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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2021-09-14 15:47:12 UTC
HMDB IDHMDB0014517
Secondary Accession Numbers
  • HMDB14517
Metabolite Identification
Common NameTimolol
DescriptionTimolol is only found in individuals that have used or taken this drug. It is a beta-adrenergic antagonist similar in action to propranolol. The levo-isomer is the more active. Timolol has been proposed as an antihypertensive, antiarrhythmic, antiangina, and antiglaucoma agent. It is also used in the treatment of migraine disorders and tremor. [PubChem]Like propranolol and nadolol, timolol competes with adrenergic neurotransmitters such as catecholamines for binding at beta(1)-adrenergic receptors in the heart and vascular smooth muscle and beta(2)-receptors in the bronchial and vascular smooth muscle. Beta(1)-receptor blockade results in a decrease in resting and exercise heart rate and cardiac output, a decrease in both systolic and diastolic blood pressure, and, possibly, a reduction in reflex orthostatic hypotension. Beta(2)-blockade results in an increase in peripheral vascular resistance. The exact mechanism whereby timolol reduces ocular pressure is still not known. The most likely action is by decreasing the secretion of aqueous humor.
Structure
Data?1582753188
Synonyms
ValueSource
Timolol maleateHMDB
Chemical FormulaC13H24N4O3S
Average Molecular Weight316.42
Monoisotopic Molecular Weight316.156911344
IUPAC Name1-(tert-butylamino)-3-{[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy}propan-2-ol
Traditional Name1-(tert-butylamino)-3-{[4-(morpholin-4-yl)-1,2,5-thiadiazol-3-yl]oxy}propan-2-ol
CAS Registry Number26839-75-8
SMILES
CC(C)(C)NCC(O)COC1=NSN=C1N1CCOCC1
InChI Identifier
InChI=1S/C13H24N4O3S/c1-13(2,3)14-8-10(18)9-20-12-11(15-21-16-12)17-4-6-19-7-5-17/h10,14,18H,4-9H2,1-3H3
InChI KeyBLJRIMJGRPQVNF-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as dialkylarylamines. These are aliphatic aromatic amines in which the amino group is linked to two aliphatic chains and one aromatic group.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassAmines
Direct ParentDialkylarylamines
Alternative Parents
Substituents
  • Dialkylarylamine
  • Alkyl aryl ether
  • Morpholine
  • Oxazinane
  • Imidolactam
  • Azole
  • Heteroaromatic compound
  • Thiadiazole
  • 1,2-aminoalcohol
  • Secondary alcohol
  • Secondary amine
  • Oxacycle
  • Ether
  • Secondary aliphatic amine
  • Dialkyl ether
  • Azacycle
  • Organoheterocyclic compound
  • Alcohol
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location

Source

Route of exposure

Process

Naturally occurring process

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting Point201.5 - 202.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.27 g/LNot Available
LogP1.2Not Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.27 g/LALOGPS
logP10(1.44) g/LALOGPS
logP10(1.34) g/LChemAxon
logS10(-3.1) g/LALOGPS
pKa (Strongest Acidic)14.08ChemAxon
pKa (Strongest Basic)9.76ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area79.74 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity83.92 m³·mol⁻¹ChemAxon
Polarizability33.99 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+170.86531661259
DarkChem[M-H]-166.44231661259

