075017
(3s)-[[(1s)-1-carboxy-3-phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-1h-1-benzazepine-1-acetic acid
cgs14831
usp benazepril related compound c
DTXSID501024701
CS-0066056
benazeprilatum (latin)
(2s)-2-(((3s)-1-(carboxymethyl)-2-oxo-2,3,4,5-tetrahydro-1h-1-benzazepin-3-yl)amino)-4-phenylbutanoic acid
benazepril hydrochloride impurity c (ep impurity)

Research Excerpts

Pharmacokinetics

Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. The pharmacokinetic endpoints were plasma concentrations of benazapril and benazEPrilat, and recovery of radioactivity in faeces and urine.

ExcerptReferenceRelevance
" On average, the pharmacokinetic parameters of benazepril and benazeprilat in the patients did not differ from those in a historical control group of healthy volunteers, but intersubject variability in the AUC and half-lives of benazeprilat was greater in the patients."( Pharmacokinetics and pharmacodynamics of benazepril hydrochloride in patients with major proteinuria.
Dieterle, W; Kaiser, G; Mann, J; Schweizer, C, 1993
)
0.53
"Plasma pharmacokinetic variables of benazeprilat, the active metabolite of the angiotensin-converting enzyme (ACE) inhibitor benazepril, were evaluated in healthy Beagles."( Pharmacokinetics of the active metabolite of benazepril, benazeprilat, and inhibition of plasma angiotensin-converting enzyme activity after single and repeated administrations to dogs.
Kaiser, G; King, JN; Mauron, C, 1995
)
0.81
"47, equivalent to a half-life for accumulation (t1/2acc) of 14."( Pharmacokinetics of the angiotensin-converting-enzyme inhibitor, benazepril, and its active metabolite, benazeprilat, in dog.
Kaiser, G; King, JN; Maurer, M; Mauron, C; Morrison, CA, 1997
)
0.51
"The pharmacokinetic disposition of benazeprilat, an angiotensin-converting enzyme (ACE) inhibitor (ACEI), was assessed with a nonlinear binding model in dogs."( Benazeprilat disposition and effect in dogs revisited with a pharmacokinetic/pharmacodynamic modeling approach.
King, JN; Lefebvre, HP; Toutain, PL, 2000
)
2.03
" The pharmacokinetic endpoints were plasma concentrations of benazepril and benazeprilat, and recovery of radioactivity in faeces and urine."( Pharmacokinetic/pharmacodynamic modelling of the disposition and effect of benazepril and benazeprilat in cats.
King, JN; Maurer, M; Toutain, PL, 2003
)
0.77
"Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses."( Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.
Ayala, N; Caballero, JMS; Castejón-Riber, C; Esgueva, M; Gómez-Díez, M; Mena-Bravo, A; Muñoz, A; Priego-Capote, F; Serrano-Rodríguez, JM, 2017
)
0.91

Bioavailability

In patients with hepatic cirrhosis, the kinetics and bioavailability of benazeprilat were not affected. Perorally dosed benazepsilat was poorly absorbed in rats. Systemic bioavailability after PO benazpsil was 3-4%.

ExcerptReferenceRelevance
" Perorally dosed benazeprilat was poorly absorbed in rats, whereas benazepril."( Disposition of [14C]-benazepril hydrochloride in rat, dog and baboon. Absorption, distribution, kinetics, biotransformation and excretion.
Schmid, K; Waldmeier, F, 1989
)
0.62
" A cross-check with a gas chromatographic-mass spectrometric method showed good agreement, demonstrating that this enzymic method is suitable for assessing drug bioavailability and pharmacokinetics."( Determination of the angiotensin converting enzyme inhibitor benazeprilat in plasma and urine by an enzymic method.
Frueh, F; Graf, P; Schmid, K, 1988
)
0.52
" In patients with hepatic cirrhosis, the kinetics and bioavailability of benazeprilat were not affected."( Pharmacokinetics of a new angiotensin-converting enzyme inhibitor, benazepril hydrochloride, in special populations.
Ackermann, R; Kaiser, G; Sioufi, A, 1989
)
0.51
" The method can be used to assess the bioavailability and pharmacokinetics of the drug."( Simultaneous determination of benazepril hydrochloride and benazeprilat in plasma by high-performance liquid chromatography/electrospray-mass spectrometry.
Chen, B; Cheng, Z; Xiao, W; Yao, S, 2005
)
0.57
" The bioavailability of the active compounds from their respective pro-drug is low."( Angiotensin-converting enzyme inhibitors in veterinary medicine.
Brown, SA; Chetboul, V; King, JN; Lefebvre, HP; Pouchelon, JL; Toutain, PL, 2007
)
0.34
" Systemic bioavailability of benazeprilat after PO benazepril was 3-4%."( Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses.
Ayala, N; Caballero, JMS; Castejón-Riber, C; Esgueva, M; Gómez-Díez, M; Mena-Bravo, A; Muñoz, A; Priego-Capote, F; Serrano-Rodríguez, JM, 2017
)
0.99

