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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H34NO5P
Molecular Weight 435.4944
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOSINOPRILAT

SMILES

c1ccc(cc1)CCCCP(=O)(CC(=O)N2C[C@@]([H])(C[C@@]2([H])C(=O)O)C3CCCCC3)O

InChI

InChIKey=WOIWWYDXDVSWAZ-RTWAWAEBSA-N
InChI=1S/C23H34NO5P/c25-22(17-30(28,29)14-8-7-11-18-9-3-1-4-10-18)24-16-20(15-21(24)23(26)27)19-12-5-2-6-13-19/h1,3-4,9-10,19-21H,2,5-8,11-17H2,(H,26,27)(H,28,29)/t20-,21+/m1/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/pro/fosinopril.html

Fosinopril is a phosphinic acid-containing ester prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly hydrolyzed to fosinoprilat, its principle active metabolite. Fosinoprilat inhibits ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Fosinopril may be used to treat mild to moderate hypertension, as an adjunct in the treatment of congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.

CNS Activity

Curator's Comment:: Fosinopril does not cross the blood-brain barrier.

Originator

Curator's Comment:: # Bristol-Myers Squibb

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.0 nM [IC50]
Target ID: P12822
Gene ID: 1.00009272E8
Gene Symbol: ACE
Target Organism: Oryctolagus cuniculus (Rabbit)
11.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
FOSINOPRIL SODIUM

Approved Use

Fosinopril sodium tablets are indicated for the treatment of hypertension. They may be used alone or in combination with thiazide diuretics. Fosinopril sodium tablets are indicated in the management of heart failure as adjunctive therapy when added to conventional therapy including diuretics with or without digitalis

Launch Date

1.07015039E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1556 ng/mL
7.5 mg single, intravenous
dose: 7.5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FOSINOPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
112 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
533 ng/mL
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
711 ng/mL
40 mg 2 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1018 ng/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1217 ng/mL
80 mg 2 times / day steady-state, oral
dose: 80 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
131 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5598 ng/mL
640 mg single, oral
dose: 640 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3302 ng × h/mL
7.5 mg single, intravenous
dose: 7.5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FOSINOPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
920 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
3.3 μg × h/mL
40 mg single, oral
dose: 40 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
4.9 μg × h/mL
40 mg 2 times / day steady-state, oral
dose: 40 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5.6 μg × h/mL
80 mg single, oral
dose: 80 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
7.5 μg × h/mL
80 mg 2 times / day steady-state, oral
dose: 80 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1.1 μg × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
58.3 μg × h/mL
640 mg single, oral
dose: 640 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.7 h
7.5 mg single, intravenous
dose: 7.5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FOSINOPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
4.3 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
5%
7.5 mg single, intravenous
dose: 7.5 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FOSINOPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
8%
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FOSINOPRILAT plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
80 mg 1 times / day multiple, oral
Highest studied dose
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, 28 - 68years
n = 12
Health Status: unhealthy
Condition: essential hypertension
Age Group: 28 - 68years
Sex: M+F
Population Size: 12
Sources:
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: 16
unhealthy, >65 years
n = 688
Health Status: unhealthy
Condition: hypertension
Age Group: >65 years
Sex: unknown
Population Size: 688
Sources: Page: 16
Disc. AE: Headache, Transaminases increased...
AEs leading to
discontinuation/dose reduction:
Headache (0.4 - 0.9)
Transaminases increased (0.4 - 0.9)
Fatigue (0.4 - 0.9)
Cough (0.4 - 0.9)
Sources: Page: 16
40 mg 1 times / day steady, oral
MTD
Dose: 40 mg, 1 times / day
Route: oral
Route: steady
Dose: 40 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: hypertension
Age Group: adult
Sex: unknown
Sources:
AEs

AEs

AESignificanceDosePopulation
Cough 0.4 - 0.9
Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: 16
unhealthy, >65 years
n = 688
Health Status: unhealthy
Condition: hypertension
Age Group: >65 years
Sex: unknown
Population Size: 688
Sources: Page: 16
Fatigue 0.4 - 0.9
Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: 16
unhealthy, >65 years
n = 688
Health Status: unhealthy
Condition: hypertension
Age Group: >65 years
Sex: unknown
Population Size: 688
Sources: Page: 16
Headache 0.4 - 0.9
Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: 16
unhealthy, >65 years
n = 688
Health Status: unhealthy
Condition: hypertension
Age Group: >65 years
Sex: unknown
Population Size: 688
Sources: Page: 16
Transaminases increased 0.4 - 0.9
Disc. AE
20 mg 1 times / day multiple, oral
Recommended
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources: Page: 16
unhealthy, >65 years
n = 688
Health Status: unhealthy
Condition: hypertension
Age Group: >65 years
Sex: unknown
Population Size: 688
Sources: Page: 16
PubMed

