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
- 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.
Target Actions Organism UNeuromedin-K receptor Not Available Humans - 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
Drug Interaction Ajulemic acid The risk or severity of adverse effects can be increased when Ajulemic acid is combined with Osanetant. Alaproclate The risk or severity of adverse effects can be increased when Osanetant is combined with Alaproclate. Amineptine The risk or severity of adverse effects can be increased when Amineptine is combined with Osanetant. Amitriptylinoxide Osanetant may increase the neurotoxic activities of Amitriptylinoxide. Amperozide The risk or severity of adverse effects can be increased when Osanetant is combined with Amperozide. Aripiprazole lauroxil The risk or severity of adverse effects can be increased when Osanetant is combined with Aripiprazole lauroxil. Bismuth subcarbonate Osanetant may increase the neurotoxic activities of Bismuth subcarbonate. Bismuth subcitrate potassium Osanetant may increase the neurotoxic activities of Bismuth subcitrate potassium. Bismuth subgallate Osanetant may increase the neurotoxic activities of Bismuth subgallate. Bismuth subnitrate Osanetant may increase the neurotoxic activities of Bismuth subnitrate. - Food Interactions
- Not Available
References
- General References
- 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]
- Kamali F: Osanetant Sanofi-Synthelabo. Curr Opin Investig Drugs. 2001 Jul;2(7):950-6. [PubMed:11757797]
- External Links
Clinical Trials
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
Property Value Source Water Solubility 0.000154 mg/mL ALOGPS logP 6.47 ALOGPS logP 6.27 ChemAxon logS -6.6 ALOGPS pKa (Strongest Basic) 9.3 ChemAxon Physiological Charge 1 ChemAxon Hydrogen Acceptor Count 3 ChemAxon Hydrogen Donor Count 0 ChemAxon Polar Surface Area 43.86 Å2 ChemAxon Rotatable Bond Count 8 ChemAxon Refractivity 172.73 m3·mol-1 ChemAxon Polarizability 66.11 Å3 ChemAxon Number of Rings 5 ChemAxon Bioavailability 0 ChemAxon Rule of Five No ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule Yes ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9486 Blood Brain Barrier + 0.9882 Caco-2 permeable + 0.5767 P-glycoprotein substrate Substrate 0.6866 P-glycoprotein inhibitor I Inhibitor 0.7694 P-glycoprotein inhibitor II Inhibitor 0.837 Renal organic cation transporter Inhibitor 0.5525 CYP450 2C9 substrate Non-substrate 0.8013 CYP450 2D6 substrate Non-substrate 0.6861 CYP450 3A4 substrate Substrate 0.7427 CYP450 1A2 substrate Non-inhibitor 0.9532 CYP450 2C9 inhibitor Non-inhibitor 0.9439 CYP450 2D6 inhibitor Inhibitor 0.5109 CYP450 2C19 inhibitor Non-inhibitor 0.8248 CYP450 3A4 inhibitor Non-inhibitor 0.703 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7353 Ames test Non AMES toxic 0.7977 Carcinogenicity Non-carcinogens 0.8292 Biodegradation Not ready biodegradable 0.994 Rat acute toxicity 2.8030 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9523 hERG inhibition (predictor II) Inhibitor 0.8584
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not 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
- Kind
- Protein
- Organism
- Humans
- 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
- 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 November 02, 2018 06:06