Dosage Studied

The nonlinear disposition of benazeprilat raised several issues. The concentration profile was only relevant to definition of an optimal dosage regimen if the appropriate kinetic model was used to interpret the plasma data.

ExcerptRelevanceReference
" Thus, there seems to be no need for dosage adjustment of benazepril hydrochloride in patients suffering from cirrhosis of the liver."( The influence of hepatic cirrhosis on the pharmacokinetics of benazepril hydrochloride.
Ackermann, R; Defalco, A; Gschwind, HP; Holmes, IB; James, IM; Kaiser, G; McIntyre, N; Sprengers, D, 1990
)
0.28
" The disposition of both compounds was studied in rat, dog and baboon after peroral and intravenous dosing of 14C-labelled preparations (2."( Disposition of [14C]-benazepril hydrochloride in rat, dog and baboon. Absorption, distribution, kinetics, biotransformation and excretion.
Schmid, K; Waldmeier, F, 1989
)
0.28
" The drug disposition did not change during repeated oral dosing and only small accumulation of the metabolite occurred."( Pharmacokinetics of the angiotensin converting enzyme inhibitor benazepril.HCl (CGS 14 824 A) in healthy volunteers after single and repeated administration.
Ackermann, R; Brechbühler, S; Dieterle, W; Kaiser, G,
)
0.13
"5 and 2 h after dosing (median 1 h)."( Pharmacokinetics and pharmacodynamics of benazepril hydrochloride in patients with major proteinuria.
Dieterle, W; Kaiser, G; Mann, J; Schweizer, C, 1993
)
0.29
" The dosage protocol was based on obtaining a 50% reduction in angiotensin I and angiotensin II pressor response with no significant effects on mean basal arterial pressure."( Angiotensin AT1 receptor inhibition, angiotensin-converting enzyme inhibition, and combination therapy with developing heart failure: cellular mechanisms of action.
de Gasparo, M; Iannini, JP; Melton, DM; Mukherjee, R; Spinale, FG, 1998
)
0.3
" The nonlinear disposition of benazeprilat raised several issues and it was concluded that the benazeprilat concentration profile was only relevant to definition of an optimal dosage regimen if the appropriate kinetic model was used to interpret the plasma data."( Benazeprilat disposition and effect in dogs revisited with a pharmacokinetic/pharmacodynamic modeling approach.
King, JN; Lefebvre, HP; Toutain, PL, 2000
)
2.04
" Benazepril seemed to have a high safety, and the adjustment of dosage regimen might not be needed in dogs with mild to moderate renal function impairment because the drug was excreted both from the kidneys and liver."( Plasma concentrations of an angiotensin-converting enzyme inhibitor, benazepril, and its active metabolite, benazeprilat, after repeated administrations of benazepril in dogs with experimental kidney impairment.
Eguchi, T; Kitagawa, H; Kitoh, K; Kondo, M; Nakano, M; Ohba, Y; Sasaki, Y, 2000
)
0.52
" The method was applied to the assay of BNZ in combined dosage form with no interference from other ingredients."( Kinetic Profiling of the Hydrolytic Reaction of Benazepril: Metabolic Pathway Simulation.
Hemdan, A; Michael, AM, 2018
)
0.48
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitorAn EC 3.4.15.* (peptidyl-dipeptidase) inhibitor that interferes with the action of peptidyl-dipeptidase A (EC 3.4.15.1).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (3)

