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Rimonabant

July 24, 2017
Common Name

Rimonabant Description

Rimonabant is an anorectic anti-obesity drug produced and marketed by Sanofi-Aventis. It is an inverse agonist for the cannabinoid receptor CB1. Its main avenue of effect is reduction in appetite. Rimonabant is the first selective CB1 receptor blocker to be approved for use anywhere in the world. Rimonabant is approved in 38 countries including the E.U., Mexico, and Brazil. It was rejected for approval for use in the United States. This decision was made after a U.S. advisory panel recommended the medicine not be approved because it may increase suicidal thinking and depression. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source AcompliaKegg SR 141716HMDB SR 141716aHMDB SR141716HMDB SR141716aHMDB N-(Piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochlorideMeSH ZimlitiMeSH

Chemical Formlia

C22H21Cl3N4O Average Molecliar Weight

463.787 Monoisotopic Molecliar Weight

462.078094435 IUPAC Name

5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide Traditional Name

rimonabant CAS Registry Number

158681-13-1 SMILES

CC1=C(N(N=C1C(=O)NN1CCCCC1)C1=C(Cl)C=C(Cl)C=C1)C1=CC=C(Cl)C=C1

InChI Identifier

InChI=1S/C22H21Cl3N4O/c1-14-20(22(30)27-28-11-3-2-4-12-28)26-29(19-10-9-17(24)13-18(19)25)21(14)15-5-7-16(23)8-6-15/h5-10,13H,2-4,11-12H2,1H3,(H,27,30)

InChI Key

JZCPYUJPEARBJL-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as phenylpyrazoles. These are compounds containing a phenylpyrazole skeleton, which consists of a pyrazole bound to a phenyl group. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Azoles Direct Parent

Phenylpyrazoles Alternative Parents

  • Dichlorobenzenes
  • Piperidines
  • Aryl chlorides
  • Heteroaromatic compounds
  • Hydrazones
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organooxygen compounds
  • Organochlorides
  • Hydrocarbon derivatives

    • Substituents

  • Phenylpyrazole
  • 1,3-dichlorobenzene
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • Monocyclic benzene moiety
  • Benzenoid
  • Piperidine
  • Heteroaromatic compound
  • Azacycle
  • Hydrazone
  • Organohalogen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Organochloride
  • Organonitrogen compound
  • Aromatic heteromonocyclic compound

    • Molecliar Framework

    Aromatic heteromonocyclic compounds External Descriptors

  • pyrazoles (CHEBI:34967 )
  • ring assembly (CHEBI:34967 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-Obesity Agents

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility2.00e-03 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.002 mg/mLALOGPS logP5.47ALOGPS logP5.91ChemAxon logS-5.4ALOGPS pKa (Strongest Acidic)12.42ChemAxon pKa (Strongest Basic)1.68ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count3ChemAxon Hydrogen Donor Count1ChemAxon Polar Surface Area50.16 Å2ChemAxon Rotatable Bond Count4ChemAxon Refractivity122.83 m3·mol-1ChemAxon Polarizability47.96 Å3ChemAxon Number of Rings4ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key LC-MS/MS

    LC-MS/MS Spectrum – , positivesplash10-03xr-0007900000-a3e664246f26a3081b28View in MoNA Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

    Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

    Biological Properties Cellliar Locations

  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06155

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB06155

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB06155 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    94641 KEGG Compound ID

    C14319 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Rimonabant NuGOwiki Link

    HMDB15623 Metagene Link

    HMDB15623 METLIN ID

    Not Available PubChem Compound

    104850 PDB ID

    Not Available ChEBI ID

    116088

    Product: Sulfathiazole

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, Frank RA: Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry. 2001 Apr;58(4):322-8. [PubMed:11296091 ]
    2. Maldonado R, Valverde O, Berrendero F: Involvement of the endocannabinoid system in drug addiction. Trends Neurosci. 2006 Apr;29(4):225-32. Epub 2006 Feb 17. [PubMed:16483675 ]
    3. Gelfand EV, Cannon CP: Rimonabant: a selective blocker of the cannabinoid CB1 receptors for the management of obesity, smoking cessation and cardiometabolic risk factors. Expert Opin Investig Drugs. 2006 Mar;15(3):307-15. [PubMed:16503766 ]
    4. Xie S, Furjanic MA, Ferrara JJ, McAndrew NR, Ardino EL, Ngondara A, Bernstein Y, Thomas KJ, Kim E, Walker JM, Nagar S, Ward SJ, Raffa RB: The endocannabinoid system and rimonabant: a new drug with a novel mechanism of action involving cannabinoid CB1 receptor antagonism–or inverse agonism–as potential obesity treatment and other therapeutic use. J Clin Pharm Ther. 2007 Jun;32(3):209-31. [PubMed:17489873 ]
    5. Deadwyler SA, Goonawardena AV, Hampson RE: Short-term memory is modulated by the spontaneous release of endocannabinoids: evidence from hippocampal population codes. Behav Pharmacol. 2007 Sep;18(5-6):571-80. [PubMed:17762525 ]
    6. Cahill K, Ussher M: Cannabinoid type 1 receptor antagonists (rimonabant) for smoking cessation. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005353. [PubMed:17943852 ]

    Enzymes

    General function:
    Involved in monooxygenase activity
    Specific function:
    Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    References
    1. Leite CE, Mocelin CA, Petersen GO, Leal MB, Thiesen FV: Rimonabant: an antagonist drug of the endocannabinoid system for the treatment of obesity. Pharmacol Rep. 2009 Mar-Apr;61(2):217-24. [PubMed:19443932 ]
    2. Lazary J, Juhasz G, Hunyady L, Bagdy G: Personalized medicine can pave the way for the safe use of CB(1) receptor antagonists. Trends Pharmacol Sci. 2011 May;32(5):270-80. doi: 10.1016/j.tips.2011.02.013. Epub 2011 Apr 16. [PubMed:21497918 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    Involved in cannabinoid-induced CNS effects. Acts by inhibiting adenylate cyclase. Could be a receptor for anandamide. Inhibits L-type Ca(2+) channel current. Isoform 2 and isoform 3 have altered ligand binding
    Gene Name:
    CNR1
    Uniprot ID:
    P21554
    Molecular weight:
    52857.4
    References
    1. Shire D, Calandra B, Delpech M, Dumont X, Kaghad M, Le Fur G, Caput D, Ferrara P: Structural features of the central cannabinoid CB1 receptor involved in the binding of the specific CB1 antagonist SR 141716A. J Biol Chem. 1996 Mar 22;271(12):6941-6. [PubMed:8636122 ]
    2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

    PMID: 17652633

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