Osanetant

Identification

Name
Osanetant
Accession Number
DB04872
Type
Small Molecule
Groups
Investigational
Description

Developed by Sanofi-Aventis (formerly Sanofi-Synthelabo), osanetant (SR-142801) is an NK3 receptor antagonist which was under development for the treatment of schizophrenia and other Central Nervous System (CNS) disorders. 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.

Structure
Thumb
Synonyms
Not Available
External IDs
SR 142801 / SR-142801 / SR142801
Categories
UNII
K7G81N94DT
CAS number
160492-56-8
Weight
Average: 606.625
Monoisotopic: 605.257582985
Chemical Formula
C35H41Cl2N3O2
InChI Key
DZOJBGLFWINFBF-UMSFTDKQSA-N
InChI
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
IUPAC Name
N-(1-{3-[(3R)-1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl]propyl}-4-phenylpiperidin-4-yl)-N-methylacetamide
SMILES
CN(C(C)=O)C1(CCN(CCC[C@@]2(CCCN(C2)C(=O)C2=CC=CC=C2)C2=CC(Cl)=C(Cl)C=C2)CC1)C1=CC=CC=C1

Pharmacology

Indication

Potential therapy for schizophrenia, depression and visceral pain.

Pharmacodynamics

Osanetant is a neurokinin-3 (NK3) receptor antagonist. Preliminary clinical trials have demonstrated that osanetant is superior to placebo on global assessment of efficacy and measures of positive symptoms in schizophrenia.

Mechanism of action

The mechanism of action of osanetant is uncertain at this point. Various preclinical data indicate that activation of NK3 receptors enhances the release of biogenic amines, including dopamine and serotonin. NK3 receptor antagonists could block NK3-receptor-mediated activation of these systems.

TargetActionsOrganism
UNeuromedin-K receptorNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,5-Dimethoxy-4-ethylamphetamineOsanetant may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineOsanetant may decrease the stimulatory activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineOsanetant may decrease the stimulatory activities of 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineOsanetant may decrease the stimulatory activities of 4-Bromo-2,5-dimethoxyamphetamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when 7-Nitroindazole is combined with Osanetant.
AcepromazineThe risk or severity of adverse effects can be increased when Acepromazine is combined with Osanetant.
AceprometazineThe risk or severity of adverse effects can be increased when Aceprometazine is combined with Osanetant.
AdipiplonThe risk or severity of adverse effects can be increased when Osanetant is combined with Adipiplon.
AgomelatineThe risk or severity of adverse effects can be increased when Osanetant is combined with Agomelatine.
AlaproclateThe risk or severity of adverse effects can be increased when Osanetant is combined with Alaproclate.
Food Interactions
Not Available

References

General References
  1. Kronenberg G, Berger P, Tauber RF, Bandelow B, Henkel V, Heuser I: 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. Pharmacopsychiatry. 2005 Jan;38(1):24-9. [PubMed:15706463]
  2. Kamali F: Osanetant Sanofi-Synthelabo. Curr Opin Investig Drugs. 2001 Jul;2(7):950-6. [PubMed:11757797]
External Links
PubChem Compound
219077
PubChem Substance
175426879
ChemSpider
189901
BindingDB
50291261
ChEMBL
CHEMBL346178
Wikipedia
Osanetant

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000154 mg/mLALOGPS
logP6.47ALOGPS
logP6.27ChemAxon
logS-6.6ALOGPS
pKa (Strongest Basic)9.3ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area43.86 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity172.73 m3·mol-1ChemAxon
Polarizability66.11 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9486
Blood Brain Barrier+0.9882
Caco-2 permeable+0.5767
P-glycoprotein substrateSubstrate0.6866
P-glycoprotein inhibitor IInhibitor0.7694
P-glycoprotein inhibitor IIInhibitor0.837
Renal organic cation transporterInhibitor0.5525
CYP450 2C9 substrateNon-substrate0.8013
CYP450 2D6 substrateNon-substrate0.6861
CYP450 3A4 substrateSubstrate0.7427
CYP450 1A2 substrateNon-inhibitor0.9532
CYP450 2C9 inhibitorNon-inhibitor0.9439
CYP450 2D6 inhibitorInhibitor0.5109
CYP450 2C19 inhibitorNon-inhibitor0.8248
CYP450 3A4 inhibitorNon-inhibitor0.703
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7353
Ames testNon AMES toxic0.7977
CarcinogenicityNon-carcinogens0.8292
BiodegradationNot ready biodegradable0.994
Rat acute toxicity2.8030 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9523
hERG inhibition (predictor II)Inhibitor0.8584
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 1-benzoylpiperidines. These are compounds containing a piperidine ring substituted at the 1-position with a benzoyl group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzoyl derivatives
Direct Parent
1-benzoylpiperidines
Alternative Parents
N-benzoylpiperidines / Phenylpiperidines / Phenylbutylamines / Benzamides / Dichlorobenzenes / Aralkylamines / Aryl chlorides / Tertiary carboxylic acid amides / Acetamides / Trialkylamines
show 7 more
Substituents
N-benzoylpiperidine / 1-benzoylpiperidine / Phenylpiperidine / Phenylbutylamine / N-acyl-piperidine / Benzamide / Benzoic acid or derivatives / 1,2-dichlorobenzene / Aralkylamine / Chlorobenzene
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Details
1. Neuromedin-K receptor
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Tachykinin receptor activity
Specific Function
This is a receptor for the tachykinin neuropeptide neuromedin-K (neurokinin B). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order...
Gene Name
TACR3
Uniprot ID
P29371
Uniprot Name
Neuromedin-K receptor
Molecular Weight
52201.35 Da
References
  1. Tian G, Wilkins D, Scott CW: 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. Mol Pharmacol. 2007 Mar;71(3):902-11. Epub 2006 Dec 15. [PubMed:17172464]

Drug created on October 20, 2007 04:46 / Updated on August 02, 2018 05:27