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
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
DescriptionCurator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/21417773
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.
Originator
Approval Year
Cmax
| 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 |
T1/2
| 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: 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: Page: p.27 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| SR 142801, the first potent non-peptide antagonist of the tachykinin NK3 receptor. | 1995 |
|
| Functional characterization of the nonpeptide neurokinin3 (NK3) receptor antagonist, SR142801 on the human NK3 receptor expressed in Chinese hamster ovary cells. | 1995 Jul |
|
| Two classes of structurally different antagonists display similar species preference for the human tachykinin neurokinin3 receptor. | 1995 Oct |
|
| 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 |
|
| Further evidence for the involvement of tachykinin receptor subtypes in formalin and capsaicin models of pain in mice. | 1997 Aug |
|
| Potency and selectivity of the tachykinin NK3 receptor antagonist SR 142801. | 1997 Jan 29 |
|
| Nonpeptide tachykinin receptor antagonists: I. Pharmacological and pharmacokinetic characterization of SB 223412, a novel, potent and selective neurokinin-3 receptor antagonist. | 1997 Jun |
|
| Tachykinin NK(3) receptor agonists induced microvascular leakage hypersensitivity in the guinea-pig airways. | 2001 Dec 21 |
|
| Molecular and pharmacological characterization of the murine tachykinin NK(3) receptor. | 2001 Feb 16 |
|
| Osanetant Sanofi-Synthélabo. | 2001 Jul |
|
| SCH 206272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist. | 2002 Aug 23 |
|
| Gateways to clinical trials. | 2004 Mar |
|
| Neurokinin B, neurotensin, and cannabinoid receptor antagonists and Parkinson disease. | 2004 May-Jun |
|
| Gateways to clinical trials. | 2005 Apr |
|
| Opinion: NK3 receptor antagonists: the next generation of antipsychotics? | 2005 Dec |
|
| 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 Jan |
|
| Gateways to clinical trials. | 2005 Jun |
|
| Selective blockade of NK2 or NK3 receptors produces anxiolytic- and antidepressant-like effects in gerbils. | 2006 Apr |
|
| Tachykinin receptors antagonists: from research to clinic. | 2006 Aug |
|
| The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys. | 2006 May 1 |
|
| Defensive and pathological functions of the gastrointestinal NK3 receptor. | 2006 Oct |
|
| Neurokinin receptor antagonism attenuates cocaine's behavioural activating effects yet potentiates its dopamine-enhancing action in the nucleus accumbens core. | 2006 Sep |
|
| 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 |
|
| Capsaicin-evoked bradycardia in anesthetized guinea pigs is mediated by endogenous tachykinins. | 2008 Apr 10 |
|
| The tachykinin NK3 receptor agonist senktide induces locomotor activity in male Mongolian gerbils. | 2008 Dec 14 |
|
| Me-talnetant and osanetant interact within overlapping but not identical binding pockets in the human tachykinin neurokinin 3 receptor transmembrane domains. | 2008 Jun |
|
| Augmentation of antipsychotic-induced neurochemical changes by the NK3 receptor antagonist talnetant (SB-223412). | 2009 Feb |
|
| 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 |
|
| Pharmacological characterization of senktide-induced tail whips. | 2010 Jan |
|
| Novel NK(3) receptor antagonists for the treatment of schizophrenia and other CNS indications. | 2010 Jul |
Patents
Sample Use Guides
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).
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DTXSID901027521
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DB04872
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OSANETANT
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160492-56-8
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C170264
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100000083352
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K7G81N94DT
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ACTIVE MOIETY
