U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C30H46NO7P
Molecular Weight 563.6625
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FOSINOPRIL

SMILES

CCC(=O)O[C@@H](O[P@](=O)(CCCCC1=CC=CC=C1)CC(=O)N2C[C@@H](C[C@H]2C(O)=O)C3CCCCC3)C(C)C

InChI

InChIKey=BIDNLKIUORFRQP-XYGFDPSESA-N
InChI=1S/C30H46NO7P/c1-4-28(33)37-30(22(2)3)38-39(36,18-12-11-15-23-13-7-5-8-14-23)21-27(32)31-20-25(19-26(31)29(34)35)24-16-9-6-10-17-24/h5,7-8,13-14,22,24-26,30H,4,6,9-12,15-21H2,1-3H3,(H,34,35)/t25-,26+,30+,39-/m1/s1

HIDE SMILES / InChI

Molecular Formula C30H46NO7P
Molecular Weight 563.6625
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

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

2003
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
The hemodynamic effects of long-term ACE inhibition with fosinopril in patients with heart failure. Fosinopril Hemodynamics Study Group.
1999 Jul
Elevation of serum creatinine following fosinopril therapy.
1999 Mar
Cocaine, HIV, and their cardiovascular effects: is there a role for ACE-inhibitor therapy?
2000 Dec 22
Effect of valsartan and fosinopril on catecholamine-induced cardiac hypertrophy.
2000 Sep
Effects of omapatrilat on blood pressure and insulin sensitivity in an animal model of insulin resistance.
2001
Hepatotoxicity induced by fosinopril.
2001 Aug
Endogenous natriuretic peptides participate in renal and humoral actions of acute vasopeptidase inhibition in experimental mild heart failure.
2001 Aug
Vasopeptidase inhibition attenuates the progression of renal injury in subtotal nephrectomized rats.
2001 Aug
Diverse effects of chronic treatment with losartan, fosinopril, and amlodipine on apoptosis, angiotensin II in the left ventricle of hypertensive rats.
2001 Dec
Fenofibrate and warfarin interaction.
2001 Jul
The quantitative determination of several inhibitors of the angiotensin-converting enzyme by CE.
2001 Jul
Simultaneous determination of hydrochlorothiazide and several inhibitors of angiotensin-converting enzyme by capillary electrophoresis.
2001 Jul 27
Comparison of the first dose response of fosinopril and captopril in congestive heart failure: a randomized, double-blind, placebo controlled study.
2001 Mar
A random comparison of fosinopril and nifedipine GITS in patients with primary renal disease.
2001 Oct
Effects of combination of angiotensin-converting enzyme inhibitor and angiotensin receptor antagonist on inflammatory cellular infiltration and myocardial interstitial fibrosis after acute myocardial infarction.
2001 Oct
Mechanism of intestinal absorption and renal reabsorption of an orally active ace inhibitor: uptake and transport of fosinopril in cell cultures.
2001 Oct
[Contrast of losartan, fosinopril and amlodipine on cardiomyocyte apoptosis and left ventricular remolding in hypertensive rats].
2001 Oct 28
Angiotensin-converting enzyme inhibition induces apoptosis in erythroid precursors and affects insulin-like growth factor-1 in posttransplantation erythrocytosis.
2001 Sep
[FLAG--a program of achievability of target blood pressure levels during treatment of patients with hypertension with fosinopril].
2002
Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update.
2002
Using ACE inhibitors appropriately.
2002 Aug 1
[Effect of Erigeron breviscapus injection on ventricular and vascular remodeling in spontaneous hypertension rats].
2002 Feb
Current recommendations for the treatment of hypertension: are they still valid?
2002 Feb
Fosinopril versus amlodipine comparative treatments study: a randomized trial to assess effects on plasminogen activator inhibitor-1.
2002 Jan 29
[Comparison of the antihypertensive activity of fosinopril and irbesartan].
2002 Nov
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
[Tongue angioedema associated with angiotensin-converting enzyme inhibitor (diagnosis, differential diagnosis, treatment)].
2003
Acute visual loss after initiation of antihypertensive therapy: case report.
2003 Aug 19
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
[Combination therapy with losartan and fosinopril for early diabetic nephropathy].
2003 Sep
Systemic contact dermatitis due to captopril without cross-sensitivity to fosinopril, quinapril and benazepril.
2004
Studies on the glycemic and lipidemic effect of monopril and losartan in normal and diabetic rats.
2004 Aug
Heart failure and first dose hypotension after angiotensin converting enzyme inhibitors.
2004 Dec
Different effects of antihypertensive regimens based on fosinopril or hydrochlorothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atherosclerosis: principal results of PHYLLIS--a randomized double-blind trial.
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
Role of Angiotensin-converting enzyme and neutral endopeptidase in flow-dependent remodeling.
2004 Mar-Apr
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
A unique form of polycythemia associated with minimal change disease.
2004 Nov-Dec
Lithium toxicity after switch from fosinopril to lisinopril.
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
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:23:55 GMT 2023
Edited
by admin
on Fri Dec 15 16:23:55 GMT 2023
Record UNII
R43D2573WO
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FOSINOPRIL
INN   MI   ORANGE BOOK   VANDF   WHO-DD  
INN  
Official Name English
FOSINOPRIL [ORANGE BOOK]
Common Name English
fosinopril [INN]
Common Name English
Fosinopril [WHO-DD]
Common Name English
FOSINOPRIL [VANDF]
Common Name English
(4S)-4-Cyclohexyl-1-[2-[(R)-[(1S)-2-methyl-1-(1-oxopropoxy)propoxy](4-phenylbutyl)phosphinyl]acetyl]-L-proline
Systematic Name English
L-Proline, 4-cyclohexyl-1-[2-[(R)-[(1S)-2-methyl-1-(1-oxopropoxy)propoxy](4-phenylbutyl)phosphinyl]acetyl]-, (4S)-
Systematic Name English
FOSINOPRIL [MI]
Common Name English
C09AA09
Code English
FOZITEC
Common Name English
FOSENOPRIL
Common Name English
Classification Tree Code System Code
NDF-RT N0000175562
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
NCI_THESAURUS C247
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
WHO-ATC C09AA09
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
NDF-RT N0000000181
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
WHO-ATC C09BA09
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
WHO-VATC QC09AA09
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
LIVERTOX NBK548813
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
WHO-VATC QC09BA09
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
Code System Code Type Description
MESH
D017328
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
CAS
98048-97-6
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
CHEBI
5163
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
LACTMED
Fosinopril
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
IUPHAR
6456
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
DRUG CENTRAL
1245
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
MERCK INDEX
m5553
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY Merck Index
WIKIPEDIA
FOSINOPRIL
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
ChEMBL
CHEMBL3039598
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
FDA UNII
R43D2573WO
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
NCI_THESAURUS
C65761
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
PUBCHEM
45357796
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
RXCUI
50166
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY RxNorm
SMS_ID
100000078508
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
DAILYMED
R43D2573WO
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
INN
5833
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
EVMPD
SUB13918MIG
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
EPA CompTox
DTXSID1023079
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
DRUG BANK
DB00492
Created by admin on Fri Dec 15 16:23:55 GMT 2023 , Edited by admin on Fri Dec 15 16:23:55 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
BINDER->LIGAND
BINDING
TRANSPORTER -> INHIBITOR
Related Record Type Details
METABOLITE ACTIVE -> PRODRUG
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC