Posted inUncategorized

Solifenacin

July 24, 2017
Common Name

Solifenacin Description

Solifenacin is only found in individuals that have used or taken this drug. It is a urinary antispasmodic of the anticholinergic class. It is used in the treatment of overactive bladder with urge incontinence. [Wikipedia]Solifenacin is a competitive muscarinic acetylcholine receptor antagonist. The binding of acetylcholine to these receptors, particliarly the M3 receptor subtype, plays a critical role in the contraction of smooth muscle. By preventing the binding of acetylcholine to these receptors, solifenacin reduces smooth muscle tone in the bladder, allowing the bladder to retain larger volumes of urine and reducing the number of incontinence episodes. Structure

MOLSDFPDBSMILESInChI

Synonyms

Value Source YM-905vesicareChEMBL Solifenacin succinateHMDB 905, YMMeSH Succinate, solifenacinMeSH Quinuclidin-3'-yl-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinateMeSH VesicareMeSH

Chemical Formlia

C27H32N2O6 Average Molecliar Weight

480.5528 Monoisotopic Molecliar Weight

480.226036766 IUPAC Name

(3R)-1-azabicyclo[2.2.2]octan-3-yl (1S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate; butanedioic acid Traditional Name

solifenacin; succinic acid CAS Registry Number

242478-37-1 SMILES

OC(=O)CCC(O)=O.O=C(O[C@H]1CN2CCC1CC2)N1CCC2=CC=CC=C2[C@@H]1C1=CC=CC=C1

InChI Identifier

InChI=1S/C23H26N2O2.C4H6O4/c26-23(27-21-16-24-13-10-18(21)11-14-24)25-15-12-17-6-4-5-9-20(17)22(25)19-7-2-1-3-8-19;5-3(6)1-2-4(7)8/h1-9,18,21-22H,10-16H2;1-2H2,(H,5,6)(H,7,8)/t21-,22-;/m0./s1

InChI Key

RXZMMZZRUPYENV-VROPFNGYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as 1-phenyltetrahydroisoquinolines. These are compounds containing a phenyl group attached to the C1-atom of a tetrahydroisoquinoline moiety. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Tetrahydroisoquinolines Direct Parent

1-phenyltetrahydroisoquinolines Alternative Parents

  • Quinuclidines
  • Piperidines
  • Dicarboxylic acids and derivatives
  • Benzene and substituted derivatives
  • Carbamate esters
  • Trialkylamines
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organic oxides
  • Hydrocarbon derivatives
  • Carbonyl compounds

    • Substituents

  • 1-phenyltetrahydroisoquinoline
  • Quinuclidine
  • Monocyclic benzene moiety
  • Dicarboxylic acid or derivatives
  • Piperidine
  • Benzenoid
  • Carbamic acid ester
  • Tertiary amine
  • Tertiary aliphatic amine
  • Azacycle
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Amine
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Not Available External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-Incontinence Agents
  • Antispasmodics
  • Muscarinic Antagonists

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water SolubilityNot AvailableNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source logP3.96ChemAxon pKa (Strongest Basic)8.88ChemAxon Physiological Charge1ChemAxon Hydrogen Acceptor Count2ChemAxon Hydrogen Donor Count0ChemAxon Polar Surface Area32.78 Å2ChemAxon Rotatable Bond Count6ChemAxon Refractivity106.06 m3·mol-1ChemAxon Polarizability40.52 Å3ChemAxon Number of Rings5ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Spectrum Type Description Splash Key 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 DB01591

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01591

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01591 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

    187603 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Solifenacin NuGOwiki Link

