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

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
A potent and selective non-peptide antagonist of the neurokinin A (NK2) receptor.	1992	1313515
Characterization of the capsaicin-sensitive component of cyclophosphamide-induced inflammation in the rat urinary bladder.	1994 Apr	8032584
'Sensory-efferent' neural control of mucus secretion: characterization using tachykinin receptor antagonists in ferret trachea in vitro.	1994 Dec	7889271
The non-peptide tachykinin NK2 receptor antagonist SR 48968 interacts with human, but not rat, cloned tachykinin NK3 receptors.	1994 Feb 15	8117304
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
Further evidence for the involvement of tachykinin receptor subtypes in formalin and capsaicin models of pain in mice.	1997 Aug	9308027
Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist.	1997 Jun	9190866
Effect of tachykinin receptor antagonists in experimental neuropathic pain.	1998 Nov 20	9865506
Acetylcholine and tachykinin receptor antagonists attenuate wood smoke-induced bronchoconstriction in guinea pigs.	1998 Nov 6	9851584
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
Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor.	2005 Jun 1	15925360
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
Contractile responses induced by physalaemin, an analogue of substance P, in the rat esophagus.	2010 Feb 25	19958761
ACS chemical neuroscience molecule spotlight on Saredutant.	2010 Oct 20	22776916

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

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