PubMed

TitleDatePubMed
Fosinopril, a phosphinic acid inhibitor of angiotensin I converting enzyme: in vitro and preclinical in vivo pharmacology.
1989 Nov
[Effects of lorsartan, fosinopril on myocardial fibrosis, angiotensin II and cardiac remolding in hypertensive rats].
2001 Apr 28
[Contrast of losartan, fosinopril and amlodipine on cardiomyocyte apoptosis and left ventricular remolding in hypertensive rats].
2001 Oct 28
The effect and mechanism of forsinopril on ventricular hypertrophy of SHR and left ventricular pressure overloading rat.
2002
[FLAG--a program of achievability of target blood pressure levels during treatment of patients with hypertension with fosinopril].
2002
[Changes of distensibility of the aorta in elderly patients during long-term therapy with various classes of hypotensive drugs (magnetic resonance tomography data)].
2002
Using ACE inhibitors appropriately.
2002 Aug 1
Regression of ventricular and vascular hypertrophy: are there differences between structurally different angiotensin-converting enzyme inhibitors?
2002 Dec
Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism.
2002 Dec
Effects of amlodipine fosinopril combination on microalbuminuria in hypertensive type 2 diabetic patients.
2002 Dec
[Effect of Erigeron breviscapus injection on ventricular and vascular remodeling in spontaneous hypertension rats].
2002 Feb
[Renoprotective effect of monopril in patients with diabetes mellitus in the preclinical stage of diabetic nephropathy].
2002 Jul-Sep
Safe drug prescribing.
2002 Jun 25
Fosinopril improves left ventricular diastolic function in young mildly hypertensive patients without hypertrophy.
2002 Mar
Fixed combinations of delapril plus indapamide vs fosinopril plus hydrochlorothiazide in mild to moderate essential hypertension.
2002 May-Jun
[Comparison of the antihypertensive activity of fosinopril and irbesartan].
2002 Nov
FOSIDIAL: a randomised placebo controlled trial of the effects of fosinopril on cardiovascular morbidity and mortality in haemodialysis patients. Study design and patients' baseline characteristics.
2002 Oct
Hemodynamic and humoral effects of vasopeptidase inhibition in canine hypertension.
2002 Oct
Physiologic consequences of vasopeptidase inhibition in humans: effect of sodium intake.
2002 Oct
The effects of losartan and fosinopril in hypertensive type 2 diabetic patients.
2002 Oct
Gateways to Clinical Trials.
2002 Sep
[Efficacy of combined use of fosinopril and propranolol in acute myocardial infarction].
2003
[Chronopharmacological approaches to the therapeutic prophylaxis of chronic cardiac insufficiency in type I diabetes mellitus].
2003
Acute visual loss after initiation of antihypertensive therapy: case report.
2003 Aug 19
A prospective, randomized, open labeled crossover trial of fosinopril and theophylline in post renal transplant erythrocytosis.
2003 Jan
Effects of fosinopril and valsartan on expressions of ICAM-1 and NO in human umbilical vein endothelial cells.
2003 Jun
Effect of xuezhikang, a cholestin extract, on reflecting postprandial triglyceridemia after a high-fat meal in patients with coronary heart disease.
2003 Jun
Effect of dual angiotensin converting enzyme/neutral endopeptidase inhibition, angiotensin converting enzyme inhibition, or AT1 antagonism on coronary microvasculature in spontaneously hypertensive rats.
2003 Nov
Angiotensin-converting enzyme inhibition but not angiotensin II receptor blockade regulates matrix metalloproteinase activity in patients with glomerulonephritis.
2003 Nov
Ramipril-associated hepatotoxicity.
2003 Nov
Protection of organic trauma in sinoaortic-denervated rats treated with fosinopril.
2003 Oct
Introduction to monitoring. What is what you prescribed actually doing?
2003 Oct
Long-term renal survival in HIV-associated nephropathy with angiotensin-converting enzyme inhibition.
2003 Oct
Precipitation of PTSD with metoprolol for hypertension.
2003 Sep-Oct
[Effects of carvedilol, atenolol and their combination with fosinopril on cardiac rhythm variability, clinicofunctional status and quality of life in patients with postinfarction left ventricular dysfunction].
2004
Systemic contact dermatitis due to captopril without cross-sensitivity to fosinopril, quinapril and benazepril.
2004
American Heart Association scientific sessions.
2004 Apr
Clinical trials update from the European Society of Cardiology Heart Failure meeting: SHAPE, BRING-UP 2 VAS, COLA II, FOSIDIAL, BETACAR, CASINO and meta-analysis of cardiac resynchronisation therapy.
2004 Aug
Heart failure and first dose hypotension after angiotensin converting enzyme inhibitors.
2004 Dec
[Changes of collagen expression of pulmonary arteries and heart ventricles and intervention of fosinopril and losartan in rats with heart failure].
2004 Dec 2
Cardiorenal protective effects of vasopeptidase inhibition with omapatrilat in hypertensive transgenic (mREN-2)27 rats.
2004 Jan
Fosinopril and amlodipine in the treatment of isolated systolic hypertension.
2004 Jan-Feb
Mortality rates in elderly patients who take different angiotensin-converting enzyme inhibitors after acute myocardial infarction: a class effect?
2004 Jul 20
Normalization of renal aquaporin-2 water channel expression by fosinopril, valsartan, and combination therapy in congestive heart failure: a new mechanism of action.
2004 Mar
Framingham score and microalbuminuria: combined future targets for primary prevention?
2004 Nov
Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria.
2004 Nov 2
Therapeutic approaches in the prevention of cardiovascular disease in metabolic syndrome and in patients with type 2 diabetes.
2004 Sep
Is the extrapolated adult dose of fosinopril safe and effective in treating hypertensive children?
2004 Sep
Lithium toxicity after switch from fosinopril to lisinopril.
2005 Mar
Effects of fosinopril and pravastatin on carotid intima-media thickness in subjects with increased albuminuria.
2005 Mar
Patents

