OSANETANT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C35H41Cl2N3O2
Molecular Weight	606.625
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(C(C)=O)C1(CCN(CCC[C@@]2(CCCN(C2)C(=O)C3=CC=CC=C3)C4=CC(Cl)=C(Cl)C=C4)CC1)C5=CC=CC=C5

InChI

InChIKey=DZOJBGLFWINFBF-UMSFTDKQSA-N

InChI=1S/C35H41Cl2N3O2/c1-27(41)38(2)35(29-13-7-4-8-14-29)19-23-39(24-20-35)21-9-17-34(30-15-16-31(36)32(37)25-30)18-10-22-40(26-34)33(42)28-11-5-3-6-12-28/h3-8,11-16,25H,9-10,17-24,26H2,1-2H3/t34-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugdevelopment-technology.com/projects/osanetant/
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/21417773

Osanetant (SR-142801) is a NK3 receptor antagonist, it has a higher affinity for human and guinea pig NK3 receptors than for rat NK3 receptors. Osanetant was under development for the treatment of schizophrenia and other Central Nervous System (CNS) disorders. It was developed by Sanofi-Aventis (formerly Sanofi-Synthelabo). Sanofi was originally investigating its potential use as a treatment for psychosis and anxiety. Following phase IIa clinical trials, osanetant entered phase IIb development in February 2001. In a review of its R&D portfolio, the company announced in August 2005 that it would cease any further development of osanetant. This follows an earlier decision to discontinue development of eplivanserin for schizophrenia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Neurokinin 3 receptor 7 Target ID: CHEMBL4429 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7830490	Antagonist 2778		14.6 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 298 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11757797	Primary		Phase II 1132	Unknown Approved Use Unknown
Panic disorder 22 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15706463	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
183 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10452109	20 mg/kg single, oral dose: 20 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		OSANETANT plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
1080 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10452109	20 mg/kg single, oral dose: 20 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		OSANETANT plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10452109	20 mg/kg single, oral dose: 20 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		OSANETANT plasma	Rattus norvegicus population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
200 mg 1 times / day multiple, oral Studied dose Dose: 200 mg, 1 times / day Route: oral Route: multiple Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/15706463 Page: p.27	unhealthy, 34.5 n = 37 Health Status: unhealthy Condition: Panic disorder Age Group: 34.5 Sex: M+F Population Size: 37 Sources: https://pubmed.ncbi.nlm.nih.gov/15706463 Page: p.27	Sources: https://pubmed.ncbi.nlm.nih.gov/15706463 Page: p.27

Sourcing

Vendor/Aggregator	ID	URL
Axon MedChem	1533	https://www.axonmedchem.com/product/1533
Chem Scene	CS-0003438	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0003438
MedChem Express	HY-14551	https://www.medchemexpress.com/search.html?q=HY-14551&ft=&fa=&fp=
MolPort	MolPort-006-170-013	https://www.molport.com/shop/molecule-link/MolPort-006-170-013
MuseChem	M040719	https://www.musechem.com/product/M040719.html
Synthonix	SL101074	http://www.synthon-lab.com/search.php?cas_or_id=SL101074&cas_id_field=1
eMolecules	260186932	https://orderbb.emolecules.com/search/#?query=260186932
eMolecules	260195090	https://orderbb.emolecules.com/search/#?query=260195090
eMolecules	300544469	https://orderbb.emolecules.com/search/#?query=300544469
eMolecules	36367138	https://orderbb.emolecules.com/search/#?query=36367138

PubMed

Title	Date	PubMed
		252160228
SR 142801, the first potent non-peptide antagonist of the tachykinin NK3 receptor.	1995	7830490
Functional characterization of the nonpeptide neurokinin3 (NK3) receptor antagonist, SR142801 on the human NK3 receptor expressed in Chinese hamster ovary cells.	1995 Jul	7616392
Two classes of structurally different antagonists display similar species preference for the human tachykinin neurokinin3 receptor.	1995 Oct	7476898
The unpredicted high affinities of a large number of naturally occurring tachykinins for chimeric NK1/NK3 receptors suggest a role for an inhibitory domain in determining receptor specificity.	1996 Aug 23	8702757
Further evidence for the involvement of tachykinin receptor subtypes in formalin and capsaicin models of pain in mice.	1997 Aug	9308027
Potency and selectivity of the tachykinin NK3 receptor antagonist SR 142801.	1997 Jan 29	9042606
Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist.	1997 Jun	9190866
Molecular and pharmacological characterization of the murine tachykinin NK(3) receptor.	2001 Feb 16	11226387
Osanetant Sanofi-Synthélabo.	2001 Jul	11757797
SCH 206272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist.	2002 Aug 23	12206858
Gateways to clinical trials.	2004 Mar	15071612
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
Defensive and pathological functions of the gastrointestinal NK3 receptor.	2006 Oct	16901762
Neurokinin-3 receptor-specific antagonists talnetant and osanetant show distinct mode of action in cellular Ca2+ mobilization but display similar binding kinetics and identical mechanism of binding in ligand cross-competition.	2007 Mar	17172464
Capsaicin-evoked bradycardia in anesthetized guinea pigs is mediated by endogenous tachykinins.	2008 Apr 10	18207255
The tachykinin NK3 receptor agonist senktide induces locomotor activity in male Mongolian gerbils.	2008 Dec 14	18930726
Me-talnetant and osanetant interact within overlapping but not identical binding pockets in the human tachykinin neurokinin 3 receptor transmembrane domains.	2008 Jun	18308898
Augmentation of antipsychotic-induced neurochemical changes by the NK3 receptor antagonist talnetant (SB-223412).	2009 Feb	18822303
Identification of a critical residue in the transmembrane domain 2 of tachykinin neurokinin 3 receptor affecting the dissociation kinetics and antagonism mode of osanetant (SR 142801) and piperidine-based structures.	2009 Nov 26	19817444
Pharmacological characterization of senktide-induced tail whips.	2010 Jan	19540857
Novel NK(3) receptor antagonists for the treatment of schizophrenia and other CNS indications.	2010 Jul	20597024

Patents

Sample Use Guides

In Vivo Use Guide

200 mg/day for a period of about 6 weeks.

Route of Administration: Oral

In Vitro Use Guide

The pharmacological profile of the novel tachykinin NK3 receptor antagonist SR 142801 was studied at tachykinin NK1, NK2 and NK3 receptors, in several in vitro bioassays. In the guinea-pig isolated ileum longitudinal muscle preparation, SR 142801 (10 nM-1 microM) caused an insurmountable antagonism of tachykinin NK3 receptor-mediated contractions produced by senktide (apparent pKB = 9.27). The blockade induced by SR 142801 was essentially irreversible, since it was not removed by washout (up to 2 h) and was increased by prolonging the incubation from 15 to 120 min. SR 142801 showed similar antagonist potency at rat tachykinin NK3 receptors (portal vein) and rabbit tachykinin NK2 receptors (pulmonary artery) (pKB = 7.49 and 7.66, respectively), whereas it was distinctly less potent at hamster tachykinin NK2 receptors (trachea; pKB = 6.84) and inactive at guinea-pig tachykinin NK1 receptors (ileum, longitudinal muscle). In the guinea-pig whole ileum SR 142801 (100 nM) did not affect the contraction produced by capsaicin (1 microM).

Name

Type

Language

OSANETANT

Official Name

English

SR142801

Code

English

SB-236984

Code

English

N-(1-(3-((R)-1-BENZOYL-3-(3,4-DICHLOROPHENYL)-3-PIPERIDYL)PROPYL)-4-PHENYL-4-PIPERIDYL)-N-METHYLACETAMIDE

Systematic Name

English

SR-142801

Code

English

osanetant [INN]

Common Name

English

SR-14280

Code

English

Code System Code Type Description

EPA CompTox

DTXSID901027521