ECADOTRIL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H23NO4S
Molecular Weight	385.477
Optical Activity	( - )
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(=O)SC[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)OCC2=CC=CC=C2

InChI

InChIKey=ODUOJXZPIYUATO-LJQANCHMSA-N

InChI=1S/C21H23NO4S/c1-16(23)27-15-19(12-17-8-4-2-5-9-17)21(25)22-13-20(24)26-14-18-10-6-3-7-11-18/h2-11,19H,12-15H2,1H3,(H,22,25)/t19-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C21H23NO4S
Molecular Weight	385.477
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6304695 | https://www.ncbi.nlm.nih.gov/pubmed/8735864 | https://www.ncbi.nlm.nih.gov/pubmed/3481337 | https://www.ncbi.nlm.nih.gov/pubmed/22661949http://adisinsight.springer.com/drugs/800001163 | https://www.ncbi.nlm.nih.gov/pubmed/3479550

Ecadotril or sinorphan is the S-enantiomer of racemic acetorphan (racecadotril). It inhibits enkephalinase activity. Ecadotril was studied for the treatment of hypertension and heart failure, however, its development was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Angiotensin-converting enzyme 97 Target ID: CHEMBL2994 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3479550	Inhibitor 8297
Neprilysin 29 Target ID: CHEMBL2642 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3479550	Inhibitor 8297
Neprilysin 29 Target ID: CHEMBL2642 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6304695 \| https://www.ncbi.nlm.nih.gov/pubmed/7001254	Inhibitor 8297	3.5 nM [Ki]
Angiotensin-converting enzyme 97 Target ID: CHEMBL2994 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7001254 \| https://www.ncbi.nlm.nih.gov/pubmed/6304695	Inhibitor 8297	140.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Heart failure 103 Sources: http://adisinsight.springer.com/drugs/800001163	Primary	Phase II 1132	Unknown Approved Use Unknown
Pain 614 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22661949	Primary	Preclinical	Unknown Approved Use Unknown
Asthma 241 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8872633	Palliative	Phase II 1132	Unknown Approved Use Unknown
Diarrhea 35 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3481337 https://www.ncbi.nlm.nih.gov/pubmed/22661949	Primary	Preclinical	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
400 mg 2 times / day multiple, oral (max) Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10577446 Page: p.1142	unhealthy, ADULT n = 31 Health Status: unhealthy Condition: Cardiac Failure Congestive Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/10577446 Page: p.1142	Other AEs: Headache, Dizziness... Other AEs: Headache (16%) Dizziness (grade 1-2, 35%) Insomnia (6%) Sources: https://pubmed.ncbi.nlm.nih.gov/10577446 Page: p.1142

AEs

AE	Significance	Dose	Population
Headache	16%	400 mg 2 times / day multiple, oral (max) Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10577446 Page: p.1142	unhealthy, ADULT n = 31 Health Status: unhealthy Condition: Cardiac Failure Congestive Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/10577446 Page: p.1142
Insomnia	6%	400 mg 2 times / day multiple, oral (max) Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10577446 Page: p.1142	unhealthy, ADULT n = 31 Health Status: unhealthy Condition: Cardiac Failure Congestive Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/10577446 Page: p.1142
Dizziness	grade 1-2, 35%	400 mg 2 times / day multiple, oral (max) Highest studied dose Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10577446 Page: p.1142	unhealthy, ADULT n = 31 Health Status: unhealthy Condition: Cardiac Failure Congestive Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 31 Sources: https://pubmed.ncbi.nlm.nih.gov/10577446 Page: p.1142

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 activator 80 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP19A1 60 CYP2C19 1478 CYP1A2 1524

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inducer 1573 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346984#sid=144204251	inconclusive [Activation 11.2202 uM]
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743139#sid=144204251	no
CYP3A4 1925	activator 214 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/885#sid=11112861	no
CYP2C19 1553	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/899#sid=11112861	yes [IC50 0.1259 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/891#sid=11112861	yes [IC50 0.3162 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170466653	yes [IC50 0.6918 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=170466653	yes [IC50 1.2302 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/410#sid=11112861	yes [IC50 2.512 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=144204251