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
TimololCC(C)(C)NCC(O)COC1=NSN=C1N1CCOCC12687.5Standard polar33892256
TimololCC(C)(C)NCC(O)COC1=NSN=C1N1CCOCC12263.3Standard non polar33892256
TimololCC(C)(C)NCC(O)COC1=NSN=C1N1CCOCC12246.1Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Timolol,1TMS,isomer #1CC(C)(C)NCC(COC1=NSN=C1N1CCOCC1)O[Si](C)(C)C2312.9Semi standard non polar33892256
Timolol,1TMS,isomer #2CC(C)(C)N(CC(O)COC1=NSN=C1N1CCOCC1)[Si](C)(C)C2469.1Semi standard non polar33892256
Timolol,2TMS,isomer #1CC(C)(C)N(CC(COC1=NSN=C1N1CCOCC1)O[Si](C)(C)C)[Si](C)(C)C2506.7Semi standard non polar33892256
Timolol,2TMS,isomer #1CC(C)(C)N(CC(COC1=NSN=C1N1CCOCC1)O[Si](C)(C)C)[Si](C)(C)C2595.5Standard non polar33892256
Timolol,2TMS,isomer #1CC(C)(C)N(CC(COC1=NSN=C1N1CCOCC1)O[Si](C)(C)C)[Si](C)(C)C3514.1Standard polar33892256
Timolol,1TBDMS,isomer #1CC(C)(C)NCC(COC1=NSN=C1N1CCOCC1)O[Si](C)(C)C(C)(C)C2476.2Semi standard non polar33892256
Timolol,1TBDMS,isomer #2CC(C)(C)N(CC(O)COC1=NSN=C1N1CCOCC1)[Si](C)(C)C(C)(C)C2692.5Semi standard non polar33892256
Timolol,2TBDMS,isomer #1CC(C)(C)N(CC(COC1=NSN=C1N1CCOCC1)O[Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C2924.8Semi standard non polar33892256
Timolol,2TBDMS,isomer #1CC(C)(C)N(CC(COC1=NSN=C1N1CCOCC1)O[Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C2978.4Standard non polar33892256
Timolol,2TBDMS,isomer #1CC(C)(C)N(CC(COC1=NSN=C1N1CCOCC1)O[Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C3550.2Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Timolol GC-MS (Non-derivatized) - 70eV, Positivesplash10-053i-9450000000-c872ba8810b30fc4ea322017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Timolol GC-MS (1 TMS) - 70eV, Positivesplash10-00di-9522000000-5dbd824d871bd6ddbd972017-10-06Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Timolol GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Timolol GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol LC-ESI-QFT , positive-QTOFsplash10-014i-0009000000-26e849bd6770b706d97e2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol LC-ESI-QFT , positive-QTOFsplash10-03di-3192000000-5b0483b3dd1622fa8adf2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol LC-ESI-QFT , positive-QTOFsplash10-00di-9340000000-6db94e778d15328138f42017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol LC-ESI-QFT , positive-QTOFsplash10-05fr-9510000000-25403ac6343ad0f1250e2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol LC-ESI-QFT , positive-QTOFsplash10-05fr-9500000000-28b8084565254a4d462f2017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol LC-ESI-QFT , positive-QTOFsplash10-05fr-9300000000-8b6db6180dcb209d63262017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol LC-ESI-QFT , positive-QTOFsplash10-0ab9-9100000000-bd900d8cca0824ecca362017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol LC-ESI-QFT , positive-QTOFsplash10-0a4i-9000000000-abcab2ee400254c695442017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol LC-ESI-QFT , positive-QTOFsplash10-0a4i-9000000000-e1cdd22ed32eacd8d1862017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol 90V, Positive-QTOFsplash10-05fr-9300000000-812d0b758d8f7d4cf66d2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol 75V, Positive-QTOFsplash10-05fr-9400000000-be31c1dbfaa9fecc653d2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol 60V, Positive-QTOFsplash10-05fr-9510000000-781058aa0fdfde6f17032021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol 45V, Positive-QTOFsplash10-00di-9340000000-597ca11972e488c6dcfb2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol 15V, Positive-QTOFsplash10-014i-0009000000-ef146305d4fbb7ca6b0f2021-09-20HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Timolol 30V, Positive-QTOFsplash10-03di-3092000000-644196ed8441ace2a18d2021-09-20HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Timolol 10V, Positive-QTOFsplash10-014i-2349000000-3a7bd11ebc56e9503dbb2017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Timolol 20V, Positive-QTOFsplash10-03dr-9341000000-0424aeb611cf5b719ac62017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Timolol 40V, Positive-QTOFsplash10-059i-9200000000-3a384c17dae6401c26322017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Timolol 10V, Negative-QTOFsplash10-014i-1819000000-39d2a69dc0dc6df196bb2017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Timolol 20V, Negative-QTOFsplash10-01ti-3931000000-34ebe028409ca50c678e2017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Timolol 40V, Negative-QTOFsplash10-0a4r-4900000000-bb28689e1727816ecdcf2017-09-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Timolol 10V, Positive-QTOFsplash10-014i-0009000000-684173c09d11e32b8b212021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Timolol 20V, Positive-QTOFsplash10-02t9-6397000000-b5f10e24c95b97b7248c2021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Timolol 40V, Positive-QTOFsplash10-0ab9-9510000000-834ebbea262ed01ed0e82021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Timolol 10V, Negative-QTOFsplash10-014i-0009000000-422d7cde58dffea8ee482021-09-24Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00373 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00373 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID5278
KEGG Compound IDC07141
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTimolol
METLIN IDNot Available
PubChem Compound5478
PDB IDNot Available
ChEBI ID39465
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. InChem Data Sheet [Link]

