ALACEPRIL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H26N2O5S
Molecular Weight	406.496
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H](CSC(C)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC2=CC=CC=C2)C(O)=O

InChI

InChIKey=FHHHOYXPRDYHEZ-COXVUDFISA-N

InChI=1S/C20H26N2O5S/c1-13(12-28-14(2)23)19(25)22-10-6-9-17(22)18(24)21-16(20(26)27)11-15-7-4-3-5-8-15/h3-5,7-8,13,16-17H,6,9-12H2,1-2H3,(H,21,24)(H,26,27)/t13-,16+,17+/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6323222
Curator's Comment: Description was created based on several sources, including https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=NCI_Thesaurus&code=C66443

Pivalopril (RHC 3659-(S); (S)-N-cyclopentyl-N-(2-methyl-3-pivaloylthiopropionyl) glycine) is an angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Upon hydrolysis, the free SH metabolite of pivopril competitively binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This prevents the potent vasoconstrictive actions of angiotensin II and results in vasodilation. Pivopril also decreases angiotensin II-induced aldosterone secretion by the adrenal cortex, which leads to an increase in sodium excretion and subsequently increases water outflow. Pivalopril has been compared to captopril for oral angiotensin-converting enzyme (ACE) inhibition in rats and dogs and antihypertensive activity in rats. In separate groups of conscious normotensive rats, pivalopril (0.03-1.0 mg/kg, orally [p.o.]) produced a dose-related antagonism of angiotensin I (AngI)-induced pressor effects. The ED50 for pivalopriland captopril was 0.1 mg/kg. Pivalopril has being shown to be a potent, orally effective ACE inhibitor and antihypertensive agent.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Angiotensin-converting enzyme 97 Target ID: CHEMBL4074 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3009814	Inhibitor 8297		17.0 nM [IC50]
Angiotensin-converting enzyme 97 Target ID: CHEMBL1808 Sources: DOI: 10.1111/j.1527-3466.1992.tb00238.x \| https://animal.ds-pharma.co.jp/html/english/pdf/alacepriltablet_201305.pdf	Inhibitor 8297		2.9 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 567 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018343s087lbl.pdf	Primary	Approved 8429	CAPOTEN Approved Use Hypertension: CAPOTEN (captopril tablets, USP) is indicated for the treatment of hypertension. In using CAPOTEN, consideration should be given to the risk of neutropenia/agranulocytosis. CAPOTEN may be used as initial therapy for patients with normal renal function, in whom the risk is relatively low. In patients with impaired renal function, particularly those with collagen vascular disease, captopril should be reserved for hypertensives who have either developed unacceptable side effects on other drugs, or have failed to respond satisfactorily to drug combinations. CAPOTEN is effective alone and in combination with other antihypertensive agents, especially thiazide type diuretics. The blood pressure lowering effects of captopril and thiazides are approximately additive. Heart Failure: CAPOTEN is indicated in the treatment of congestive heart failure usually in combination with diuretics and digitalis. The beneficial effect of captopril in heart failure does not require the presence of digitalis, however, most controlled clinical trial experience with captopril has been in patients receiving digitalis, as well as diuretic treatment. Left Ventricular Dysfunction After Myocardial Infarction: CAPOTEN is indicated to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction manifested as an ejection fraction ≤40% and to reduce the incidence of overt heart failure and subsequent hospitalizations for congestive heart failure in these patients. Diabetic Nephropathy: CAPOTEN is indicated for the treatment of diabetic nephropathy (proteinuria >500 mg/day) in patients with type I insulin-dependent diabetes mellitus and retinopathy. CAPOTEN decreases the rate of progression of renal insufficiency and development of serious adverse clinical outcomes (death or need for renal transplantation or dialysis). Launch Date 1981
Heart Failure 7 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018343s087lbl.pdf	Primary	Approved 8429	CAPOTEN Approved Use Hypertension: CAPOTEN (captopril tablets, USP) is indicated for the treatment of hypertension. In using CAPOTEN, consideration should be given to the risk of neutropenia/agranulocytosis. CAPOTEN may be used as initial therapy for patients with normal renal function, in whom the risk is relatively low. In patients with impaired renal function, particularly those with collagen vascular disease, captopril should be reserved for hypertensives who have either developed unacceptable side effects on other drugs, or have failed to respond satisfactorily to drug combinations. CAPOTEN is effective alone and in combination with other antihypertensive agents, especially thiazide type diuretics. The blood pressure lowering effects of captopril and thiazides are approximately additive. Heart Failure: CAPOTEN is indicated in the treatment of