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Record Information
Version2.0
Creation Date2009-07-30 17:59:10 UTC
Update Date2014-12-24 20:26:08 UTC
Accession NumberT3D3537
Identification
Common NameTerazosin
ClassSmall Molecule
DescriptionTerazosin is a selective alpha 1 antagonist used for treatment of symptoms of prostate enlargement (BPH). It also acts to lower blood pressure, so it is a drug of choice for men with hypertension and prostate enlargement. It works by blocking the action of adrenaline on smooth muscle of the bladder and the blood vessel walls.
Compound Type
  • Adrenergic alpha-1 Receptor Antagonist
  • Adrenergic alpha-Antagonist
  • Amide
  • Amine
  • Antineoplastic Agent
  • Drug
  • Ether
  • Organic Compound
  • Platelet Aggregation Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-((tetrahydro-2-furanyl)carbonyl)piperazine
Blavin
Flumarc
Fosfomic
Heitrin
Hytrin
Hytrinex
Itrin
Terazosin
Terazosina
Terazosine
Terazosinum
Urodie
Vicard
Zayasel
Chemical FormulaC19H25N5O4
Average Molecular Mass387.433 g/mol
Monoisotopic Mass387.191 g/mol
CAS Registry Number70024-40-7
IUPAC Name6,7-dimethoxy-2-[4-(oxolane-2-carbonyl)piperazin-1-yl]quinazolin-4-amine
Traditional Nameterazosin
SMILESCOC1=C(OC)C=C2C(=N)NC(=NC2=C1)N1CCN(CC1)C(=O)C1CCCO1
InChI IdentifierInChI=1/C19H25N5O4/c1-26-15-10-12-13(11-16(15)27-2)21-19(22-17(12)20)24-7-5-23(6-8-24)18(25)14-4-3-9-28-14/h10-11,14H,3-9H2,1-2H3,(H2,20,21,22)
InChI KeyInChIKey=VCKUSRYTPJJLNI-UHFFFAOYNA-N
Chemical Taxonomy
Description 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
  • Diazanaphthalene
  • Quinazoline
  • Anisole
  • Dialkylarylamine
  • Alkyl aryl ether
  • Aminopyrimidine
  • Pyrimidine
  • Imidolactam
  • Benzenoid
  • Heteroaromatic compound
  • Tetrahydrofuran
  • Tertiary carboxylic acid amide
  • Amino acid or derivatives
  • Carboxamide group
  • Carboxylic acid derivative
  • Dialkyl ether
  • Ether
  • Oxacycle
  • Azacycle
  • Organic oxygen compound
  • Amine
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Organonitrogen compound
  • Organooxygen compound
  • Primary amine
  • Organopnictogen compound
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceTerazosin is a white, crystalline substance,
Experimental Properties
PropertyValue
Melting Point273°C
Boiling PointNot Available
Solubility29.7mg/mL
LogP1
Predicted Properties
PropertyValueSource
Water Solubility1.5 g/LALOGPS
logP1.12ALOGPS
logP1.18ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)19.93ChemAxon
pKa (Strongest Basic)7.24ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area103.04 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity105.18 m³·mol⁻¹ChemAxon
Polarizability41.26 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00di-9375000000-51e0b50a02ca9182132aJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000i-0049000000-86650e3e374df663aa35JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-0049000000-86650e3e374df663aa35JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-0059000000-ca9adf5daab9e5e9b6e7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000e-1292000000-9081c5bb64e8d096db78JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0029000000-b9509509936fd20822e4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-007c-3069000000-196d536a1f876cf3fe0fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-006t-2090000000-f24db01089337864b16fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-1019000000-f4c3728d09b25d55b2f4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00dr-6098000000-81e55b539bff87910453JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00em-3091000000-b40b6a5be295255d01eaJSpectraViewer
Toxicity Profile
Route of ExposureOral. Essentially completely absorbed in man (90% bioavailability).
Mechanism of ToxicityTerazosin selectively and competitively inhibits vascular postsynaptic alpha(1)-adrenergic receptors, resulting in peripheral vasodilation and a reduction of vascular resistance and blood pressure. Unlike the nonselective alph-adrenergic blockers phenoxybenzamine and phentolamine, terazosin does not block presynaptic alpha(2)-receptors and, hence, does not cause reflex activation of norepinephrine release to produce reflex tachycardia.
