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Identification
NameOsanetant
Accession NumberDB04872
TypeSmall Molecule
GroupsInvestigational
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
SynonymsNot Available
External Identifiers
  • SR 142801
  • SR-142801
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIK7G81N94DT
CAS number160492-56-8
WeightAverage: 606.625
Monoisotopic: 605.257582985
Chemical FormulaC35H41Cl2N3O2
InChI KeyInChIKey=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
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoyl derivatives
Direct Parent1-benzoylpiperidines
Alternative Parents
Substituents
  • 1-benzoylpiperidine
  • N-benzoylpiperidine
  • Phenylpiperidine
  • Phenylbutylamine
  • Piperidinecarboxylic acid
  • N-acyl-piperidine
  • Benzoic acid or derivatives
  • Benzamide
  • 1,2-dichlorobenzene
  • Aralkylamine
  • Halobenzene
  • Chlorobenzene
  • 4-aminopiperidine
  • Piperidine
  • Aryl halide
  • Aryl chloride
  • Acetamide
  • Tertiary carboxylic acid amide
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationPotential therapy for schizophrenia, depression and visceral pain.
PharmacodynamicsOsanetant 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 actionThe 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.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

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 of affinity of this receptor to tachykinins is: neuromedin-K > substance K > substance P.
Gene Name:
TACR3
Uniprot ID:
P29371
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 ]
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Drug created on October 20, 2007 04:46 / Updated on September 16, 2013 17:26