congestive heart failure usually in combination with diuretics and digitalis. The beneficial effect of captopril in heart failure does not require the presence of digitalis, however, most controlled clinical trial experience with captopril has been in patients receiving digitalis, as well as diuretic treatment. Left Ventricular Dysfunction After Myocardial Infarction: CAPOTEN is indicated to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction manifested as an ejection fraction ≤40% and to reduce the incidence of overt heart failure and subsequent hospitalizations for congestive heart failure in these patients. Diabetic Nephropathy: CAPOTEN is indicated for the treatment of diabetic nephropathy (proteinuria >500 mg/day) in patients with type I insulin-dependent diabetes mellitus and retinopathy. CAPOTEN decreases the rate of progression of renal insufficiency and development of serious adverse clinical outcomes (death or need for renal transplantation or dialysis). Launch Date 1981
Left Ventricular Dysfunction 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018343s087lbl.pdf	Primary	Approved 8429	CAPOTEN Approved Use Hypertension: CAPOTEN (captopril tablets, USP) is indicated for the treatment of hypertension. In using CAPOTEN, consideration should be given to the risk of neutropenia/agranulocytosis. CAPOTEN may be used as initial therapy for patients with normal renal function, in whom the risk is relatively low. In patients with impaired renal function, particularly those with collagen vascular disease, captopril should be reserved for hypertensives who have either developed unacceptable side effects on other drugs, or have failed to respond satisfactorily to drug combinations. CAPOTEN is effective alone and in combination with other antihypertensive agents, especially thiazide type diuretics. The blood pressure lowering effects of captopril and thiazides are approximately additive. Heart Failure: CAPOTEN is indicated in the treatment of congestive heart failure usually in combination with diuretics and digitalis. The beneficial effect of captopril in heart failure does not require the presence of digitalis, however, most controlled clinical trial experience with captopril has been in patients receiving digitalis, as well as diuretic treatment. Left Ventricular Dysfunction After Myocardial Infarction: CAPOTEN is indicated to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction manifested as an ejection fraction ≤40% and to reduce the incidence of overt heart failure and subsequent hospitalizations for congestive heart failure in these patients. Diabetic Nephropathy: CAPOTEN is indicated for the treatment of diabetic nephropathy (proteinuria >500 mg/day) in patients with type I insulin-dependent diabetes mellitus and retinopathy. CAPOTEN decreases the rate of progression of renal insufficiency and development of serious adverse clinical outcomes (death or need for renal transplantation or dialysis). Launch Date 1981
Diabetic Nephropathy 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018343s087lbl.pdf	Primary	Approved 8429	CAPOTEN Approved Use Hypertension: CAPOTEN (captopril tablets, USP) is indicated for the treatment of hypertension. In using CAPOTEN, consideration should be given to the risk of neutropenia/agranulocytosis. CAPOTEN may be used as initial therapy for patients with normal renal function, in whom the risk is relatively low. In patients with impaired renal function, particularly those with collagen vascular disease, captopril should be reserved for hypertensives who have either developed unacceptable side effects on other drugs, or have failed to respond satisfactorily to drug combinations. CAPOTEN is effective alone and in combination with other antihypertensive agents, especially thiazide type diuretics. The blood pressure lowering effects of captopril and thiazides are approximately additive. Heart Failure: CAPOTEN is indicated in the treatment of congestive heart failure usually in combination with diuretics and digitalis. The beneficial effect of captopril in heart failure does not require the presence of digitalis, however, most controlled clinical trial experience with captopril has been in patients receiving digitalis, as well as diuretic treatment. Left Ventricular Dysfunction After Myocardial Infarction: CAPOTEN is indicated to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction manifested as an ejection fraction ≤40% and to reduce the incidence of overt heart failure and subsequent hospitalizations for congestive heart failure in these patients. Diabetic Nephropathy: CAPOTEN is indicated for the treatment of diabetic nephropathy (proteinuria >500 mg/day) in patients with type I insulin-dependent diabetes mellitus and retinopathy. CAPOTEN decreases the rate of progression of renal insufficiency and development of serious adverse clinical outcomes (death or need for renal transplantation or dialysis). Launch Date 1981
Hypertension 567 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6280740	Primary	Preclinical	Unknown Approved Use Unknown

