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Record Information
Version3.6
Creation Date2012-09-06 15:16:52 UTC
Update Date2016-02-11 01:32:44 UTC
HMDB IDHMDB15399
Secondary Accession NumbersNone
Metabolite Identification
Common NameArformoterol
DescriptionArformoterol is a bronchodilator. It works by relaxing muscles in the airways to improve breathing. Arformoterol inhalation is used to prevent bronchoconstriction in people with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema. The use of arformoterol is pending revision due to safety concerns in regards to an increased risk of severe exacerbation of asthma symptoms, leading to hospitalization as well as death in some patients using long acting beta agonists for the treatment of asthma.
Structure
Thumb
Synonyms
ValueSource
(-)-FormoterolChEBI
(R,R)-FormoterolChEBI
Chemical FormulaC19H24N2O4
Average Molecular Weight344.4049
Monoisotopic Molecular Weight344.173607266
IUPAC NameN-{2-hydroxy-5-[(1R)-1-hydroxy-2-{[(2R)-1-(4-methoxyphenyl)propan-2-yl]amino}ethyl]phenyl}formamide
Traditional Namearformoterol
CAS Registry Number67346-49-0
SMILES
COC1=CC=C(C[C@@H](C)NC[C@H](O)C2=CC(NC=O)=C(O)C=C2)C=C1
InChI Identifier
InChI=1S/C19H24N2O4/c1-13(9-14-3-6-16(25-2)7-4-14)20-11-19(24)15-5-8-18(23)17(10-15)21-12-22/h3-8,10,12-13,19-20,23-24H,9,11H2,1-2H3,(H,21,22)/t13-,19+/m1/s1
InChI KeyInChIKey=BPZSYCZIITTYBL-YJYMSZOUSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenethylamines
Direct ParentAmphetamines and derivatives
Alternative Parents
Substituents
  • Amphetamine or derivatives
  • Phenylpropane
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Aralkylamine
  • Phenol
  • Alkyl aryl ether
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • 1,2-aminoalcohol
  • Secondary amine
  • Ether
  • Secondary aliphatic amine
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
  • N-[2-hydroxy-5-(1-hydroxy-2-\{[1-(4-methoxyphenyl)propan-2-yl]amino\}ethyl)phenyl]formamide (CHEBI:408174 )
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Adrenergic beta-Agonists
  • Bronchodilator Agents
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility4.16e-02 g/LNot Available
LogP2.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.042 mg/mLALOGPS
logP1.91ALOGPS
logP1.06ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)8.61ChemAxon
pKa (Strongest Basic)9.81ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area90.82 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity97.87 m3·mol-1ChemAxon
Polarizability36.56 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01274
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01274
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01274
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2340731
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
NuGOwiki LinkHMDB15399
Metagene LinkHMDB15399
METLIN IDNot Available
PubChem Compound3083544
PDB IDNot Available
ChEBI ID408174
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Cazzola M, Matera MG, Lotvall J: Ultra long-acting beta 2-agonists in development for asthma and chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2005 Jul;14(7):775-83. [16022567 ]
  2. Kharidia J, Fogarty CM, Laforce CF, Maier G, Hsu R, Dunnington KM, Curry L, Baumgartner RA, Hanrahan JP: A pharmacokinetic/pharmacodynamic study comparing arformoterol tartrate inhalation solution and racemic formoterol dry powder inhaler in subjects with chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2008 Aug;21(4):657-62. Epub 2008 Apr 7. [18501650 ]
  3. Baumgartner RA, Hanania NA, Calhoun WJ, Sahn SA, Sciarappa K, Hanrahan JP: Nebulized arformoterol in patients with COPD: a 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial. Clin Ther. 2007 Feb;29(2):261-78. [17472819 ]
  4. Donohue JF, Hanania NA, Sciarappa KA, Goodwin E, Grogan DR, Baumgartner RA, Hanrahan JP: Arformoterol and salmeterol in the treatment of chronic obstructive pulmonary disease: a one year evaluation of safety and tolerance. Ther Adv Respir Dis. 2008 Apr;2(2):37-48. doi: 10.1177/1753465808089455. [19124357 ]
  5. Panettieri RA Jr, MacIntyre N, Sims M, Kerwin E, Fogarty C, Noonan M, Claus R, Andrews WT: Comparison of the efficacy and safety of arformoterol 15 microg twice daily and arformoterol 30 microg once daily in COPD: a single-dose, multicenter, randomized, modified-blind, two-way crossover study. Clin Ther. 2009 Aug;31(8):1716-23. doi: 10.1016/j.clinthera.2009.08.012. [19808130 ]
