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Brinzolamide

July 24, 2017
Common Name

Brinzolamide Description

Brinzolamide is a highly specific, non-competitive, reversible carbonic anhydrase inhibitor. Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II (CA-II). Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The reslit is a reduction in intraocliar pressure. Brinzolamide is indicated in the treatment of elevated intraocliar pressure in patients with ocliar hypertension or open-angle glaucoma. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source AzoptChEBI Alcon brand OF brinzolamideMeSH Allphar brand OF brinzolamideMeSH

Chemical Formlia

C12H21N3O5S3 Average Molecliar Weight

383.507 Monoisotopic Molecliar Weight

383.064332867 IUPAC Name

(4R)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-2H,3H,4H-1λ⁶-thieno[3,2-e][1,2]thiazine-6-slifonamide Traditional Name

brinzolamide CAS Registry Number

138890-62-7 SMILES

CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S2)S(N)(=O)=O

InChI Identifier

InChI=1S/C12H21N3O5S3/c1-3-14-10-8-15(5-4-6-20-2)23(18,19)12-9(10)7-11(21-12)22(13,16)17/h7,10,14H,3-6,8H2,1-2H3,(H2,13,16,17)/t10-/m0/s1

InChI Key

HCRKCZRJWPKOAR-JTQLQIEISA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as thienothiazines. These are heterocyclic compounds containing a thiophene ring fused to a thiazine. Thiophene is 5-membered ring consisting of four carbon atoms and one slifur atom. Thiazine is a 6-membered ring consisting of four carbon, one nitrogen and one slifur atoms. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Thienothiazines Direct Parent

Thienothiazines Alternative Parents

  • 2,3,5-trisubstituted thiophenes
  • Aralkylamines
  • Organoslifonamides
  • 1,2-thiazines
  • Heteroaromatic compounds
  • Aminoslifonyl compounds
  • Dialkylamines
  • Dialkyl ethers
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Thienothiazine
  • 2,3,5-trisubstituted thiophene
  • Aralkylamine
  • Ortho-thiazine
  • Organoslifonic acid amide
  • Organic slifonic acid or derivatives
  • Organoslifonic acid or derivatives
  • Slifonyl
  • Heteroaromatic compound
  • Aminoslifonyl compound
  • Thiophene
  • Dialkyl ether
  • Secondary aliphatic amine
  • Ether
  • Secondary amine
  • Azacycle
  • Organic nitrogen compound
  • Organoslifur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Amine
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

  • slifonamide (CHEBI:41212 )
  • thienothiazine (CHEBI:41212 )

    • Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Antiglaucomic Agents
  • Carbonic Anhydrase Inhibitors
  • Ophthalmics

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting Point131 °CNot Available Boiling PointNot AvailableNot Available Water Solubility7.13e-01 g/LNot Available LogP-1.8Not Available

    Predicted Properties

    Property Value Source Water Solubility0.71 mg/mLALOGPS logP-0.65ALOGPS logP-0.67ChemAxon logS-2.7ALOGPS pKa (Strongest Acidic)8.19ChemAxon pKa (Strongest Basic)6.78ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count6ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area118.8 Å2ChemAxon Rotatable Bond Count7ChemAxon Refractivity87.2 m3·mol-1ChemAxon Polarizability37.93 Å3ChemAxon Number of Rings2ChemAxon 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 – , positivesplash10-000i-3940000000-29878662225bb11586edView 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

  • Cytoplasm
  • 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 DB01194

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01194

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01194 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

    62077 KEGG Compound ID

    C07760 BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Brinzolamide NuGOwiki Link