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.9 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/3899460	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		CAPTOPRIL plasma	Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED

Doses

Dose	Population	Adverse events
50 mg 1 times / day multiple, oral Highest studied dose Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1457272	unhealthy, 54 years (range: 39-65 years) n = 10 Health Status: unhealthy Condition: essential hypertension Age Group: 54 years (range: 39-65 years) Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/1457272	Sources: https://pubmed.ncbi.nlm.nih.gov/1457272
50 mg 1 times / day multiple, oral Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10225674	unhealthy, 65 years n = 1 Health Status: unhealthy Condition: type 2 diabetes Age Group: 65 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/10225674	Disc. AE: Eruption lichenoid... AEs leading to discontinuation/dose reduction: Eruption lichenoid (severe, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/10225674

AEs

AE	Significance	Dose	Population
Eruption lichenoid	severe, 1 patient Disc. AE	50 mg 1 times / day multiple, oral Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10225674	unhealthy, 65 years n = 1 Health Status: unhealthy Condition: type 2 diabetes Age Group: 65 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/10225674

PubMed

Title	Date	PubMed
Angiotensin-converting enzyme inhibitors. New orally active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives.	1985 Jan	2981324
Spatial and temporal analysis of left ventricular filling flow propagation in hypertensive patients before and after regression of myocardial hypertrophy with alacepril therapy.	2001 Aug	11567592
Effects of the angiotensin-converting enzyme inhibitor alacepril on exercise capacity and neurohormonal factors in patients with mild-to-moderate heart failure.	2002 Dec	12390293
Effects of acute and chronic alacepril treatment on exercise capacity and hemodynamics in patients with heart failure: a preliminary study.	2002 Feb	11862975
Sialic acid 9-O-acetylesterase catalyzes the hydrolyzing reaction from alacepril to deacetylalacepril.	2003 Aug	12948030
The inhibitory effect of alacepril, an angiotensin-converting enzyme inhibitor, on endothelial inflammatory response induced by oxysterol and TNF-alpha.	2004	15720832
Long-term plasma levels and dose modulation of alacepril in patients with chronic renal failure.	2008 Jan	18360015
[Successful extubation in a patient with alacepril-induced tongue angioedema].	2010 Apr	20420150
Evaluation of the effect of an angiotensin-converting enzyme inhibitor, alacepril, on drug-induced renin-angiotensin-aldosterone system activation in normal dogs.	2016 Sep	27364087
Pharmacodynamics of alacepril in healthy cats.	2017 Jun	26927816
Effects of the angiotensin-converting enzyme inhibitor alacepril in dogs with mitral valve disease.	2018 Aug 10	29937457
Effects of high-dose alacepril on left atrial pressure and central aortic pressure in awake dogs with mitral valve regurgitation.	2019 Mar	30819428

Patents

Sample Use Guides

In Vivo Use Guide

Single oral dose (5 - 80 mg)

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

ALACEPRIL

Official Name

English

ALACEPRIL [MI]

Common Name

English

DU-1219

Code

English

N-(1-((S)-3-MERCAPTO-2-METHYLPROPIONYL)-L-PROLYL)-3-PHENYL-L-ALANINE ACETATE (ESTER)

Common Name

English

alacepril [INN]

Common Name

English

1-((2S)-3-(ACETYLTHIO)-2-METHYL-1-OXOPROPYL)-L-PROLYL-L-PHENYLALANINE

Systematic Name

English

ALACEPRIL [MART.]

Common Name

English

1-(D-3-ACETYLTHIO-2-METHYLPROPANOYL)-L-PROLYL-L-PHENYLALANINE

Common Name

English

CETAPRIL

Brand Name

English

ALACEPRIL [JAN]

Common Name

English

Alacepril [WHO-DD]

Common Name

English

NSC-338157

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C247