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

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

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 94	Inhibitor 8,504		17.0 nM [IC50]
Angiotensin-converting enzyme 94	Inhibitor 8,504		2.9 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 575	Primary	Approved 8,583	CAPOTEN
Heart Failure 7	Primary	Approved 8,583	CAPOTEN
Left Ventricular Dysfunction 4	Primary	Approved 8,583	CAPOTEN
Diabetic Nephropathy 4	Primary	Approved 8,583	CAPOTEN
Hypertension 575	Primary	Phase I 438	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
878 μg/L	100 mg single, oral		CAPTOPRIL blood	Homo sapiens
824 μg/L	100 mg 3 times / day multiple, oral		CAPTOPRIL blood	Homo sapiens
1.31 μg/mL	1 mg/kg single, oral		CAPTOPRIL plasma	Homo sapiens
800 ng/mL	100 mg single, oral		CAPTOPRIL blood	Homo sapiens
230 ng/mL	100 mg single, oral		CAPTOPRIL DISULFIDE blood	Homo sapiens
385 ng/mL	50 mg 1 times / day multiple, oral	HYDROCHLOROTHIAZIDE	CAPTOPRIL plasma	Homo sapiens
499 ng/mL	50 mg 1 times / day multiple, oral	HYDROCHLOROTHIAZIDE	CAPTOPRIL plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
1235 μg × h/L	100 mg single, oral		CAPTOPRIL blood	Homo sapiens
1197 μg × h/L	100 mg 3 times / day multiple, oral		CAPTOPRIL blood	Homo sapiens
20.1 μg × h/L/(mg dose)	2.5 mg single, intravenous		CAPTOPRIL blood	Homo sapiens
21 μg × h/L/(mg dose)	5 mg single, intravenous		CAPTOPRIL blood	Homo sapiens
20.5 μg × h/L/(mg dose)	10 mg single, intravenous		CAPTOPRIL blood	Homo sapiens
1150 ng × h/mL	100 mg single, oral		CAPTOPRIL blood	Homo sapiens
260 ng × h/mL	100 mg single, oral		CAPTOPRIL DISULFIDE blood	Homo sapiens
870 ng × h/mL	50 mg 1 times / day multiple, oral	HYDROCHLOROTHIAZIDE	CAPTOPRIL plasma	Homo sapiens
1067 ng × h/mL	50 mg 1 times / day multiple, oral	HYDROCHLOROTHIAZIDE	CAPTOPRIL plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.2 h	5 mg single, intravenous		CAPTOPRIL blood	Homo sapiens
2.1 h	10 mg single, intravenous		CAPTOPRIL blood	Homo sapiens
0.66 h	1 mg/kg single, oral		CAPTOPRIL plasma	Homo sapiens
1.9 h	50 mg single, oral		CAPTOPRIL plasma	Homo sapiens
0.83 h	50 mg 1 times / day multiple, oral	HYDROCHLOROTHIAZIDE	CAPTOPRIL plasma	Homo sapiens
0.83 h	50 mg 1 times / day multiple, oral	HYDROCHLOROTHIAZIDE	CAPTOPRIL plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
33%			CAPTOPRIL serum	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
50 mg 1 times / day multiple, oral Highest studied dose	unhealthy, 54 years (range: 39-65 years)
50 mg 1 times / day multiple, oral	unhealthy, 65 years	Disc. AE: Eruption lichenoid...
750 mg single, oral Overdose	healthy, 22	Disc. AE: Hypotension, Loss of consciousness...
500 mg single, oral Overdose	healthy, 33	Disc. AE: Hypotension, Drowsiness...
50 mg 3 times / day multiple, oral Recommended	unhealthy, 73	Disc. AE: Cough, Failure heart...

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AEs

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AE	Significance	Dose	Population
Eruption lichenoid	severe, 1 patient Disc. AE	50 mg 1 times / day multiple, oral	unhealthy, 65 years
Hypotension	Disc. AE	750 mg single, oral Overdose	healthy, 22
Loss of consciousness	Disc. AE	750 mg single, oral Overdose	healthy, 22
Drowsiness	Disc. AE	500 mg single, oral Overdose	healthy, 33
Hypotension	Disc. AE	500 mg single, oral Overdose	healthy, 33

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 620 P-gp 1,741 OAT1 725 MATE1 415 OCT2 779	OAT3 391 OAT1 395

Drug as perpetrator

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Target	Modality	Activity
MATE1 416	inhibitor 4,027	no
OCT1 656	inhibitor 4,027	no
P-gp 1,932	inhibitor 4,027	no
OAT1 730	inhibitor 4,027	yes
OCT2 782	inhibitor 4,027	yes

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
OAT1 395	substrate 4,014	yes
OAT3 391	substrate 4,014	yes

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3380	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3380
ChemicalBook	CB6206769	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6206769
eMolecules	489049	https://www.emolecules.com/cgi-bin/more?vid=489049
MolPort	MolPort-001-794-639	https://www.molport.com/shop/molecule-link/MolPort-001-794-639
Selleck Chemicals	captopril-capoten	http://www.selleckchem.com/products/captopril-capoten.html

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PubMed

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Title	Date	PubMed
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

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Patents

Sample Use Guides

In Vivo Use Guide

Single oral dose (5 - 80 mg)

Route of Administration: Oral

In Vitro Use Guide

Unknown

Show entries

Name

Type

Language

ALACEPRIL

Official Name

English

CETAPRIL

Preferred 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

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Classification Tree

Code System

Code

Antihypertensive Agent

NCI_THESAURUS

C247

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Code System

Code

Type

Description

DRUG CENTRAL

101

PRIMARY

INN

5458

PRIMARY

NCI_THESAURUS

C75021

PRIMARY

MERCK INDEX

m1463

PRIMARY

Merck Index

CAS

74258-86-9

PRIMARY

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ACTIVE MOIETY


					9G64RSX1XD

CAPTOPRIL

METABOLITE (PARENT)


					B6B1RRA3XL

DESACETYLALACEPRIL

SUBSTANCE RECORD


					X39TL7JDPF

ALACEPRIL

SMILES

InChI

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator