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1-(4-Amino-6,7-dimethoxy-2-chinazolinyl)-4-(2-furoyl)piperazinmonohydrochlorid

Prazosin Hydrochloride

HCID 68546
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Grundinformationen

CAS
19237-84-4
Standard-SMILES
COc1cc2nc(N3CCN(C(=O)c4ccco4)CC3)nc(N)c2cc1OC.Cl
InChIKey
WFXFYZULCQKPIP-UHFFFAOYSA-N
Summenformel
C19H22ClN5O4
Durchschnittliche Molmasse
419,9 g/mol
Monoisotopische Masse
419,13603186

Überblick

Prazosin Hydrochloride is a synthetic piperazine derivative with hypotensive antiadrenergic properties, Prazosin Hydrochloride reduces peripheral resistance and relaxes vascular smooth muscles as a selective adrenergic alpha-1 antagonist by a mechanism not completely known. It is used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. (NCI04)

Namen und Bezeichner

Bevorzugter Name
Prazosin Hydrochloride
IUPAC
[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]-(furan-2-yl)methanone;hydrochloride
Lokaler Name
1-(4-Amino-6,7-dimethoxy-2-chinazolinyl)-4-(2-furoyl)piperazinmonohydrochlorid
Englischer Name
Prazosin hydrochloride
Summenformel
C19H22ClN5O4
Molmasse
419.86

Namen und Synonyme

Prazosin hydrochloride19237-84-4Prazosin HClPeripressMinipress XlHypovaseSinetens1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)piperazine hydrochlorideCP-12299-1Prazosin clorhidratoCP-12,299-11-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furoyl)piperazine monohydrochloride
Weitere Namen anzeigen
(4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl)(furan-2-yl)methanone hydrochloridepratsiolVasoflexAdversuten
X0Z7454B902-(4-(2-Furoyl)piperazin-1-yl)-4-amino-6,7-dimethoxyquinazoline hydrochloridePiperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)-, monohydrochlorideDTXSID50172822NSC2928102-[4-(2-Furoyl)piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline hydrochlorideAlpress LPCHEBI:8365

Datenbank-Bezeichner

CAS
19237-84-4

Eigenschaften

Berechnete Struktureigenschaften

Polarare Oberfläche (TPSA)
107 Ų
H-Brücken-Donoren
2
H-Brücken-Akzeptoren
8
Frei drehbare Bindungen
4
Schwere Atome
29
Formalladung
0
Komplexität
544

Experimentelle und physikochemische Eigenschaften

Color/FormWhite to tan powder
Solubility · 3 Einträge

Soluble at ambient temperatures (mg/ml): acetone, 0.0072; methanol, 6.4; ethanol, 0.84; dimethylformamide, 1.3; dimethylacetamide, 1.2; chloroform, 0.041

In water, 1.4 mg/ml @ pH approx 3.5

61.9 [ug/mL] (The mean of the results at pH 7.4)

Human Drugs · 2 Einträge

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Melting PointCrystals. MP: 278-280 °C /Prazosin/
Stability/Shelf LifePrazosin hydrochloride capsules should be stored in well closed, light resistant containers at 15-30 °C.
Collision Cross Section193.4 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Physikochemische Eigenschaften

Schmelzpunkt
277 · 277 - 280 °C
storage temp.
2 · 2-8°C

Sicherheit und Regulatorisches

Sicherheitsangaben dienen nur zur Orientierung und ersetzen weder das Sicherheitsdatenblatt (SDB) des Lieferanten noch geltende Vorschriften oder eine fachliche Bewertung.

GHS-Klassifizierung

GHS Classification · 4 Einträge

Warning

H302 (56.6%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P260, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 76 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Gefahrenhinweise

Regulatory InformationPrazosin hydrochloride: Does not have an individual approval but may be used under an appropriate group standard
Other Safety InformationIMAP assessments - Piperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)-, monohydrochloride: Environment tier I assessment
FDA Requirements · 2 Einträge

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prazosin hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Special Reports · 1 Eintrag

Khoury AF, Kaplan NM; Alpha-blocker Therapy of Hypertension. An Unfulfilled Promise. JAMA 266 (3): 394-8 (1991). For various reasons, the alpha 1-receptor blocker prazosin has been used infrequently as initial therapy for hypertension. A summary of the published data on efficacy, side effects, and special properties of alpha 1-receptor blockers indicates that they will probably be used more extensively, particularly because of their ability to improve lipid and glucose-insulin metabolism.