Sample Use Guides

Usual Adult Dose for Hypertension Initial dose: 10 mg orally once a day alone or in combination with a diuretic Maintenance dose: 20 to 40 mg orally once a day; some patients may have further response at 80 mg once a day Usual Adult Dose for Congestive Heart Failure Initial dose: 10 mg orally once a day Target dose range: 20 to 40 mg orally once a day Maximum dose: 40 mg orally once a day
Route of Administration: Oral
Fosinopril up-regulated klotho mRNA in NRK-52E cells pretreated with Fos(10(-5) mol/L) for 12 h incubated with AngII
Name Type Language
FOSINOPRILAT
INN   USAN  
USAN   INN  
Official Name English
FOSINOPRILAT [USAN]
Common Name English
(4S)-4-CYCLOHEXYL-1-((HYDROXY(4-PHENYLBUTYL)PHOSPHINYL)ACETYL)-L-PROLINE
Systematic Name English
FOSINOPRILAT [INN]
Common Name English
SQ 27,519
Code English
L-PROLINE, 4-CYCLOHEXYL-1-((HYDROXY(4-PHENYLBUTYL)PHOSPHINYL)ACETYL)-, TRANS-
Systematic Name English
FOSINOPRILIC ACID
Common Name English
FOSFENOPRIL
Common Name English
SQ-27519
Code English
FOSINOPRIL DIACID [MI]
Common Name English
FOSINOPRIL RELATED COMPOUND A [USP-RS]
Common Name English
FOSINOPRIL RELATED COMPOUND A
USP-RS  
Common Name English
FOSINOPRIL DIACID
MI  
Common Name English
SO-27519
Code English
Classification Tree Code System Code
NDF-RT N0000175562
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
NCI_THESAURUS C247
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
Code System Code Type Description
MESH
C046965
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY
NCI_THESAURUS
C65762
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY
IUPHAR
6457
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY
FDA UNII
S312EY6ZT8
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY
EVMPD
SUB07800MIG
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY
USP_CATALOG
1283415
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY USP-RS
MERCK INDEX
M5553
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL581
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY
RXCUI
1546393
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY RxNorm
DRUG BANK
DB14207
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY
INN
6555
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY
PUBCHEM
62956
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY
CAS
95399-71-6
Created by admin on Sat Jun 26 00:44:22 UTC 2021 , Edited by admin on Sat Jun 26 00:44:22 UTC 2021
PRIMARY