    HMDB15325 Metagene Link

    HMDB15325 METLIN ID

    Not Available PubChem Compound

    68844 PDB ID

    BZ1 ChEBI ID

    3176

    Product: 7-Maleimidohexanoic acid N-hydroxysuccinimide ester

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    1. DeSantis L: Preclinical overview of brinzolamide. Surv Ophthalmol. 2000 Jan;44 Suppl 2:S119-29. [PubMed:10665514 ]
    2. Iester M: Brinzolamide ophthalmic suspension: a review of its pharmacology and use in the treatment of open angle glaucoma and ocular hypertension. Clin Ophthalmol. 2008 Sep;2(3):517-23. [PubMed:19668749 ]
    3. Kaup M, Plange N, Niegel M, Remky A, Arend O: Effects of brinzolamide on ocular haemodynamics in healthy volunteers. Br J Ophthalmol. 2004 Feb;88(2):257-62. [PubMed:14736787 ]
    4. Ermis SS, Ozturk F, Inan UU: Comparing the effects of travoprost and brinzolamide on intraocular pressure after phacoemulsification. Eye (Lond). 2005 Mar;19(3):303-7. [PubMed:15258611 ]
    5. Iester M, Altieri M, Michelson G, Vittone P, Traverso CE, Calabria G: Retinal peripapillary blood flow before and after topical brinzolamide. Ophthalmologica. 2004 Nov-Dec;218(6):390-6. [PubMed:15564757 ]

    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 carbonate dehydratase activity
    Specific function:
    Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
    Gene Name:
    CA1
    Uniprot ID:
    P00915
    Molecular weight:
    28870.0
    References
    1. Winum JY, Casini A, Mincione F, Starnotti M, Montero JL, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits. Bioorg Med Chem Lett. 2004 Jan 5;14(1):225-9. [PubMed:14684332 ]
    2. Herkel U, Pfeiffer N: Update on topical carbonic anhydrase inhibitors. Curr Opin Ophthalmol. 2001 Apr;12(2):88-93. [PubMed:11224713 ]
    General function:
    Involved in carbonate dehydratase activity
    Specific function:
    Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.
    Gene Name:
    CA2
    Uniprot ID:
    P00918
    Molecular weight:
    29245.895
    References
    1. Stams T, Chen Y, Boriack-Sjodin PA, Hurt JD, Liao J, May JA, Dean T, Laipis P, Silverman DN, Christianson DW: Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination. Protein Sci. 1998 Mar;7(3):556-63. [PubMed:9541386 ]
    2. DeSantis L: Preclinical overview of brinzolamide. Surv Ophthalmol. 2000 Jan;44 Suppl 2:S119-29. [PubMed:10665514 ]
    3. Winum JY, Casini A, Mincione F, Starnotti M, Montero JL, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits. Bioorg Med Chem Lett. 2004 Jan 5;14(1):225-9. [PubMed:14684332 ]
    4. Boriack-Sjodin PA, Zeitlin S, Chen HH, Crenshaw L, Gross S, Dantanarayana A, Delgado P, May JA, Dean T, Christianson DW: Structural analysis of inhibitor binding to human carbonic anhydrase II. Protein Sci. 1998 Dec;7(12):2483-9. [PubMed:9865942 ]
    5. Ilies M, Supuran CT, Scozzafava A, Casini A, Mincione F, Menabuoni L, Caproiu MT, Maganu M, Banciu MD: Carbonic anhydrase inhibitors: sulfonamides incorporating furan-, thiophene- and pyrrole-carboxamido groups possess strong topical intraocular pressure lowering properties as aqueous suspensions. Bioorg Med Chem. 2000 Aug;8(8):2145-55. [PubMed:11003159 ]
    6. Iester M: Brinzolamide ophthalmic suspension: a review of its pharmacology and use in the treatment of open angle glaucoma and ocular hypertension. Clin Ophthalmol. 2008 Sep;2(3):517-23. [PubMed:19668749 ]
    7. Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. J Med Chem. 2004 Feb 26;47(5):1272-9. [PubMed:14971907 ]
    General function:
    Involved in carbonate dehydratase activity
    Specific function:
    Reversible hydration of carbon dioxide. Low activity.
    Gene Name:
    CA5A
    Uniprot ID:
    P35218
    Molecular weight:
    34750.21
    References
    1. Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. J Med Chem. 2004 Feb 26;47(5):1272-9. [PubMed:14971907 ]
    General function:
    Involved in carbonate dehydratase activity
    Specific function:
    Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
    Gene Name:
    CA4
    Uniprot ID:
    P22748
    Molecular weight:
    35032.075
    References
    1. Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. J Med Chem. 2004 Feb 26;47(5):1272-9. [PubMed:14971907 ]

    PMID: 10764961

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