ClassDescription
benzazepineA group of two-ring heterocyclic compounds consisting of a benzene ring fused to an azepine ring.
dicarboxylic acidAny carboxylic acid containing two carboxy groups.
lactamCyclic amides of amino carboxylic acids, having a 1-azacycloalkan-2-one structure, or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (2)

PathwayProteinsCompounds
Benazepril Action Pathway34
Benazepril Metabolism Pathway12

Protein Targets (1)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Angiotensin-converting enzymeOryctolagus cuniculus (rabbit)IC50 (µMol)0.00200.00001.612910.0000AID37785
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (9)

Assay IDTitleYearJournalArticle
AID38111Evaluation of plasma inhibition of Angiotensin I converting enzyme activity in conscious rat 1 hour after ia administration at a dose of 10 mg/kg1995Journal of medicinal chemistry, Dec-22, Volume: 38, Issue:26
New alpha-thiol dipeptide dual inhibitors of angiotensin-I converting enzyme and neutral endopeptidase EC 3.4.24.11.
AID184931Tested for the inhibition of angiotensin I (AI) pressor response after 2 hours following an oral dose of 10 mg/kg1993Journal of medicinal chemistry, Nov-26, Volume: 36, Issue:24
Heterocyclic lactam derivatives as dual angiotensin converting enzyme and neutral endopeptidase 24.11 inhibitors.
AID38120Evaluation of plasma inhibition of Angiotensin I converting enzyme activity in conscious rat 4 hours after ia administration at a dose of 10 mg/kg1995Journal of medicinal chemistry, Dec-22, Volume: 38, Issue:26
New alpha-thiol dipeptide dual inhibitors of angiotensin-I converting enzyme and neutral endopeptidase EC 3.4.24.11.
AID184930Tested for the inhibition of angiotensin I (AI) pressor response after 1 hour following an oral dose of 10 mg/kg1993Journal of medicinal chemistry, Nov-26, Volume: 36, Issue:24
Heterocyclic lactam derivatives as dual angiotensin converting enzyme and neutral endopeptidase 24.11 inhibitors.
AID38116Evaluation of plasma inhibition of Angiotensin I converting enzyme activity in conscious rat 2 hours after ia administration at a dose of 10 mg/kg1995Journal of medicinal chemistry, Dec-22, Volume: 38, Issue:26
New alpha-thiol dipeptide dual inhibitors of angiotensin-I converting enzyme and neutral endopeptidase EC 3.4.24.11.
AID37785Tested in vitro for the inhibition against angiotensin converting enzyme (ACE) from rabbit lung1993Journal of medicinal chemistry, Nov-26, Volume: 36, Issue:24
Heterocyclic lactam derivatives as dual angiotensin converting enzyme and neutral endopeptidase 24.11 inhibitors.
AID184929Tested for the inhibition of angiotensin I (AI) pressor response after 0.5 hour following an oral dose of 10 mg/kg1993Journal of medicinal chemistry, Nov-26, Volume: 36, Issue:24
Heterocyclic lactam derivatives as dual angiotensin converting enzyme and neutral endopeptidase 24.11 inhibitors.
AID38245Evaluation of plasma inhibition of Angiotensin I converting enzyme activity in conscious rat 6 hours after ia administration at a dose of 10 mg/kg1995Journal of medicinal chemistry, Dec-22, Volume: 38, Issue:26
New alpha-thiol dipeptide dual inhibitors of angiotensin-I converting enzyme and neutral endopeptidase EC 3.4.24.11.
AID1345457Human Angiotensin-converting enzyme (M2: Angiotensin-converting (ACE and ACE2))2007Current pharmaceutical design, , Volume: 13, Issue:13
Angiotensin-converting enzyme inhibitors in veterinary medicine.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (68)

TimeframeStudies, This Drug (%)All Drugs %
pre-19908 (11.76)18.7374
1990's36 (52.94)18.2507
2000's15 (22.06)29.6817
2010's9 (13.24)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 89.53

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index89.53 (24.57)
Research Supply Index4.33 (2.92)
Research Growth Index4.88 (4.65)
Search Engine Demand Index157.97 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (89.53)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials6 (8.70%)5.53%
Reviews2 (2.90%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other61 (88.41%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]