Chemie und Industrie

Pharmakologische Informationen

Mechanism of Action · 3 Einträge

Animal studies indicate that prazosin does not have its antihypertensive effect in the CNS. Prazosin does not interfere with nerve impulse transmission across sympathetic ganglia nor does it cause adrenergic neuronal blockade.

The exact mechanism of the hypotensive action of prazosin is unknown. Prazosin causes a decrease in total peripheral resistance and was originally thought to have a direct relaxant action on vascular smooth muscle. Animal studies have suggested that the vasodilator effect of prazosin is also related to blockade of postsynaptic alpha-adrenoceptors. The results of dog forelimb experiments demonstrate that that the peripheral vasodilator effect of prazosin is confined mainly to the level of the resistance vessels (arterioles). Unlike conventional alpha- blockers, the antihypertensive action of prazosin is usually not accompanied by reflex tachycardia.

Prazosin ... is a very potent and selective alpha 1-adrenergic antagonist. ... Interestingly, the drug also is a relatively potent inhibitor of cyclic nucleotide phosphodiesterases...

Biological Half-Life · 2 Einträge

Elimination half-life approx 3 hr.

The plasma half-life of prazosin after oral administration has been reported to be 2-4 hr.

Metabolism/Metabolites · 2 Einträge

Animal studies show that prazosin hydrochloride is metabolized extensively in the liver, principally by demethylation and conjugation, and excreted as unchanged drug (5-11%) and metabolites. Four of the metabolites have been shown to possess 10-25% of the hypotensive activity of prazosin and they may contribute to the antihypertensive effect of the drug.

The 6-O-demethyl and 7-O-demethyl analogues of the new antihypertensive drug prazosin [2-[4-(2-furoyl)-piperazin-1-yl]-4-amino-6,7-dimethoxyquinazoline hydrochloride] have been unequivocally synthesized via separate 10-step reaction sequences starting from isovanillin and vanillin, respectively. The 6-O-demethyl derivative was found to be identical with the major prazosin metabolite formed in dog and rat, while the 7-O-demethyl derivative was identical with another, less prevalent but significant metabolite. Two minor metabolites of prazosin, 2-(1-piperazinyl)-4-amino-6,7-dimethoxyquinazoline and 2,4-diamino-6,7-dimethoxyquinazoline, are also described. All 4 metabolites are less potent blood pressure lowering agents in dogs than prazosin but may contribute to its antihypertensive effect, since they account for a major portion of the administered dose.

Zugehörige Reaktionen

4
Reaktionsaufzeichnung erstellen
Reaktionsgleichung von HRID 372679
HRID 372679als Produktuspto-grants-1978_05
Reaktionsgleichung von HRID 372680
HRID 372680als Eduktuspto-grants-1978_05
Reaktionsgleichung von HRID 840093
HRID 840093als Eduktuspto-grants-2002_04
Reaktionsgleichung von HRID 1680075
HRID 1680075als Produktuspto-grants-1981_06

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Auf dieser SeiteGrundinformationenÜberblickNamen und BezeichnerEigenschaftenSicherheit und RegulatorischesChemie und IndustrieZugehörige ReaktionenNotizen zur Verbindung
PubChem CID
68546
DTXSID
DTXSID50172822
ChEMBL
CHEMBL1558
UNII
X0Z7454B90
EC Number
242-903-4
Löslichkeit
2 O: · H2O: 1 mg/mL, clear, colorless
Aggregatzustand
solid
Farbe
white
Wasserlöslichkeit
Soluble in dimethyl sulfoxide, ethanol, water, methanol.
Merck
14 · 14,7717
BRN
4303561 · 4303561
InChI
InChI=1S/C19H21N5O4.ClH/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;/h3-4,9-11H,5-8H2,1-2H3,(H2,20,21,22);1H
InChIKey
WFXFYZULCQKPIP-UHFFFAOYSA-N
SMILES
N1(C2=NC(N)=C3C(=N2)C=C(OC)C(OC)=C3)CCN(C(C2=CC=CO2)=O)CC1.[H]Cl
CAS Datenbank
19237 · 19237-84-4(CAS DataBase Reference)
Hazard Classes and CategoriesAcute Tox. 4 (56.6%)

Sicherheit und Schutzausrüstung

Disposal Methods · 1 Eintrag

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Toxikologische Informationen

Interactions · 2 Einträge

When prazosin is administered with diuretics or other hypotensive agents, particularly beta-adrenergic blocking agents (eg, propranolol), the hypotensive effect of prazosin may be increased.

... prazosin hydrochloride has been administered without any adverse drug interaction in limited clinical experience to date with the following: cardiac glycosides -- digitalis and digoxin; hypoglycemics -- insulin, chlorpropamide, phenformin, tolazamide, and tolbutamide; tranquilizers and sedatives -- chlordiazepoxide, diazepam, phenobarbital; antigout -- allopurinol, colchicine, and probenecid; antiarrhythmics -- procainamide, propranolol and quinidine; analgesics, antipyretics and anti-inflammatories -- propoxyphene, aspirin, indomethacin, and phenylbutazone.

Milk Concentrations/Prazosin hydrochloride/ has been shown to be excreted in small amounts in human milk.
Human Toxicity Excerpts · 2 Einträge

/HUMAN EXPOSURE STUDIES/ In overdosage, hypotension and CNS depression ranging from lethargy to coma are reported. In addition, priapism may occur.

/CASE REPORTS/ Ingestion of at least 50 mg of prazosin by a 2 yr old child produced profound drowsiness and depressed reflexes. There was no decrease in blood pressure and recovery was uneventful. A 19 yr old man who ingested approximately 200 mg of prazosin had normal CNS responses and slightly decreased blood pressure.

Drug Induced Liver Injury · 6 Einträge

Drug Induced Liver Injury Rank (DILIrank 2.0)

Prazosin hydrochloride

Ambiguous-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

Non-Human Toxicity Excerpts · 5 Einträge

/LABORATORY ANIMALS: Acute Exposure/ ... Prazosin has been shown to exacerbate canine narcolepsy-cataplexy, probably secondary to inhibition of a subtype of alpha1-adrenergic receptor (eg, alpha1b) in the CNS.

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ No carcinogenic potential was demonstrated in an 18 month study in rats with /prazosin hydrochloride/ ... at dose levels more than 225 times the usual maximum recommended human dose of 20 mg per day.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ /prazosin hydrochloride/ ... has been shown to be associated with decreased litter size at birth 1, 4, and 21 days of age in rats when given doses more than 225 times the usual maximum recommended human dose. No evidence of drug-related external, visceral, or skeletal fetal abnormalities were observed. No drug-related external, visceral, or skeletal abnormalities were observed in fetuses of pregnant rabbits and pregnant monkeys at doses more than 225 times and 12 times the usual maximum recommended human dose respectively.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Decreased fertility has occurred in male and female rats receiving prazosin dosages of 75 mg/kg but did not occur in those receiving 25 mg/kg. Testicular changes consisting of atrophy and necrosis have occurred in rats and dogs receiving prazosin dosages of 25 mg/kg daily for a year or longer but no such changes occurred in those receiving 10 mg/kg daily.

For more Non-Human Toxicity Excerpts (Complete) data for PRAZOSIN HYDROCHLORIDE (6 total), please visit the HSDB record page.

Antidote and Emergency Treatment · 2 Einträge

Treatment with supportive care including intravenous fluid boluses and vasopressors such as dopamine were effective in the few overdose cases reported.

Maintain an open airway and assist ventilation if necessary.Hypotension usually respondes to supine positioning and iv crystalloid fluids. Occasionally pressor therapy is needed. there is no specific antidote. Administer activated charcoal.