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY438197	https://www.001chemical.com/chem/76721-89-6
3B Scientific (Wuhan) Corp	3B3-046115	http://www.3bsc.com/index/pro_info.php?id=82714
AA Blocks	AA0035MB	https://www.aablocks.com/goods/Goods/detail?id=AA0035MB
AHH Chemical co.,ltd	MT-50654	http://www.ahhchemical.com/product/MT-50654.html
Acadechem	ACDS-070932	http://www.acadechemical.com/product/145631
Achemica	ACMC-20eo1l	http://www.achemica.com/prodinfo/?id=146524
Alfa Chemistry	AP76721896-A	https://reagents.alfa-chemistry.com/product/dl-thiorphan-cas-76721-89-6-16206.html
Alfa Chemistry	AP76721896-B	https://reagents.alfa-chemistry.com/product/dl-thiorphan-cas-76721-89-6-cas-76721-89-6-16207.html
Alichem	19139315	http://www.alichem.com/en/products/76721-89-6.html
Alsachim	668	http://www.alsachim.com/product-C2805-glo.bal-view.html
Ambinter	Amb17620621	http://www.ambinter.com/reference/17620621
Angel Pharmatech	AG202385	http://www.angelpharmatech.com/76721-89-6.html
Angene	AGN-PC-0WAFEB	http://www.angenechemical.com/productshow/AGN-PC-0WAFEB.html
Aurora Fine Chemicals LLC	A17.877.461	http://online.aurorafinechemicals.com/info?ID=A17.877.461
BLD Pharm	BD126637	http://www.bldpharm.com/products/76721-89-6.html
BOC Sciences	76721-89-6	https://aapep.bocsci.com/product/thiorphan-cas-76721-89-6-133335.html
Calbiochem	598510	http://www.emdbiosciences.com/product/598510
ChemMol	99145742	http://www.chemmol.com/chemmol/99145742.html
ChemShuttle	178241	http://www.chemshuttle.com/catalogsearch/result/?q=76721-89-6&cat=
Chemspace	CSSB00000088100	https://chem-space.com/CSSB00000088100
Clearsynth	CS-O-07004	https://www.clearsynth.com/en/CSO07004.html
Clearsynth	CS-T-44255	https://www.clearsynth.com/en/CST44255.html
Combi-Blocks	QM-5257	http://www.combi-blocks.com/cgi-bin/find.cgi?QM-5257
EMD Millipore	598510	http://www.emdbiosciences.com/product/598510
Finetech	FT-0675192	http://www.finetechnology-ind.com/prod/detail/pub/76721-89-6.html
Glentham Life Sciences	GL2922	http://www.glentham.com/products/product/GL2922/
Hairui	HR110100	http://www.hairuichem.com/en/product/76721-89-6.html
MolPort	MolPort-003-850-539	https://www.molport.com/shop/molecule-link/MolPort-003-850-539
Molcore	MC438197	https://www.molcore.com/product/76721-89-6
MuseChem	R004764	https://www.musechem.com/product/R004764.html
Nextpeptide	NP15651	http://www.nextpeptide.com/76721-89-6.html
Sigma-Aldrich	T6031_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/t6031?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S055275	http://www.sinfoobiotech.com/product/1058673
Smolecule	S591191	https://www.smolecule.com/products/s591191
THE BioTek	bt-249162	https://www.thebiotek.com/product/peptides/bt-249162
Watanabe Chemical Ind.	L00255	https://www.watanabechem.co.jp/en/search/details.php?code=L00255
abcr GmbH	AB348980	http://www.abcr.com/shop/en/AB348980
eNovation Chemicals	D583125	https://www.enovationchem.com/ProductDetails.asp?ProductID=D583125

PubMed

Title	Date	PubMed
Attenuation of the morphine withdrawal syndrome by inhibition of catabolism of endogenous enkephalins in the periaqueductal gray matter.	1992 Apr	1620246
Neutral endopeptidase (EC 3.4.24.11) in cirrhotic liver: a new target to treat portal hypertension?	2005 Nov	16085334
Synergy between natriuretic peptides and phosphodiesterase 5 inhibitors ameliorates pulmonary arterial hypertension.	2008 Oct 15	18689467
Role of mu- and delta-opioid receptors in the nucleus accumbens in cocaine-seeking behavior.	2009 Jul	19279569
A comprehensive review of the pharmacodynamics, pharmacokinetics, and clinical effects of the neutral endopeptidase inhibitor racecadotril.	2012	22661949

Patents

Sample Use Guides

In Vivo Use Guide

Mice: 300 mg/kg

Route of Administration: Intraperitoneal

In Vitro Use Guide

In saturation binding studies in various mouse tissues [3H]-thiorphan exhibited an affinity (Kd value) of 0.46–0.77 nM, and the density of [3H]-thiorphan binding sites was well correlated with measured enkephalinase activity in a panel of 11 different mouse tissues.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:52:17 GMT 2023` Edited by `admin` on `Fri Dec 15 15:52:17 GMT 2023`
Record UNII	6XSR933SRK
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ECADOTRIL

Official Name

English

BAY Y 7432

Code

English

BAY-Y-7432

Code

English

ECADOTRIL [USAN]

Common Name

English

N-[(S)-α-(Mercaptomethyl)hydrocinnamoyl]glycine, benzyl ester, acetate (ester)

Common Name

English

ecadotril [INN]

Common Name

English

GLYCINE, N-(2-((ACETYLTHIO)METHYL)-1-OXO-3-PHENYLPROPYL)-, PHENYLMETHYL ESTER, (S)-

Common Name

English

Sinorphan

Common Name

English

S-049

Code

English

RACECADOTRIL (S)-FORM [MI]

Common Name

English

RACECADOTRIL (S)-FORM

Common Name

English

BP 1.02

Code

English

S049

Code

English

BP-1.02

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C783