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=C(Cl)C(Cl)=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

Molecular Formula	C35H41Cl2N3O2
Molecular Weight	606.625
Charge	0
Count

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

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 8 Target ID: CHEMBL4429 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7830490	Antagonist 2849		14.6 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Schizophrenia 305 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11757797	Primary		Phase II 1147	Unknown Approved Use Unknown
Panic disorder 24 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15706463	Primary		Phase II 1147	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	unhealthy, 34.5 Health Status: unhealthy Age Group: 34.5 Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15706463	Sources: https://pubmed.ncbi.nlm.nih.gov/15706463

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
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
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

PubMed

Title	Date	PubMed
Novel NK(3) receptor antagonists for the treatment of schizophrenia and other CNS indications.	2010-07	20597024
Pharmacological characterization of senktide-induced tail whips.	2010-01	19540857
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.	2009-11-26	19817444
Augmentation of antipsychotic-induced neurochemical changes by the NK3 receptor antagonist talnetant (SB-223412).	2009-02	18822303
The tachykinin NK3 receptor agonist senktide induces locomotor activity in male Mongolian gerbils.	2008-12-14	18930726
Me-talnetant and osanetant interact within overlapping but not identical binding pockets in the human tachykinin neurokinin 3 receptor transmembrane domains.	2008-06	18308898
Capsaicin-evoked bradycardia in anesthetized guinea pigs is mediated by endogenous tachykinins.	2008-04-10	18207255
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.	2007-03	17172464
Defensive and pathological functions of the gastrointestinal NK3 receptor.	2006-10	16901762
Neurokinin receptor antagonism attenuates cocaine's behavioural activating effects yet potentiates its dopamine-enhancing action in the nucleus accumbens core.	2006-09	17004936
Tachykinin receptors antagonists: from research to clinic.	2006-08	16918326
The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys.	2006-05-01	16603151
Selective blockade of NK2 or NK3 receptors produces anxiolytic- and antidepressant-like effects in gerbils.	2006-04	16624395
Opinion: NK3 receptor antagonists: the next generation of antipsychotics?	2005-12	16341062
Gateways to clinical trials.	2005-06	16082422
Gateways to clinical trials.	2005-04	15834452
Randomized, double-blind study of SR142801 (Osanetant). A novel neurokinin-3 (NK3) receptor antagonist in panic disorder with pre- and posttreatment cholecystokinin tetrapeptide (CCK-4) challenges.	2005-01	15706463
Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease.	2004-06-11	15190231
Gateways to clinical trials.	2004-03	15071612
SCH 206272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist.	2002-08-23	12206858
Tachykinin NK(3) receptor agonists induced microvascular leakage hypersensitivity in the guinea-pig airways.	2001-12-21	11755153
Osanetant Sanofi-Synthélabo.	2001-07	11757797
Molecular and pharmacological characterization of the murine tachykinin NK(3) receptor.	2001-02-16	11226387
Further evidence for the involvement of tachykinin receptor subtypes in formalin and capsaicin models of pain in mice.	1997-08	9308027
Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist.	1997-06	9190866
Potency and selectivity of the tachykinin NK3 receptor antagonist SR 142801.	1997-01-29	9042606
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.	1996-08-23	8702757
Two classes of structurally different antagonists display similar species preference for the human tachykinin neurokinin3 receptor.	1995-10	7476898
Functional characterization of the nonpeptide neurokinin3 (NK3) receptor antagonist, SR142801 on the human NK3 receptor expressed in Chinese hamster ovary cells.	1995-07	7616392
SR 142801, the first potent non-peptide antagonist of the tachykinin NK3 receptor.	1995	7830490

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).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:00:05 GMT 2025` Edited by `admin` on `Mon Mar 31 18:00:05 GMT 2025`
Record UNII	K7G81N94DT
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SB-236984

Preferred Name

English

OSANETANT

Official Name

English

SR142801

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