  6. Hanania NA, Donohue JF, Nelson H, Sciarappa K, Goodwin E, Baumgartner RA, Hanrahan JP: The safety and efficacy of arformoterol and formoterol in COPD. COPD. 2010 Feb;7(1):17-31. doi: 10.3109/15412550903499498. [20214460 ]

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 oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
References
  1. Somers GI, Lindsay N, Lowdon BM, Jones AE, Freathy C, Ho S, Woodrooffe AJ, Bayliss MK, Manchee GR: A comparison of the expression and metabolizing activities of phase I and II enzymes in freshly isolated human lung parenchymal cells and cryopreserved human hepatocytes. Drug Metab Dispos. 2007 Oct;35(10):1797-805. Epub 2007 Jul 12. [17627976 ]
  2. Zhang M, Fawcett JP, Kennedy JM, Shaw JP: Stereoselective glucuronidation of formoterol by human liver microsomes. Br J Clin Pharmacol. 2000 Feb;49(2):152-7. [10671910 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
References
  1. Somers GI, Lindsay N, Lowdon BM, Jones AE, Freathy C, Ho S, Woodrooffe AJ, Bayliss MK, Manchee GR: A comparison of the expression and metabolizing activities of phase I and II enzymes in freshly isolated human lung parenchymal cells and cryopreserved human hepatocytes. Drug Metab Dispos. 2007 Oct;35(10):1797-805. Epub 2007 Jul 12. [17627976 ]
  2. Zhang M, Fawcett JP, Kennedy JM, Shaw JP: Stereoselective glucuronidation of formoterol by human liver microsomes. Br J Clin Pharmacol. 2000 Feb;49(2):152-7. [10671910 ]
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Somers GI, Lindsay N, Lowdon BM, Jones AE, Freathy C, Ho S, Woodrooffe AJ, Bayliss MK, Manchee GR: A comparison of the expression and metabolizing activities of phase I and II enzymes in freshly isolated human lung parenchymal cells and cryopreserved human hepatocytes. Drug Metab Dispos. 2007 Oct;35(10):1797-805. Epub 2007 Jul 12. [17627976 ]
  2. Zhang M, Fawcett JP, Kennedy JM, Shaw JP: Stereoselective glucuronidation of formoterol by human liver microsomes. Br J Clin Pharmacol. 2000 Feb;49(2):152-7. [10671910 ]
General function:
Involved in monooxygenase activity
Specific function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Molecular weight:
56517.005
References
  1. Somers GI, Lindsay N, Lowdon BM, Jones AE, Freathy C, Ho S, Woodrooffe AJ, Bayliss MK, Manchee GR: A comparison of the expression and metabolizing activities of phase I and II enzymes in freshly isolated human lung parenchymal cells and cryopreserved human hepatocytes. Drug Metab Dispos. 2007 Oct;35(10):1797-805. Epub 2007 Jul 12. [17627976 ]
  2. Zhang M, Fawcett JP, Kennedy JM, Shaw JP: Stereoselective glucuronidation of formoterol by human liver microsomes. Br J Clin Pharmacol. 2000 Feb;49(2):152-7. [10671910 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. The beta-2-adrenergic receptor binds epinephrine with an approximately 30-fold greater affinity than it does norepinephrine
Gene Name:
ADRB2
Uniprot ID:
P07550
Molecular weight:
46458.3
References
  1. [No authors listed]Arformoterol: (R,R)-eformoterol, (R,R)-formoterol, arformoterol tartrate, eformoterol-sepracor, formoterol-sepracor, R,R-eformoterol, R,R-formoterol. Drugs R D. 2004;5(1):25-7. [14725487 ]
  2. Op't Holt TB: Inhaled beta agonists. Respir Care. 2007 Jul;52(7):820-32. [17594727 ]
  3. Matera MG, Cazzola M: ultra-long-acting beta2-adrenoceptor agonists: an emerging therapeutic option for asthma and COPD? Drugs. 2007;67(4):503-15. [17352511 ]
  4. Cazzola M, Hanania NA, Matera MG: Arformoterol tartrate in the treatment of COPD. Expert Rev Respir Med. 2010 Apr;4(2):155-62. [20406080 ]
  5. Cazzola M, Matera MG, Lotvall J: Ultra long-acting beta 2-agonists in development for asthma and chronic obstructive pulmonary disease. Expert Opin Investig Drugs. 2005 Jul;14(7):775-83. [16022567 ]
  6. Kharidia J, Fogarty CM, Laforce CF, Maier G, Hsu R, Dunnington KM, Curry L, Baumgartner RA, Hanrahan JP: A pharmacokinetic/pharmacodynamic study comparing arformoterol tartrate inhalation solution and racemic formoterol dry powder inhaler in subjects with chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2008 Aug;21(4):657-62. Epub 2008 Apr 7. [18501650 ]
  7. Baumgartner RA, Hanania NA, Calhoun WJ, Sahn SA, Sciarappa K, Hanrahan JP: Nebulized arformoterol in patients with COPD: a 12-week, multicenter, randomized, double-blind, double-dummy, placebo- and active-controlled trial. Clin Ther. 2007 Feb;29(2):261-78. [17472819 ]
  8. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]