Bepotastine (T3D3066)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2009-07-21 20:28:59 UTC
Update Date2014-12-24 20:25:56 UTC
Accession NumberT3D3066
Identification
Common NameBepotastine
ClassSmall Molecule
DescriptionBepotastine is a non-sedating, selective antagonist of the histamine 1 (H1) receptor. Bepotastine was approved in Japan for use in the treatment of allergic rhinitis and uriticaria/puritus in July 2000 and January 2002, respectively, and is marketed by Tanabe Seiyaku Co., Ltd. under the brand name Talion. It is available in oral and opthalmic dosage forms in Japan. The opthalmic solution is FDA approved since Sept 8, 2009 and is under the brand name Bepreve.
Compound Type
  • Amine
  • Anti-Allergic Agent
  • Drug
  • Ether
  • Histamine H1 Antagonist, Non-Sedating
  • Mast Cell Stabilizer
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
Bepreve
Talion
TAU-284DS
Chemical FormulaC21H25ClN2O3
Average Molecular Mass388.888 g/mol
Monoisotopic Mass388.155 g/mol
CAS Registry Number125602-71-3
IUPAC Name4-{4-[(4-chlorophenyl)(pyridin-2-yl)methoxy]piperidin-1-yl}butanoic acid
Traditional Nametalion
SMILESOC(=O)CCCN1CCC(CC1)OC(C1=CC=C(Cl)C=C1)C1=CC=CC=N1
InChI IdentifierInChI=1/C21H25ClN2O3/c22-17-8-6-16(7-9-17)21(19-4-1-2-12-23-19)27-18-10-14-24(15-11-18)13-3-5-20(25)26/h1-2,4,6-9,12,18,21H,3,5,10-11,13-15H2,(H,25,26)
InChI KeyInChIKey=YWGDOWXRIALTES-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzylethers
Direct ParentBenzylethers
Alternative Parents
Substituents
  • Benzylether
  • Amino fatty acid
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • Fatty acyl
  • Pyridine
  • Piperidine
  • Heteroaromatic compound
  • Amino acid or derivatives
  • Amino acid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Carboxylic acid derivative
  • Carboxylic acid
  • Azacycle
  • Dialkyl ether
  • Ether
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Organic oxygen compound
  • Organic nitrogen compound
  • Amine
  • Carbonyl group
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organohalogen compound
  • Organochloride
  • Organonitrogen compound
  • Organooxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility5.03e-02 g/L
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.05 g/LALOGPS
logP3.64ALOGPS
logP0.55ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)4.1ChemAxon
pKa (Strongest Basic)9.39ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area62.66 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity105.1 m³·mol⁻¹ChemAxon
Polarizability42.18 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udi-2292000000-5b45fd7805bbbd416e7f2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0udi-2192000000-0ea685d018da4a2938de2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0079-0109000000-324c9088d0c2cb4aac382016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00du-1319000000-6f5aa9888fbcca679b0d2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00du-9820000000-c0621adfa83f3477b8ab2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0019000000-90b8af4e7923949436c22016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00kr-0129000000-4cc6ef36f76266a066982016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-3690000000-f62361da241614f257f02016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-dfc0e49e18673a296c132021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0uki-0049000000-192d682169678552ae492021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uk9-4940000000-4571714c90c45dfd6f352021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0009000000-2f4b05915f2ae5688d7f2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00ku-2119000000-3967902f22f168d220512021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014i-5490000000-80c10183c44faf9ff0272021-10-11View Spectrum
Toxicity Profile
Route of ExposureOral, Ophthalmic. Tmax, after single dose, opthalmic = 1.2 hours; Cmax, 1.5%, opthalmic dose = 7.3 ± 1.9 ng/mL; After 24 hours post-installation, levels of bepotastine are below quantifiable limit of 2 ng/mL. Minimal systemic absorption with opthalmic dosage form.
Mechanism of ToxicityBecause of a type 1 hypersensitivity reaction cascade that is triggered by antigen exposure, allergic conjunctivitis occurs. Allergen exposure is followed by conjunctival mast cell degranulation and histamine released as a result of the formation of complementary IgE cross-links on the conjunctiva. Due to the release of histamine, symptoms such as itching can be observed. Bepotastine works to relieve itchy eyes by three primary mechanisms of action. It is a non-sedating, selective antagonist of the histamine 1 (H1) receptor, a mast cell stabilizer, and it suppresses the migration of eosinophils into inflamed tissues to prevent tissue damage and worsening of allergic inflammation of the conjunctiva.
MetabolismMinimal metabolism via CYP enzymes Route of Elimination: When a oral dose of 2.5 - 40 mg bepotastine is given, 75%-90% of the dose was excreted unchanged in the urine by 24 hours. Half Life: Elimination half life = 2.5 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the symptomatic treatment of itchy eyes (caused by IgE-induced mast cell degranulation) due to allergic conjunctivitis. Used in the treatment of allergic rhinitis and uriticaria/puritus. [Wikipedia]
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB04890
HMDB IDHMDB15600
PubChem Compound ID2350
ChEMBL IDCHEMBL1201758
ChemSpider ID2260
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID71204
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBepotastine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkBepotastine
References
Synthesis Reference

Tae Hee Ha, Chang Hee Park, Won Jeoung Kim, Soohwa Cho, Han Kyong Kim, Kwee Hyun Suh, “PROCESS FOR PREPARING BEPOTASTINE AND INTERMEDIATES USED THEREIN.” U.S. Patent US20100168433, issued July 01, 2010.

MSDST3D3066.pdf
General References
  1. Ohashi R, Kamikozawa Y, Sugiura M, Fukuda H, Yabuuchi H, Tamai I: Effect of P-glycoprotein on intestinal absorption and brain penetration of antiallergic agent bepotastine besilate. Drug Metab Dispos. 2006 May;34(5):793-9. Epub 2006 Feb 2. [16455807 ]
  2. Andoh T, Kuraishi Y: Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice. Eur J Pharmacol. 2006 Oct 10;547(1-3):59-64. Epub 2006 Jul 25. [16914135 ]
  3. Simons FE, Simons KJ: Histamine and H1-antihistamines: celebrating a century of progress. J Allergy Clin Immunol. 2011 Dec;128(6):1139-1150.e4. doi: 10.1016/j.jaci.2011.09.005. Epub 2011 Oct 27. [22035879 ]
  4. Wingard JB, Mah FS: Critical appraisal of bepotastine in the treatment of ocular itching associated with allergic conjunctivitis. Clin Ophthalmol. 2011;5:201-7. doi: 10.2147/OPTH.S8665. Epub 2011 Feb 15. [21386912 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Histamine H1 receptor
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
References
  1. Andoh T, Kuraishi Y: Suppression by bepotastine besilate of substance P-induced itch-associated responses through the inhibition of the leukotriene B4 action in mice. Eur J Pharmacol. 2006 Oct 10;547(1-3):59-64. Epub 2006 Jul 25. [16914135 ]