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Record Information
Version3.6
Creation Date2012-09-06 15:16:50 UTC
Update Date2016-02-11 01:29:43 UTC
HMDB IDHMDB14728
Secondary Accession NumbersNone
Metabolite Identification
Common NameDoxazosin
DescriptionDoxazosin is a quinazoline-derivative that selectively antagonizes postsynaptic α1-adrenergic receptors. It may be used to mild to moderate hypertension and in the management of symptomatic benign prostatic hyperplasia (BPH). α1-Receptors mediate contraction and hypertrophic growth of smooth muscle cells. Antagonism of these receptors leads to smooth muscle relaxation in the peripheral vasculature and prostate gland.
Structure
Thumb
Synonyms
ValueSource
1-(4-amino-6,7-Dimethoxy-2-chinazolinyl)-4-(2,3-dihydro-1,4-benzodioxixin-2-ylcarbonyl)piperazinChEBI
1-(4-amino-6,7-Dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl)piperazinChEBI
DoxazosinaChEBI
DoxazosineChEBI
DoxazosinumChEBI
Doxazosin mesilateHMDB
Chemical FormulaC23H25N5O5
Average Molecular Weight451.4751
Monoisotopic Molecular Weight451.185568935
IUPAC Name2-[4-(2,3-dihydro-1,4-benzodioxine-2-carbonyl)piperazin-1-yl]-6,7-dimethoxyquinazolin-4-amine
Traditional Namedoxazosin
CAS Registry Number74191-85-8
SMILES
COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N1CCN(CC1)C(=O)C1COC2=CC=CC=C2O1
InChI Identifier
InChI=1S/C23H25N5O5/c1-30-18-11-14-15(12-19(18)31-2)25-23(26-21(14)24)28-9-7-27(8-10-28)22(29)20-13-32-16-5-3-4-6-17(16)33-20/h3-6,11-12,20H,7-10,13H2,1-2H3,(H2,24,25,26)
InChI KeyInChIKey=RUZYUOTYCVRMRZ-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-arylpiperazines. These are organic compounds containing a piperazine ring where the nitrogen ring atom carries an aryl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazinanes
Sub ClassPiperazines
Direct ParentN-arylpiperazines
Alternative Parents
Substituents
  • N-arylpiperazine
  • Quinazolinamine
  • Quinazoline
  • Benzodioxane
  • Benzo-p-dioxin
  • Benzo-1,4-dioxane
  • Dialkylarylamine
  • Anisole
  • Aminopyrimidine
  • Alkyl aryl ether
  • Imidolactam
  • Benzenoid
  • Pyrimidine
  • Primary aromatic amine
  • Para-dioxin
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Tertiary amine
  • Carboxamide group
  • Oxacycle
  • Azacycle
  • Ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Adrenergic alpha-Antagonists
  • Alpha-adrenergic Blocking Agents
  • Antihyperplasia Agents
  • Antihypertensive Agents
  • Antineoplastic Agents
  • Vasodilator Agents
Application
  • Pharmaceutical
Cellular locations
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point289 - 290 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility7.90e-01 g/LNot Available
LogP2.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.79 mg/mLALOGPS
logP2.53ALOGPS
logP2.14ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)12.67ChemAxon
pKa (Strongest Basic)7.24ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area112.27 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity121.64 m3·mol-1ChemAxon
Polarizability46.63 Å3ChemAxon
Number of Rings5ChemAxon
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
  • Extracellular
  • 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 DB00590
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00590
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00590
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3045
KEGG Compound IDC06970
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkDoxazosin
NuGOwiki LinkHMDB14728
Metagene LinkHMDB14728
METLIN IDNot Available
PubChem Compound3157
PDB IDNot Available
ChEBI ID4708
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Cushman WC, Ford CE, Cutler JA, Margolis KL, Davis BR, Grimm RH, Black HR, Hamilton BP, Holland J, Nwachuku C, Papademetriou V, Probstfield J, Wright JT Jr, Alderman MH, Weiss RJ, Piller L, Bettencourt J, Walsh SM: Success and predictors of blood pressure control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002 Nov-Dec;4(6):393-404. [12461301 ]

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. Epub 2009 Nov 24. [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. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in ion channel activity
Specific function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular weight:
126653.5
References