    HMDB15530 Metagene Link

    HMDB15530 METLIN ID

    Not Available PubChem Compound

    216457 PDB ID

    Not Available ChEBI ID

    774754

    Product: Eribulin

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References Not Available

    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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
    Gene Name:
    CHRM3
    Uniprot ID:
    P20309
    Molecular weight:
    66127.4
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
    3. Ito Y, Oyunzul L, Yoshida A, Fujino T, Noguchi Y, Yuyama H, Ohtake A, Suzuki M, Sasamata M, Matsui M, Yamada S: Comparison of muscarinic receptor selectivity of solifenacin and oxybutynin in the bladder and submandibular gland of muscarinic receptor knockout mice. Eur J Pharmacol. 2009 Aug 1;615(1-3):201-6. doi: 10.1016/j.ejphar.2009.04.068. Epub 2009 May 13. [PubMed:19446545 ]
    4. Sinha S, Gupta S, Malhotra S, Krishna NS, Meru AV, Babu V, Bansal V, Garg M, Kumar N, Chugh A, Ray A: AE9C90CB: a novel, bladder-selective muscarinic receptor antagonist for the treatment of overactive bladder. Br J Pharmacol. 2010 Jul;160(5):1119-27. doi: 10.1111/j.1476-5381.2010.00752.x. [PubMed:20590605 ]
    5. Mansfield KJ, Chandran JJ, Vaux KJ, Millard RJ, Christopoulos A, Mitchelson FJ, Burcher E: Comparison of receptor binding characteristics of commonly used muscarinic antagonists in human bladder detrusor and mucosa. J Pharmacol Exp Ther. 2009 Mar;328(3):893-9. doi: 10.1124/jpet.108.145508. Epub 2008 Nov 24. [PubMed:19029429 ]
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
    Gene Name:
    CHRM1
    Uniprot ID:
    P11229
    Molecular weight:
    51420.4
    References
    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
    3. Sinha S, Gupta S, Malhotra S, Krishna NS, Meru AV, Babu V, Bansal V, Garg M, Kumar N, Chugh A, Ray A: AE9C90CB: a novel, bladder-selective muscarinic receptor antagonist for the treatment of overactive bladder. Br J Pharmacol. 2010 Jul;160(5):1119-27. doi: 10.1111/j.1476-5381.2010.00752.x. [PubMed:20590605 ]
    4. Mansfield KJ, Chandran JJ, Vaux KJ, Millard RJ, Christopoulos A, Mitchelson FJ, Burcher E: Comparison of receptor binding characteristics of commonly used muscarinic antagonists in human bladder detrusor and mucosa. J Pharmacol Exp Ther. 2009 Mar;328(3):893-9. doi: 10.1124/jpet.108.145508. Epub 2008 Nov 24. [PubMed:19029429 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition
    Gene Name:
    CHRM2
    Uniprot ID:
    P08172
    Molecular weight:
    51714.6
    References
    1. Sinha S, Gupta S, Malhotra S, Krishna NS, Meru AV, Babu V, Bansal V, Garg M, Kumar N, Chugh A, Ray A: AE9C90CB: a novel, bladder-selective muscarinic receptor antagonist for the treatment of overactive bladder. Br J Pharmacol. 2010 Jul;160(5):1119-27. doi: 10.1111/j.1476-5381.2010.00752.x. [PubMed:20590605 ]
    2. Mansfield KJ, Chandran JJ, Vaux KJ, Millard RJ, Christopoulos A, Mitchelson FJ, Burcher E: Comparison of receptor binding characteristics of commonly used muscarinic antagonists in human bladder detrusor and mucosa. J Pharmacol Exp Ther. 2009 Mar;328(3):893-9. doi: 10.1124/jpet.108.145508. Epub 2008 Nov 24. [PubMed:19029429 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase
    Gene Name:
    CHRM4
    Uniprot ID:
    P08173
    Molecular weight:
    53048.7
    References
    1. Mansfield KJ, Chandran JJ, Vaux KJ, Millard RJ, Christopoulos A, Mitchelson FJ, Burcher E: Comparison of receptor binding characteristics of commonly used muscarinic antagonists in human bladder detrusor and mucosa. J Pharmacol Exp Ther. 2009 Mar;328(3):893-9. doi: 10.1124/jpet.108.145508. Epub 2008 Nov 24. [PubMed:19029429 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover
    Gene Name:
    CHRM5
    Uniprot ID:
    P08912
    Molecular weight:
    60073.2
    References
    1. Mansfield KJ, Chandran JJ, Vaux KJ, Millard RJ, Christopoulos A, Mitchelson FJ, Burcher E: Comparison of receptor binding characteristics of commonly used muscarinic antagonists in human bladder detrusor and mucosa. J Pharmacol Exp Ther. 2009 Mar;328(3):893-9. doi: 10.1124/jpet.108.145508. Epub 2008 Nov 24. [PubMed:19029429 ]

    PMID: 10741725

    Last updated on