Regulatorische Informationen

FDA Requirements · 2 Einträge

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl prazosin hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Sicherheitsdaten

F
10
wgk
3
ridadr
3249
hs_code
2934990002
RTECS-Nr.
VA1350000
risk_code
22-36/37/38-62
Toxizität
dog,LD50,oral,> 700mg/kg (700mg/kg),GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDSKIDNEY, URETER, AND BLADDER: OTHER CHANGES GASTROINTESTINAL: NAUSEA OR VOMITING,Oyo Yakuri. Pharmacometrics. Vol. 17, Pg. 39, 1979.
hazard_code
Xn
safety_code
28-36
hazard_class
6.1(b)
packing_group
III
Speicherklasse
11 - Combustible Solids
Giftige Stoffe Daten
19237-84-4(Hazardous Substances Data)
Hazard Classifications
Repr. 2STOT RE 2STOT SE 3
FDA Pharmacological Classification · 4 Einträge

PRAZOSIN HCL

alpha-Adrenergic Blocker [EPC]; Adrenergic alpha-Antagonists [MoA]

PRAZOSIN HYDROCHLORIDE

Adrenergic alpha-Antagonists [MoA]; alpha-Adrenergic Blocker [EPC]

MeSH Pharmacological Classification · 2 Einträge

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.

Absorption, Distribution and Excretion · 5 Einträge

There is intraindividual and interindividual variation in the rate of absorption and plasma concentrations of prazosin. The absolute oral bioavailability of prazosin is also variable but is reported to average about 60% (range: 43-82%). Results of one study indicate that the presence of food may delay absorption of the drug in some patients, but does not affect the extent of absorption.

Following oral administration of prazosin hydrochloride, plasma concentrations of the drug reach a peak in 2-3 hrs in most fasting patients. Plasma concentrations of prazosin generally do not correlate with therapeutic effect. One manufacturer reports that plasma concentrations of the drug after a single 5 mg dose range from 0.01-0.075 ug/ml. Blood pressure begins to decrease within 2 hr after an oral dose; the maximum decrease occurs in 2-4 hr. The hypotensive effect of prazosin lasts less than 24 hr.

Animal studies indicate that prazosin is widely distributed in body tissues. After iv administration in dogs, highest concentrations of the drug are found in the lungs, coronary arteries, aorta, paw arteries and heart; the lowest concentrations are in the brain. During prazosin therapy, approximately 97% of the drug in plasma is bound to proteins. It is not known whether the drug crosses the placenta. Prazosin is distributed into milk in small amounts.

Approximately 6-10% of a dose is excreted in urine and the remainder in feces via bile.

The drug /prazosin hydrochloride/ is tightly bound to plasma proteins (primarily alpha1-acid glycoprotein), and only 5% of the drug is free in the circulation; diseases that modify the concentration of this protein (e.g., inflammatory processes) may change the free fraction. Prazosin is extensively metabolized in the liver, and little unchanged drug is excreted by the kidneys.

Verwendung und Herstellung

Uses · 2 Einträge

MEDICATION

Use (kg; approx.) in Germany (2009): >10

Methods of ManufacturingPreparation: GB 1156973; Hess, US 3511836 (1969, 1970 both to Pfizer); Nl 7206067 (1972 to Brocades-Stheeman) ... . /Prazosin/
Formulations/Preparations · 5 Einträge

Oral Capsules, 1 mg (of prazosin), Minipress, Pifizer; 2 mg (of prazosin), Minipress, Pifzer; 5 mg (of prazosin), Minipress, Pifizer.

Oral Capsules, 1 mg (of prazosin) with Polythiazide 0.5 mg, Minizide 1, Pifizer; 2 mg (of prazosin) with Polythiazide 0.5 mg, Minizide 2, Pfizer; 5 mg (of prazosin) with Polythiazide 0.5 mg, Minizide 5, Pfizer.

Capsules, 1, 2, and 5 mg /Prazosin HCl/

1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furanylcarbonyl)piperazine.

2-(4-(2-FUROYL)PIPERAZIN-1-YL)-4-AMINO-6,7-DIMETHOXYQUINAZOLINE

Anwendungen

VerwendenPrazosin Hydrochloride (Terazosin EP Impurity K) is an antihypertensive. α1-Adrenergic blocker.

Vor- und nachgelagerte Produkte

Vorgelagerte Rohstoffe

2,4-Dichloro-6,7-dihydro-5H-cyclopentapyrimidine2-FuroylchloridAmmoniak, wasserfrei2-Chlor-6,7-dimethoxychinazolin-4-aminPiperazin

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