FOSINOPRIL

First approved in 1991

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 Search

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
Sources: http://www.drugbank.ca/drugs/DB00492
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Angiotensin-converting enzyme 97 Target ID: CHEMBL1808 Sources: http://www.drugbank.ca/drugs/DB00492	Inhibitor 8297		1.0 nM [IC50]
Angiotensin-converting enzyme 97 Target ID: P12822 Gene ID: 1.00009272E8 Gene Symbol: ACE Target Organism: Oryctolagus cuniculus (Rabbit) Sources: https://www.ncbi.nlm.nih.gov/pubmed/2481187	Inhibitor 8297		11.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: https://www.drugs.com/pro/fosinopril.html	Primary		Approved 8429	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

C_max

Value	Dose	Analyte	Population
1556 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2967089/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2967089/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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

Value	Dose	Analyte	Population
3302 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2967089/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2967089/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1646240/	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2967089/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2967089/	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2967089/	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% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2967089/	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/1534664/	unhealthy, 28 - 68years n = 12 Health Status: unhealthy Condition: essential hypertension Age Group: 28 - 68years Sex: M+F Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/1534664/	Sources: https://pubmed.ncbi.nlm.nih.gov/1534664/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf Page: 16	unhealthy, >65 years n = 688 Health Status: unhealthy Condition: hypertension Age Group: >65 years Sex: unknown Population Size: 688 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf 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: https://www.rxlist.com/monopril-drug.htm#description	unhealthy, adult Health Status: unhealthy Condition: hypertension Age Group: adult Sex: unknown Sources: https://www.rxlist.com/monopril-drug.htm#description	Sources: https://www.rxlist.com/monopril-drug.htm#description

AEs

AE	Significance	Dose	Population
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf Page: 16	unhealthy, >65 years n = 688 Health Status: unhealthy Condition: hypertension Age Group: >65 years Sex: unknown Population Size: 688 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf Page: 16	unhealthy, >65 years n = 688 Health Status: unhealthy Condition: hypertension Age Group: >65 years Sex: unknown Population Size: 688 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf Page: 16	unhealthy, >65 years n = 688 Health Status: unhealthy Condition: hypertension Age Group: >65 years Sex: unknown Population Size: 688 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf Page: 16	unhealthy, >65 years n = 688 Health Status: unhealthy Condition: hypertension Age Group: >65 years Sex: unknown Population Size: 688 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/19915se5-037_monopril_lbl.pdf Page: 16

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2B6 810 P-gp 1461 BCRP 699 MRP2 383	CYP1A1 349 CYP1A2 1054 CYP2B1 12 CYP2B2 3 CYP2E1 667 CYP3A 191 UGT 192 PEPT1 49

Drug as perpetrator

Target	Modality	Activity
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17101742/	no
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23262422/	yes
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23262422/	yes
P-gp 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23262422/	yes

Drug as victim

Target	Modality	Activity
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20692951/	no
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20692951/	no
CYP2B1 12	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20692951/	no
CYP2B2 3	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20692951/	no
CYP2E1 667	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20692951/	no
PEPT1 49	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11560874/	yes [Km 154 uM]
CYP3A 191	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24365260/	yes
UGT 192	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24365260/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:116962	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:116962
ChemicalBook	CB4711162	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4711162
ZINC	ZINC000004213382	http://zinc15.docking.org/substances/ZINC000004213382

PubMed

Title	Date	PubMed
The hemodynamic effects of long-term ACE inhibition with fosinopril in patients with heart failure. Fosinopril Hemodynamics Study Group.	1999 Jul	11329095
Elevation of serum creatinine following fosinopril therapy.	1999 Mar	10200870
Effect of valsartan and fosinopril on catecholamine-induced cardiac hypertrophy.	2000 Sep	11501170
[Effects of lorsartan, fosinopril on myocardial fibrosis, angiotensin II and cardiac remolding in hypertensive rats].	2001 Apr 28	12536639
Endogenous natriuretic peptides participate in renal and humoral actions of acute vasopeptidase inhibition in experimental mild heart failure.	2001 Aug	11509474
ACE inhibitor-induced angioedema of the intestine: Case report, incidence, pathophysiology, diagnosis and management.	2001 Dec	11773949
Diverse effects of chronic treatment with losartan, fosinopril, and amlodipine on apoptosis, angiotensin II in the left ventricle of hypertensive rats.	2001 Dec	11744126
Effects of fosinopril on renal function, baroreflex response and noradrenaline pressor response in conscious normotensive dogs.	2001 Jul	11469507
Fenofibrate and warfarin interaction.	2001 Jul	11444587
The effects of ACE inhibitor therapy on left ventricular myocardial mass and diastolic filling in previously untreated hypertensive patients: a cine MRI study.	2001 Jul	11436209
Pharmacoutilization of antihypertensive drugs: a model of analysis.	2001 Jun	11430633
Mechanism of intestinal absorption and renal reabsorption of an orally active ace inhibitor: uptake and transport of fosinopril in cell cultures.	2001 Oct	11560874
Rapid determination of partition coefficients between n-octanol/water for cardiovascular therapies.	2002 Jan-Feb	11782815
[Renoprotective effect of monopril in patients with diabetes mellitus in the preclinical stage of diabetic nephropathy].	2002 Jul-Sep	12442535
The effects of losartan and fosinopril in hypertensive type 2 diabetic patients.	2002 Oct	12161053
Gateways to Clinical Trials.	2002 Sep	12428432
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	14573331
Angiotensin-converting enzyme inhibition but not angiotensin II receptor blockade regulates matrix metalloproteinase activity in patients with glomerulonephritis.	2003 Nov	14569096
Ramipril-associated hepatotoxicity.	2003 Nov	14567716
Protection of organic trauma in sinoaortic-denervated rats treated with fosinopril.	2003 Oct	14730896
Introduction to monitoring. What is what you prescribed actually doing?	2003 Oct	14596082
Dual renin-angiotensin system blockade restores blood pressure-renin dependency in individuals with low renin concentrations.	2003 Oct	14508195
[Effect of fosinopril on the rate of neurohumoral and proinflammatory activation in patients with heart failure].	2004	15540418
Heart failure and first dose hypotension after angiotensin converting enzyme inhibitors.	2004 Dec	15744357
[Changes of collagen expression of pulmonary arteries and heart ventricles and intervention of fosinopril and losartan in rats with heart failure].	2004 Dec 2	15730820
Cardiorenal protective effects of vasopeptidase inhibition with omapatrilat in hypertensive transgenic (mREN-2)27 rats.	2004 Jan	15000298
Role of Angiotensin-converting enzyme and neutral endopeptidase in flow-dependent remodeling.	2004 Mar-Apr	15004434
Framingham score and microalbuminuria: combined future targets for primary prevention?	2004 Nov	15485402
Lumbar incisional hernias: diagnostic and management dilemma.	2004 Oct-Dec	15554289
Lithium toxicity after switch from fosinopril to lisinopril.	2005 Mar	15729089
Effects of fosinopril and pravastatin on carotid intima-media thickness in subjects with increased albuminuria.	2005 Mar	15692120

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

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Name

Type

Language

FOSINOPRIL

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