Enzymes

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. 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 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. 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:
Beta-adrenergic receptors mediate the catecholamine- induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular weight:
51322.1
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Nieminen T, Uusitalo H, Maenpaa J, Turjanmaa V, Rane A, Lundgren S, Ropo A, Rontu R, Lehtimaki T, Kahonen M: Polymorphisms of genes CYP2D6, ADRB1 and GNAS1 in pharmacokinetics and systemic effects of ophthalmic timolol. A pilot study. Eur J Clin Pharmacol. 2005 Dec;61(11):811-9. Epub 2005 Nov 17. [PubMed:16315032 ]
  3. Varma DR, Shen H, Deng XF, Peri KG, Chemtob S, Mulay S: Inverse agonist activities of beta-adrenoceptor antagonists in rat myocardium. Br J Pharmacol. 1999 Jun;127(4):895-902. [PubMed:10433496 ]
  4. Hirooka K, Kelly ME, Baldridge WH, Barnes S: Suppressive actions of betaxolol on ionic currents in retinal ganglion cells may explain its neuroprotective effects. Exp Eye Res. 2000 May;70(5):611-21. [PubMed:10870519 ]
  5. Bhattacharyya BJ, Lee E, Krupin D, Hockberger P, Krupin T: (-)-Isoproterenol modulation of maxi-K(+) channel in nonpigmented ciliary epithelial cells through a G-protein gated pathway. Curr Eye Res. 2002 Mar;24(3):173-81. [PubMed:12221524 ]
  6. Wang T, Kaumann AJ, Brown MJ: (--)-Timolol is a more potent antagonist of the positive inotropic effects of (--)-adrenaline than of those of (--)-noradrenaline in human atrium. Br J Clin Pharmacol. 1996 Aug;42(2):217-23. [PubMed:8864321 ]
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Fuchsjager-Mayrl G, Markovic O, Losert D, Lucas T, Wachek V, Muller M, Schmetterer L: Polymorphism of the beta-2 adrenoceptor and IOP lowering potency of topical timolol in healthy subjects. Mol Vis. 2005 Sep 23;11:811-5. [PubMed:16205624 ]
  3. Rotmensch HH, Vlasses PH, Feinberg JA, Abrams WB, Ferguson RK: Comparisons of beta-adrenergic blocking properties of S- and R-timolol in humans. J Clin Pharmacol. 1993 Jun;33(6):544-8. [PubMed:8103526 ]
  4. Borger P, Hoekstra Y, Esselink MT, Postma DS, Zaagsma J, Vellenga E, Kauffman HF: Beta-adrenoceptor-mediated inhibition of IFN-gamma, IL-3, and GM-CSF mRNA accumulation in activated human T lymphocytes is solely mediated by the beta2-adrenoceptor subtype. Am J Respir Cell Mol Biol. 1998 Sep;19(3):400-7. [PubMed:9730867 ]
  5. Van der Graaf PH, Saxena PR, Shankley NP, Black JW: Exposure and characterization of the action of noradrenaline at dopamine receptors mediating endothelium-independent relaxation of rat isolated small mesenteric arteries. Br J Pharmacol. 1995 Dec;116(8):3237-42. [PubMed:8719802 ]
  6. Ferro A, Hall JA, Dickerson JE, Brown MJ: A prospective study of the effects of prolonged timolol therapy on alpha- and beta-adrenoceptor and angiotensin II receptor mediated responses in normal subjects. Br J Clin Pharmacol. 1997 Mar;43(3):301-8. [PubMed:9088585 ]
  7. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235 ]

Transporters

General function:
Involved in ATP binding
Specific function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular weight:
141477.3
References
  1. Terao T, Hisanaga E, Sai Y, Tamai I, Tsuji A: Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier. J Pharm Pharmacol. 1996 Oct;48(10):1083-9. [PubMed:8953513 ]