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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H26N2O5.H2O
Molecular Weight 428.4791
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of QUINAPRILAT HYDRATE

SMILES

C[C@@]([H])(C(=O)N1Cc2ccccc2C[C@@]1([H])C(=O)O)N[C@@]([H])(CCc3ccccc3)C(=O)O.O

InChI

InChIKey=OFYSYEOWQQCPEU-ZAFWUOJLSA-N
InChI=1S/C23H26N2O5.H2O/c1-15(24-19(22(27)28)12-11-16-7-3-2-4-8-16)21(26)25-14-18-10-6-5-9-17(18)13-20(25)23(29)30;/h2-10,15,19-20,24H,11-14H2,1H3,(H,27,28)(H,29,30);1H2/t15-,19-,20-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C23H26N2O5
Molecular Weight 410.4638
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT00651287 | https://www.ncbi.nlm.nih.gov/pubmed/25922179 | https://www.ncbi.nlm.nih.gov/pubmed/1691409

Quinapril is the hydrochloride salt of quinapril, the ethyl ester of a non-sulfhydryl, angiotensin-converting enzyme (ACE) inhibitor, quinaprilat. Quinapril hydrochloride is a white to off-white amorphous powder that is freely soluble in aqueous solvents. Quinapril is indicated for the treatment of high blood pressure (hypertension) and as adjunctive therapy in the management of heart failure. It may be used for the treatment of hypertension by itself or in combination with thiazide diuretics, and with diuretics and digoxin for heart failure.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.8 nM [IC50]
110.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ACCURETIC

Approved Use

INDICATIONS AND USA. Hypertension: ACCURETIC is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with ACCURETIC. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. 6 Reference ID: 3818285 Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. This fixed combination is not indicated for the initial therapy of hypertension (see DOSAGE AND ADMINISTRATION). In using ACCURETIC, consideration should be given to the fact that another angiotensinconverting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that quinapril does not have a similar risk (see WARNINGS: Neutropenia/Agranulocytosis). Angioedema in Black Patients: Black patients receiving ACE inhibitor monotherapy have been reported to have a higher incidence of angioedema compared to non-blacks. It should also be noted that in controlled clinical trials, ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks.

Launch Date

9.4625281E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1526 ng/mL
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
QUINAPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
345 ng/mL
2.5 mg single, intravenous
dose: 2.5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
QUINAPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1706 μg × h/L
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
QUINAPRILAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2670 ng × h/mL
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
QUINAPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
580 ng × h/mL
2.5 mg single, intravenous
dose: 2.5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
QUINAPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.7 h
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
QUINAPRILAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.29 h
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
QUINAPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
2.26 h
2.5 mg single, intravenous
dose: 2.5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
QUINAPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 11
unhealthy, adult
n = 1563
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 1563
Sources: Page: 11
Disc. AE: Headache, Dizziness...
AEs leading to
discontinuation/dose reduction:
Headache (0.7%)
Dizziness (0.8%)
Fatigue (0.3%)
Coughing (0.5%)
Nausea and vomiting (0.3%)
Abdominal pain (0.2%)
Sources: Page: 11
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 12
unhealthy, adult
n = 585
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 585
Sources: Page: 12
Disc. AE: Dizziness, Coughing...
AEs leading to
discontinuation/dose reduction:
Dizziness (0.7%)
Coughing (0.3%)
Fatigue (0.2%)
Nausea and vomiting (0.2%)
Hypotension (0.5%)
Dyspnea (0.2%)
Rash (0.2%)
Sources: Page: 12
AEs

AEs

AESignificanceDosePopulation
Abdominal pain 0.2%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 11
unhealthy, adult
n = 1563
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 1563
Sources: Page: 11
Fatigue 0.3%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 11
unhealthy, adult
n = 1563
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 1563
Sources: Page: 11
Nausea and vomiting 0.3%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 11
unhealthy, adult
n = 1563
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 1563
Sources: Page: 11
Coughing 0.5%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 11
unhealthy, adult
n = 1563
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 1563
Sources: Page: 11
Headache 0.7%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 11
unhealthy, adult
n = 1563
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 1563
Sources: Page: 11
Dizziness 0.8%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 11
unhealthy, adult
n = 1563
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 1563
Sources: Page: 11
Dyspnea 0.2%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 12
unhealthy, adult
n = 585
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 585
Sources: Page: 12
Fatigue 0.2%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 12
unhealthy, adult
n = 585
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 585
Sources: Page: 12
Nausea and vomiting 0.2%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 12
unhealthy, adult
n = 585
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 585
Sources: Page: 12
Rash 0.2%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 12
unhealthy, adult
n = 585
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 585
Sources: Page: 12
Coughing 0.3%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 12
unhealthy, adult
n = 585
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 585
Sources: Page: 12
Hypotension 0.5%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 12
unhealthy, adult
n = 585
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 585
Sources: Page: 12
Dizziness 0.7%
Disc. AE
40 mg 1 times / day multiple, oral (max)
Recommended
Dose: 40 mg, 1 times / day
Route: oral
Route: multiple
Dose: 40 mg, 1 times / day
Sources: Page: 12
unhealthy, adult
n = 585
Health Status: unhealthy
Condition: Hypertension
Age Group: adult
Sex: M+F
Population Size: 585
Sources: Page: 12
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 6.2 uM]
Drug as victim
PubMed

