SAREDUTANT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C31H35Cl2N3O2
Molecular Weight	552.535
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C[C@@H](CCN1CCC(CC1)(NC(C)=O)C2=CC=CC=C2)C3=CC=C(Cl)C(Cl)=C3)C(=O)C4=CC=CC=C4

InChI

InChIKey=PGKXDIMONUAMFR-AREMUKBSSA-N

InChI=1S/C31H35Cl2N3O2/c1-23(37)34-31(27-11-7-4-8-12-27)16-19-36(20-17-31)18-15-26(25-13-14-28(32)29(33)21-25)22-35(2)30(38)24-9-5-3-6-10-24/h3-14,21,26H,15-20,22H2,1-2H3,(H,34,37)/t26-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C31H35Cl2N3O2
Molecular Weight	552.535
Charge	0
Count

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

Description
Sources: https://clinicaltrials.gov/ct2/show/NCT00417118 | https://www.evaluate.com/vantage/articles/analysis/sanofi-aventis-needs-successes-not-failures | https://www.ncbi.nlm.nih.gov/pubmed/11251629

Sanofi aventis developed saredutant (also known as SR 48968C) as a tachykinin neurokinin-2 (NK2) receptor antagonist for the treatment of depressive disorders and generalized anxiety disorder. This drug participated in phase III clinical trials in patients with a generalized anxiety disorder and as Combination Treatment for major depressive disorder, however, the drug failed to meet efficacy endpoints. It is known that NK-2 receptor mediates airway obstruction that is why saredutant was studied as a potential treatment of asthma. However, all studies of the drug were discontinued.

Approval Year

PubMed

Title	Date	PubMed
Influence of (+/-)-CP-96,345 and SR 48968 on electrical field stimulation of the isolated guinea-pig main bronchus.	1992 Dec 2	1334836
Characterization of the binding sites of [3H]SR 48968, a potent nonpeptide radioligand antagonist of the neurokinin-2 receptor.	1993 Mar 31	7682062
Expression of rat NK-2 (neurokinin A) receptor in E. coli.	1994	7719707
Capsaicin-induced bladder hyperactivity in normal conscious rats.	1994 Aug	7516984
'Sensory-efferent' neural control of mucus secretion: characterization using tachykinin receptor antagonists in ferret trachea in vitro.	1994 Dec	7889271
Involvement of spinal tachykinin NK1 and NK2 receptors in detrusor hyperreflexia during chemical cystitis in anaesthetized rats.	1994 Jul 1	7957606
Role of intrathecal tachykinins for micturition in unanaesthetized rats with and without bladder outlet obstruction.	1994 Sep	7812599
Prostaglandin E2-induced bladder hyperactivity in normal, conscious rats: involvement of tachykinins?	1995 Jun	7752389
Effects of neurokinin receptor antagonists on L-dopa induced bladder hyperactivity in normal conscious rats.	1995 Oct	7658588
The non-peptide tachykinin NK1- and NK2-receptor antagonists SR 140333 and SR 48968 prevent castor-oil induced diarrhea in rats.	1996	9219603
Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist.	1997 Jun	9190866
Role of tachykinins in castor oil diarrhoea in rats.	1997 Jun	9179376
Role of supraspinal tachykinins for volume- and L-dopa-induced bladder activity in normal conscious rats.	2000	10602251
Effect of a tachykinin NK(2) receptor antagonist, nepadutant, on cardiovascular and gastrointestinal function in rats and dogs.	2001 Mar 9	11245853
SCH 206272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist.	2002 Aug 23	12206858
Actions of endothelin and corticotropin releasing factor in the guinea-pig ileum: no evidence for an interaction with capsaicin-sensitive neurons.	2003 Aug	12906840
Targeting tachykinins for the treatment of obstructive airways disease.	2004	15350159
Inducible nitric oxide synthase evoked nitric oxide counteracts capsaicin-induced airway smooth muscle contraction, but exacerbates plasma extravasation.	2005 Apr 18	15774269
Antidepressant-like effects of neurokinin receptor antagonists in the forced swim test in the rat.	2005 Jan 10	15659299
Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor.	2005 Jun 1	15925360
Selective blockade of NK2 or NK3 receptors produces anxiolytic- and antidepressant-like effects in gerbils.	2006 Apr	16624395
Tachykinin receptors antagonists: from research to clinic.	2006 Aug	16918326
Role of capsaicin-sensitive afferents and sensory neuropeptides in endotoxin-induced airway inflammation and consequent bronchial hyperreactivity in the mouse.	2007 Jun 7	17291600
Capsaicin-evoked bradycardia in anesthetized guinea pigs is mediated by endogenous tachykinins.	2008 Apr 10	18207255
Occurrence and pharmacological characterization of four human tachykinin NK2 receptor variants.	2008 Aug 15	18601911
Additional evidence for anxiolytic- and antidepressant-like activities of saredutant (SR48968), an antagonist at the neurokinin-2 receptor in various rodent-models.	2008 Mar	18045668
Role of tachykinin NK(1) and NK(2) receptors in colonic sensitivity and stress-induced defecation in gerbils.	2008 Mar 17	18234189
Contractile effect of tachykinins on Suncus murinus (house musk shrew) isolated ileum.	2008 Oct-Dec	18582934
Behavioral effects of saredutant, a tachykinin NK2 receptor antagonist, in experimental models of mood disorders under basal and stress-related conditions.	2008 Sep	18495229
Multifaceted approach to determine the antagonist molecular mechanism and interaction of ibodutant ([1-(2-phenyl-1R-[[1-(tetrahydropyran-4-ylmethyl)-piperidin-4-ylmethyl]-carbamoyl]-ethylcarbamoyl)-cyclopentyl]-amide) at the human tachykinin NK2 receptor.	2009 May	19218528
Characterization of species-related differences in the pharmacology of tachykinin NK receptors 1, 2 and 3.	2009 May 1	19426690
Saredutant, an NK2 receptor antagonist, has both antidepressant-like effects and synergizes with desipramine in an animal model of depression.	2010 Aug	20470817
Involvement of sensory nerves and TRPV1 receptors in the rat airway inflammatory response to two environment pollutants: diesel exhaust particles (DEP) and 1,2-naphthoquinone (1,2-NQ).	2010 Feb	19399481
Contractile responses induced by physalaemin, an analogue of substance P, in the rat esophagus.	2010 Feb 25	19958761
Effects of intra-hippocampal injections of the NK2 receptor antagonist saredutant on the elevated plus maze, and the mouse defense test battery.	2010 Nov 26	20849917
ACS chemical neuroscience molecule spotlight on Saredutant.	2010 Oct 20	22776916
Neurokinin-1 receptor antagonist treatment in polymicrobial sepsis: molecular insights.	2010 Sep 20	21188216

Sample Use Guides

In Vivo Use Guide

Saredutant 100 mg once daily in the morning for a maximum of 8 weeks

Route of Administration: Oral

Substance Class	Chemical Created by `admin` on `Sat Dec 16 16:31:25 GMT 2023` Edited by `admin` on `Sat Dec 16 16:31:25 GMT 2023`
Record UNII	720U2QK8I5
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SAREDUTANT

Official Name

English

BENZAMIDE, N-((2S)-4-(4-(ACETYLAMINO)-4-PHENYL-1-PIPERIDINYL)-2-(3,4-DICHLOROPHENYL)BUTYL)-N-METHYL-

Systematic Name

English

saredutant [INN]

Common Name

English

SR-48968

Common Name

English

Saredutant [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C265