NEBENTAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H21N5O5S
Molecular Weight	491.519
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=CC=C1OC2=C(OC)N=C(N=C2NS(=O)(=O)\C=C\C3=CC=CC=C3)C4=NC=CC=N4

InChI

InChIKey=LONWRQOYFPYMQD-DTQAZKPQSA-N

InChI=1S/C24H21N5O5S/c1-32-18-11-6-7-12-19(18)34-20-21(29-35(30,31)16-13-17-9-4-3-5-10-17)27-23(28-24(20)33-2)22-25-14-8-15-26-22/h3-16H,1-2H3,(H,27,28,29)/b16-13+

HIDE SMILES / InChI

Molecular Formula	C24H21N5O5S
Molecular Weight	491.519
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18078923 | https://www.ncbi.nlm.nih.gov/pubmed/15838329 | https://www.ncbi.nlm.nih.gov/pubmed/14555186

Nebentan (YM598) is an orally active synthetic substituted phenylethenesulfonamide. As a selective endothelin A receptor antagonist, YM598 inhibits endothelin-mediated mechanisms involved in tumor cell growth and progression, angiogenesis, and metastasis. The inhibitory dissociation constant value of YM598 was 0.772 nM for native human ETA receptors, and 143 nM for native human ETB subtypes. The calculated selectivity ratio of YM598 for ETA versus ETB receptors was 222. In pithed rats, YM598 inhibited the big endothelin-1 (1 nmol/kg)-induced pressor response in a dose-dependent manner, after both intravenous and oral administration. YM598 showed not only superior antagonistic activity and higher-selectivity for endothelin ET(A) receptor in vitro, but at least a 30-fold higher potency in vivo than bosentan.

Approval Year

PubMed

Title	Date	PubMed
Pharmacological characterization of YM598, an orally active and highly potent selective endothelin ET(A) receptor antagonist.	2003 Sep 30	14555186
Effect of single oral administration of YM598, a novel selective endothelin ETA receptor antagonist, on blood pressure in normotensive and hypertensive rats.	2004 Feb	15135329
In vitro and in vivo effects of endothelin-1 and YM598, a selective endothelin ET A receptor antagonist, on the lower urinary tract.	2008 Feb 12	18078923

Patents

Sample Use Guides

In Vivo Use Guide

In the in vivo study, endothelin-1 induced the elevation of non-prostatic urethral pressure as well as prostatic urethral pressure even in the presence of tamsulosin (10 microg/kg, i.v.) in anesthetized male dogs. Nebentan (0.1-3 mg/kg, i.v.) inhibited these endothelin-1-induced contractile responses in a dose-dependent fashion.

Route of Administration: Intravenous

In Vitro Use Guide

In the in vitro study, endothelin-1 induced contractile responses in isolated rabbit bladder base, urethra, and prostate tissues. Nebentan (10(-7)-10(-5) M) antagonized endothelin-1-induced contractile responses without affecting the maximal responses. YM598 inhibited [125I]endothelin-1 binding to cloned human endothelin ET(A) and ET(B) receptor, with K(i) of 0.697 and 569 nM, and inhibited endothelin-1-induced increases in intracellular Ca(2+) concentration in human and rat endothelin ET(A) receptor. YM598 also inhibited endothelin-1-induced vasoconstriction in isolated rat aorta with a pA(2) value of 7.6.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 18:03:17 GMT 2023` Edited by `admin` on `Sat Dec 16 18:03:17 GMT 2023`
Record UNII	IJ670B0H4A
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NEBENTAN

Official Name

English

nebentan [INN]

Common Name

English

(E)-N-(6-METHOXY-5-(2-METHOXYPHENOXY)-2,2'-BIPYRIMIDIN-4-YL)-2-PHENYLETHENESULFONAMIDE

Systematic Name

English

HE-11

Code

English

Code System Code Type Description

NCI_THESAURUS

C81108