PubMed

TitleDatePubMed
Preservation of cardiac function and energy reserve by the angiotensin-converting enzyme inhibitor quinapril during postmyocardial infarction remodeling in the rat.
2001
Quinapril with high affinity to tissue angiotensin-converting enzyme reduces restenosis after percutaneous transcatheter coronary intervention.
2001 Jul
The influence of angiotensin-converting enzyme inhibitors on the aorta elastin metabolism in diet-induced hypercholesterolaemia in rabbits.
2001 Mar
Inhibition of progression of heart failure and expression of TGF-beta 1 mRNA in rats with heart failure by the ACE inhibitor quinapril.
2001 Oct
[Some new data concerning effectiveness of amlodipine, atorvastatine and quinaprile for heart diseases].
2002
[Clinical sequelae of tissue angiotensin converting enzyme inhibition: practicability of use in ischemic heart disease].
2002
Angiotensin II induced inflammation in the kidney and in the heart of double transgenic rats.
2002
Rapid increase in cardiac adrenomedullin gene expression caused by acute pressure overload: effect of the renin-angiotensin system on gene expression.
2002 Apr
Quinapril prevents restenosis after coronary stenting in patients with angiotensin-converting enzyme D allele.
2002 Apr
Inhibition of left ventricular fibrosis by tranilast in rats with renovascular hypertension.
2002 Apr
[Is mild essential hypertension without obvious organ complications and risk factors associated with increased levels of circulating markers of endothelial dysfunction? Effect of ACE inhibitor therapy].
2002 Aug
AT1 receptor blockade increases cardiac bradykinin via neutral endopeptidase after induction of myocardial infarction in rats.
2002 Aug
Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors.
2002 Aug
Using ACE inhibitors appropriately.
2002 Aug 1
Enalapril and quinapril improve endothelial vasodilator function and aortic eNOS gene expression in L-NAME-treated rats.
2002 Aug 16
Time-effect profile of antihypertensive agents assessed with trough/peak ratio, smoothness index and dose omission: an ambulatory blood pressure monitoring study with trandolapril vs. quinapril.
2002 Dec
The ACE inhibitor, quinapril, ameliorates peritoneal fibrosis in an encapsulating peritoneal sclerosis model in mice.
2002 Dec
Effects of antihypertensive drugs in experimental type 2 diabetes-related nephropathy.
2002 Dec
Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney.
2002 Dec
Influence of angiotensinogen M253T gene polymorphism and an angiotensin converting enzyme inhibitor on restenosis after percutaneous coronary intervention.
2002 Feb
Effects of chronic administration of sarpogrelate on systolic blood pressure of spontaneously hypertensive rats: comparison with quinapril.
2002 Feb
Angiotensin II as an inflammatory mediator: evolving concepts in the role of the renin angiotensin system in the failing heart.
2002 Jan
Effects of quinapril on myocardial function, ventricular remodeling and cardiac cytokine expression in congestive heart failure in the rat.
2002 Jan
Effects of a citrate buffer system on the solid-state chemical stability of lyophilized quinapril preparations.
2002 Jan
Determination of the angiotensin-converting enzyme inhibitor quinapril and its metabolite quinaprilat in pharmaceuticals and urine by capillary zone electrophoresis and solid-phase extraction.
2002 Jan
Psychological characteristics and responses to antihypertensive drug therapy.
2002 Jan-Feb
The mechanism of the angiotensin-converting enzyme inhibitor quinapril is not related to bradykinin level in heart tissue.
2002 Jun
Subacute and chronic effects of quinapril on cardiac cytokine expression, remodeling, and function after myocardial infarction in the rat.
2002 Jun
Blockade of endothelial enzymes: new therapeutic targets.
2002 Mar
Effects of a long-term pharmacological interruption of the renin-angiotensin system on the fibrinolytic system in essential hypertension.
2002 Mar-Apr
Ventricular remodeling after myocardial infarction and effects of ACE inhibition on hemodynamics and scar formation in SHR.
2002 Mar-Apr
Lowering of blood pressure improves endothelial dysfunction by increase of nitric oxide production in hypertensive rats.
2002 May
Pretreatment with angiotensin-converting enzyme inhibitors attenuates ischemia-reperfusion injury.
2002 May
Bradykinin as a major endogenous regulator of endothelial function.
2002 May-Jun
Quinapril treatment restores the vasodilator action of insulin in fructose-hypertensive rats.
2002 May-Jun
Ischemia Management with Accupril post bypass Graft via Inhibition of angiotensin coNverting enzyme (IMAGINE): a multicentre randomized trial - design and rationale.
2002 Nov
Effect of losartan on nocturnal blood pressure in patients with stroke: comparison with angiotensin converting enzyme inhibitor.
2002 Nov
Optimisation by experimental design of a capillary electrophoretic method for the separation of several inhibitors of angiotensin-converting enzyme using alkylsulphonates.
2002 Nov 29
Captopril and quinapril reduce reactive oxygen species.
2002 Oct
Prevention of vascular damage in scleroderma with angiotensin-converting enzyme (ACE) inhibition.
2002 Sep
[Angiotensin-converting enzyme, quinapril, in treating chronic cardiac failure].
2003
Role of PKC in autocrine regulation of rat ventricular K+ currents by angiotensin and endothelin.
2003 Apr
Pharmacokinetics of quinapril in children: assessment during substitution for chronic angiotensin-converting enzyme inhibitor treatment.
2003 Feb
Comparative effects of angiotensin II receptor blockade (candesartan) with angiotensin-converting enzyme inhibitor (quinapril) in rats with dilated cardiomyopathy.
2003 Jan
Attenuation of heart failure due to coronary stenosis by ACE inhibitor and angiotensin receptor blocker.
2003 Jul
Improvement of endothelial dysfunction by angiotensin II blockade accompanied by induction of vascular hepatocyte growth factor system in diabetic spontaneously hypertensive rats.
2003 Mar
Square wave voltammetric determination of the angiotensin-converting enzyme inhibitors cilazapril, quinapril and ramipril in pharmaceutical formulations.
2003 May
Usefulness of quinapril and irbesartan to improve the anti-inflammatory response of atorvastatin and aspirin in patients with coronary heart disease.
2003 May 1
In vitro study on binding interaction of quinapril with bovine serum albumin (BSA) using multi-spectroscopic and molecular docking methods.
2017 Aug
Genetic variants associated with angiotensin-converting enzyme inhibitor-induced cough: a genome-wide association study in a Swedish population.
2017 Feb
Patents

