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
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
Molecular Formula | C20H26N2O5S |
Molecular Weight | 406.496 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/6323222Curator'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
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 |
---|---|---|---|
Target ID: CHEMBL4074 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3009814 |
17.0 nM [IC50] | ||
Target ID: CHEMBL1808 |
2.9 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | CAPOTEN Approved UseHypertension: 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 Date1981 |
|||
Primary | CAPOTEN Approved UseHypertension: 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 Date1981 |
|||
Primary | CAPOTEN Approved UseHypertension: 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 Date1981 |
|||
Primary | CAPOTEN Approved UseHypertension: 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 Date1981 |
|||
Primary | Unknown Approved UseUnknown |
T1/2
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: |
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: |
|
50 mg 1 times / day multiple, oral Dose: 50 mg, 1 times / day Route: oral Route: multiple Dose: 50 mg, 1 times / day Sources: |
unhealthy, 65 years n = 1 Health Status: unhealthy Condition: type 2 diabetes Age Group: 65 years Sex: F Population Size: 1 Sources: |
Disc. AE: Eruption lichenoid... AEs leading to discontinuation/dose reduction: Eruption lichenoid (severe, 1 patient) Sources: |
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: |
unhealthy, 65 years n = 1 Health Status: unhealthy Condition: type 2 diabetes Age Group: 65 years Sex: F Population Size: 1 Sources: |
PubMed
Title | Date | PubMed |
---|---|---|
Angiotensin-converting enzyme inhibitors. New orally active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives. | 1985 Jan |
|
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 |
|
Effects of the angiotensin-converting enzyme inhibitor alacepril on exercise capacity and neurohormonal factors in patients with mild-to-moderate heart failure. | 2002 Dec |
|
Effects of acute and chronic alacepril treatment on exercise capacity and hemodynamics in patients with heart failure: a preliminary study. | 2002 Feb |
|
Sialic acid 9-O-acetylesterase catalyzes the hydrolyzing reaction from alacepril to deacetylalacepril. | 2003 Aug |
|
The inhibitory effect of alacepril, an angiotensin-converting enzyme inhibitor, on endothelial inflammatory response induced by oxysterol and TNF-alpha. | 2004 |
|
Long-term plasma levels and dose modulation of alacepril in patients with chronic renal failure. | 2008 Jan |
|
[Successful extubation in a patient with alacepril-induced tongue angioedema]. | 2010 Apr |
|
Evaluation of the effect of an angiotensin-converting enzyme inhibitor, alacepril, on drug-induced renin-angiotensin-aldosterone system activation in normal dogs. | 2016 Sep |
|
Pharmacodynamics of alacepril in healthy cats. | 2017 Jun |
|
Effects of the angiotensin-converting enzyme inhibitor alacepril in dogs with mitral valve disease. | 2018 Aug 10 |
|
Effects of high-dose alacepril on left atrial pressure and central aortic pressure in awake dogs with mitral valve regurgitation. | 2019 Mar |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6280740
Single oral dose (5 - 80 mg)
Route of Administration:
Oral
Substance Class |
Chemical
Created
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admin
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Record UNII |
X39TL7JDPF
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Validated (UNII)
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C247
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ACTIVE MOIETY |