  1. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuryshev YA, Kiehn J, Katus HA, Schoels W, Karle CA: Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):462-72. Epub 2004 Apr 20. [15098086 ]
General function:
Involved in ion channel activity
Specific function:
Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current. Channel properties may be modulated by cAMP and subunit assembly
Gene Name:
KCNH6
Uniprot ID:
Q9H252
Molecular weight:
109923.7
References
  1. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuryshev YA, Kiehn J, Katus HA, Schoels W, Karle CA: Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):462-72. Epub 2004 Apr 20. [15098086 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular weight:
51486.0
References
  1. Yono M, Foster HE Jr, Shin D, Takahashi W, Pouresmail M, Latifpour J: Doxazosin-induced up-regulation of alpha 1A-adrenoceptor mRNA in the rat lower urinary tract. Can J Physiol Pharmacol. 2004 Oct;82(10):872-8. [15573147 ]
  2. Michel MC, Grubbel B, Taguchi K, Verfurth F, Otto T, Kropfl D: Drugs for treatment of benign prostatic hyperplasia: affinity comparison at cloned alpha 1-adrenoceptor subtypes and in human prostate. J Auton Pharmacol. 1996 Feb;16(1):21-8. [8736427 ]
  3. Roehrborn CG, Schwinn DA: Alpha1-adrenergic receptors and their inhibitors in lower urinary tract symptoms and benign prostatic hyperplasia. J Urol. 2004 Mar;171(3):1029-35. [14767264 ]
  4. Ishizuka O, Pandita RK, Mattiasson A, Steers WD, Andersson KE: Stimulation of bladder activity by volume, L-dopa and capsaicin in normal conscious rats--effects of spinal alpha 1-adrenoceptor blockade. Naunyn Schmiedebergs Arch Pharmacol. 1997 Jun;355(6):787-93. [9205965 ]
  5. Bae JH, Jung PB, Lee JG: The effects of alpha-adrenoceptor antagonists on the urethral perfusion pressure of the female rat. BJU Int. 2005 Nov;96(7):1131-5. [16225542 ]
  6. Greco KA, McVary KT: The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43. [19002123 ]
  7. Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [17070143 ]
  8. Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [10393471 ]
  9. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular weight:
56835.4
References
  1. Lepor H: Alpha blockers for the treatment of benign prostatic hyperplasia. Rev Urol. 2007 Fall;9(4):181-90. [18231614 ]
  2. Greco KA, McVary KT: The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43. [19002123 ]
  3. Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [17070143 ]
  4. Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [10393471 ]
General function:
Involved in G-protein coupled receptor protein signaling pathway
Specific function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium
Gene Name:
ADRA1D
Uniprot ID:
P25100
Molecular weight:
60462.2
References
  1. Lepor H: Alpha blockers for the treatment of benign prostatic hyperplasia. Rev Urol. 2007 Fall;9(4):181-90. [18231614 ]
  2. Greco KA, McVary KT: The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43. [19002123 ]
  3. Shannon R, Chaudhry M: Effect of alpha1-adrenergic receptors in cardiac pathophysiology. Am Heart J. 2006 Nov;152(5):842-50. [17070143 ]
  4. Martin DJ: Preclinical pharmacology of alpha1-adrenoceptor antagonists. Eur Urol. 1999;36 Suppl 1:35-41; discussion 65. [10393471 ]
General function:
Involved in ion channel activity
Specific function:
Pore-forming (alpha) subunit of voltage-gated potassium channel. Channel properties may be modulated by cAMP and subunit assembly
Gene Name:
KCNH7
Uniprot ID:
Q9NS40
Molecular weight:
134998.5
References
  1. Thomas D, Wimmer AB, Wu K, Hammerling BC, Ficker EK, Kuryshev YA, Kiehn J, Katus HA, Schoels W, Karle CA: Inhibition of human ether-a-go-go-related gene potassium channels by alpha 1-adrenoceptor antagonists prazosin, doxazosin, and terazosin. Naunyn Schmiedebergs Arch Pharmacol. 2004 May;369(5):462-72. Epub 2004 Apr 20. [15098086 ]

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. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K: Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500. [11895100 ]
  2. Takara K, Sakaeda T, Kakumoto M, Tanigawara Y, Kobayashi H, Okumura K, Ohnishi N, Yokoyama T: Effects of alpha-adrenoceptor antagonist doxazosin on MDR1-mediated multidrug resistance and transcellular transport. Oncol Res. 2009;17(11-12):527-33. [19806783 ]