Sample Use Guides

The recommended initial dosage of ACCUPRIL in patients not on diuretics is 10 or 20 mg once daily. Dosage should be adjusted according to blood pressure response measured at peak (2–6 hours after dosing) and trough (predosing). Generally, dosage adjustments should be made at intervals of at least 2 weeks. Most patients have required dosages of 20, 40, or 80 mg/day, given as a single dose or in two equally divided doses.
Route of Administration: Oral
In Vitro Use Guide
Unknown
Substance Class Chemical
Created
by admin
on Sat Jun 26 06:46:39 UTC 2021
Edited
by admin
on Sat Jun 26 06:46:39 UTC 2021
Record UNII
3P66XFG826
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
QUINAPRILAT HYDRATE
WHO-DD  
Common Name English
QUINAPRILAT HYDRATE [WHO-DD]
Common Name English
3-ISOQUINOLINECARBOXYLIC ACID, 2-(2-((1-CARBOXY-3-PHENYLPROPYL)AMINO)-1-OXOPROPYL)-1,2,3,4-TETRAHYDRO-, (3S-(2(R*(R*)),3R*))-, MONOHYDRATE
Common Name English
Code System Code Type Description
FDA UNII
3P66XFG826
Created by admin on Sat Jun 26 06:46:39 UTC 2021 , Edited by admin on Sat Jun 26 06:46:39 UTC 2021
PRIMARY
PUBCHEM
25030442
Created by admin on Sat Jun 26 06:46:39 UTC 2021 , Edited by admin on Sat Jun 26 06:46:39 UTC 2021
PRIMARY
CAS
1435786-09-6
Created by admin on Sat Jun 26 06:46:39 UTC 2021 , Edited by admin on Sat Jun 26 06:46:39 UTC 2021
PRIMARY
DRUG BANK
DBSALT002763
Created by admin on Sat Jun 26 06:46:39 UTC 2021 , Edited by admin on Sat Jun 26 06:46:39 UTC 2021
PRIMARY
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ACTIVE MOIETY