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Details

Stereochemistry ACHIRAL
Molecular Formula C23H21N5O5S
Molecular Weight 479.508
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AVOSENTAN

SMILES

COC1=CC=CC=C1OC2=C(NS(=O)(=O)C3=CC=C(C)C=N3)N=C(N=C2OC)C4=CC=NC=C4

InChI

InChIKey=YBWLTKFZAOSWSM-UHFFFAOYSA-N
InChI=1S/C23H21N5O5S/c1-15-8-9-19(25-14-15)34(29,30)28-22-20(33-18-7-5-4-6-17(18)31-2)23(32-3)27-21(26-22)16-10-12-24-13-11-16/h4-14H,1-3H3,(H,26,27,28)

HIDE SMILES / InChI

Molecular Formula C23H21N5O5S
Molecular Weight 479.508
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Avosentan is an oral endothelin receptor A antagonist which was developed by Roche and then licensed by Speedel (now Novartis). The drug was tested in phase III of clinical trials in patients suffering from diabetic nephropathy, however drug development was terminated due to safety reasons: avosentan caused severe heart failure and even deaths.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
19.6 ng/mL
0.5 mg 1 times / day multiple, oral
dose: 0.5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AVOSENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
1883.7 ng/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AVOSENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
228.9 ng/mL
5 mg 1 times / day multiple, oral
dose: 5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AVOSENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
54.3 ng/mL
1.5 mg 1 times / day multiple, oral
dose: 1.5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AVOSENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
247 ng × h/mL
0.5 mg 1 times / day multiple, oral
dose: 0.5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AVOSENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
15646 ng × h/mL
50 mg 1 times / day multiple, oral
dose: 50 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AVOSENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
2106 ng × h/mL
5 mg 1 times / day multiple, oral
dose: 5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AVOSENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
641 ng × h/mL
1.5 mg 1 times / day multiple, oral
dose: 1.5 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
AVOSENTAN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
PubMed

PubMed

TitleDatePubMed
Dose-dependent acute and sustained renal effects of the endothelin receptor antagonist avosentan in healthy subjects.
2009 Jun
Avosentan reduces albumin excretion in diabetics with macroalbuminuria.
2009 Mar
Unlike each drug alone, lisinopril if combined with avosentan promotes regression of renal lesions in experimental diabetes.
2009 Nov
Absolute bioavailability and pharmacokinetics of avosentan in man.
2009 Sep
Channels and transporters. Mini-symposium of the Division of Medicinal Chemistry (DMC) of the Swiss Chemical Society (SCS) at the Department of Chemistry, University of Basel, May 27, 2010.
2010
Antiatherosclerotic and renoprotective effects of ebselen in the diabetic apolipoprotein E/GPx1-double knockout mouse.
2010 Dec
The endothelin receptor antagonist avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice.
2010 Jan
Avosentan for overt diabetic nephropathy.
2010 Mar
Patents

Patents

Sample Use Guides

Oral avosentan is administered once daily at doses of 25 or 50 mg.
Route of Administration: Oral
Porcine ciliary arteries were incubated with avosentan (10(-6) M and 10(-8) M) and then exposed, cumulatively, to increasing concentrations of endothelin-1 (10(-12) M-3 × 10(-8) M). Avosentan had a strong inhibitory effect on the endothelin-1-induced contractions. The inhibitory effect of 10(-6) M avosentan was significantly stronger than the effect of 10(-8) M avosentan.
Substance Class Chemical
Created
by admin
on Fri Dec 15 17:19:53 GMT 2023
Edited
by admin
on Fri Dec 15 17:19:53 GMT 2023
Record UNII
L94KSX715K
Record Status Validated (UNII)
Record Version
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Name Type Language
AVOSENTAN
INN  
INN  
Official Name English
RO 67-0565
Code English
avosentan [INN]
Common Name English
2-PYRIDINESULFONAMIDE, N-(6-METHOXY-5-(2-METHOXYPHENOXY)-2-(4-PYRIDINYL)-4-PYRIMIDINYL)-5-METHYL-
Systematic Name English
RO-67-0565
Code English
N-(6-METHOXY-5-(2-METHOXYPHENOXY)-2-(PYRIDIN-4-YL)PYRIMIDIN-4-YL)-5-METHYLPYRIDINE-2-SULFONAMIDE
Systematic Name English
SPP-301
Code English
Code System Code Type Description
PUBCHEM
9912992
Created by admin on Fri Dec 15 17:19:53 GMT 2023 , Edited by admin on Fri Dec 15 17:19:53 GMT 2023
PRIMARY
ChEMBL
CHEMBL2107803
Created by admin on Fri Dec 15 17:19:53 GMT 2023 , Edited by admin on Fri Dec 15 17:19:53 GMT 2023
PRIMARY
MESH
C484919
Created by admin on Fri Dec 15 17:19:53 GMT 2023 , Edited by admin on Fri Dec 15 17:19:53 GMT 2023
PRIMARY
FDA UNII
L94KSX715K
Created by admin on Fri Dec 15 17:19:53 GMT 2023 , Edited by admin on Fri Dec 15 17:19:53 GMT 2023
PRIMARY
EPA CompTox
DTXSID30183330
Created by admin on Fri Dec 15 17:19:53 GMT 2023 , Edited by admin on Fri Dec 15 17:19:53 GMT 2023
PRIMARY
NCI_THESAURUS
C79485
Created by admin on Fri Dec 15 17:19:53 GMT 2023 , Edited by admin on Fri Dec 15 17:19:53 GMT 2023
PRIMARY
CAS
290815-26-8
Created by admin on Fri Dec 15 17:19:53 GMT 2023 , Edited by admin on Fri Dec 15 17:19:53 GMT 2023
PRIMARY
INN
8530
Created by admin on Fri Dec 15 17:19:53 GMT 2023 , Edited by admin on Fri Dec 15 17:19:53 GMT 2023
PRIMARY
EVMPD
SUB25426
Created by admin on Fri Dec 15 17:19:53 GMT 2023 , Edited by admin on Fri Dec 15 17:19:53 GMT 2023
PRIMARY
SMS_ID
100000089459
Created by admin on Fri Dec 15 17:19:53 GMT 2023 , Edited by admin on Fri Dec 15 17:19:53 GMT 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
Related Record Type Details
ACTIVE MOIETY