MetabolismHepatic. One of the four metabolites identified (piperazine derivative of terazosin) has antihypertensive activity. Route of Elimination: Approximately 10% of an orally administered dose is excreted as parent drug in the urine and approximately 20% is excreted in the feces. Half Life: 12 hours
Toxicity ValuesLD50: 259.3mg/kg (parental-intravenous, Mouse) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesTerazosin is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH). There is a rapid response, with approximately 70% of patients experiencing an increase in urinary flow and improvement in symptoms of BPH when treated with terazosin. The long-term effects of terazosin on the incidence of surgery, acute urinary obstruction or other complications of BPH are yet to be determined. Terazosin tablets are also indicated for the treatment of hypertension. Terazosin tablets can be used alone or in combination with other antihypertensive agents such as diuretics or beta-adrenergic blocking agents.
Minimum Risk LevelNot Available
Health EffectsHypotension, palpitations, postural hypotension, syncope, peripheral edema, weight gain, dyspnea, nasal congestion/rhinitis, impotence.
SymptomsAsthenia, postural hypotension, dizziness, somnolence, nasal congestion/rhinitis.
TreatmentShould overdosage of Terazosin lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressors should then be used and renal function should be monitored and supported as needed. Laboratory data indicate that Terazosin is highly protein bound; therefore, dialysis may not be of benefit. (5)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01162
HMDB IDNot Available
PubChem Compound ID5401
ChEMBL IDCHEMBL611
ChemSpider ID5208
KEGG IDC07127
UniProt IDNot Available
OMIM ID
ChEBI ID9445
BioCyc IDNot Available
CTD IDNot Available
Stitch IDTerazosin
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkTerazosin
References
Synthesis Reference

K. S. Keshava Murthy, Gamini Weeratunga, Tianhao Zhou, Bhaskar Reddy Guntoori, “Process for the manufacture of intermediates suitable to make doxazosin, terazosin, prazosin, tiodazosin and related antihypertensive medicines.” U.S. Patent US5919931, issued September, 1986.

MSDST3D3537.pdf
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. 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 ]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
  5. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Protein heterodimerization activity
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. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine(PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1A
Uniprot ID:
P35348
Molecular Weight:
51486.005 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Na YJ, Guo YL, Gu FL: Clinical comparison of selective and non-selective alpha 1A-adrenoceptor antagonists for bladder outlet obstruction associated with benign prostatic hyperplasia: studies on tamsulosin and terazosin in Chinese patients. The Chinese Tamsulosin Study Group. J Med. 1998;29(5-6):289-304. [10503165 ]
  3. Lee E, Lee C: Clinical comparison of selective and non-selective alpha 1A-adrenoreceptor antagonists in benign prostatic hyperplasia: studies on tamsulosin in a fixed dose and terazosin in increasing doses. Br J Urol. 1997 Oct;80(4):606-11. [9352700 ]
  4. 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 ]
  5. 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 ]
  6. Chapple CR: Medical therapy and quality of life. Eur Urol. 1998;34 Suppl 2:10-7; discussion 46. [9732824 ]
General Function:
Protein heterodimerization activity
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. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Gene Name:
ADRA1B
Uniprot ID:
P35368
Molecular Weight:
56835.375 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Boyle P, Robertson C, Manski R, Padley RJ, Roehrborn CG: Meta-analysis of randomized trials of terazosin in the treatment of benign prostatic hyperplasia. Urology. 2001 Nov;58(5):717-22. [11711348 ]
  3. Vincent J, Dachman W, Blaschke TF, Hoffman BB: Pharmacological tolerance to alpha 1-adrenergic receptor antagonism mediated by terazosin in humans. J Clin Invest. 1992 Nov;90(5):1763-8. [1358918 ]
  4. Simpson P: Stimulation of hypertrophy of cultured neonatal rat heart cells through an alpha 1-adrenergic receptor and induction of beating through an alpha 1- and beta 1-adrenergic receptor interaction. Evidence for independent regulation of growth and beating. Circ Res. 1985 Jun;56(6):884-94. [2988814 ]
General Function:
Alpha1-adrenergic receptor activity
Specific Function:
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name:
ADRA1D
Uniprot ID:
P25100
Molecular Weight:
60462.205 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
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). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
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:
Voltage-gated potassium channel activity
Specific Function:
Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current (By similarity). Channel properties may be modulated by cAMP and subunit assembly.
Gene Name:
KCNH6
Uniprot ID:
Q9H252
Molecular Weight:
109923.705 Da
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:
Voltage-gated potassium 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:
134998.525 Da
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 ]