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Alfuzosin, 塩酸アルフゾシン

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Image result for alfuzosinChemSpider 2D Image | Alfuzosin | C19H27N5O4

Alfuzosin

  • Molecular FormulaC19H27N5O4
  • Average mass389.449 Da
N-{3-[(4-Amino-6,7-dimethoxy-2-quinazolinyl)(methyl)amino]propyl}tetrahydro-2-furancarboxamide
N-{3-[(4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl}tetrahydrofuran-2-carboxamide
SL 77499-10
UNII:90347YTW5F
Urion
Xatral
2-furancarboxamide, N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-
5357
cas 81403-80-7 [RN]
CAS: 81403-68-1  HCL SALT
90347YTW5F
塩酸アルフゾシン
Title: Alfuzosin
CAS Registry Number: 81403-80-7
CAS Name: N-[3-[(4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarboxamide
Additional Names: N1-(4-amino-6,7-dimethoxyquinazol-2-yl)-N1-methyl-N2-(tetrahydrofuroyl-2)-propylenediamine
Manufacturers’ Codes: SL-77.499
Molecular Formula: C19H27N5O4
Molecular Weight: 389.45
Percent Composition: C 58.60%, H 6.99%, N 17.98%, O 16.43%
Literature References: a1-Adrenoceptor antagonist structurally similar to prazosin, q.v. Prepn: P. M. J. Manoury, DE 2904445idem, US 4315007 (1979, 1982 both to Synthelabo); and antihypertensive activity in rats: P. M. Manoury et al., J. Med. Chem. 29,19 (1986). Pharmacology: A. G. Ramage, Eur. J. Pharmacol. 129, 307 (1986). HPLC determn in biological fluids: P. Guinebault et al., J. Chromatogr. 353, 361 (1986). Pharmacology in humans: A. H. Deering, Br. J. Clin. Pharmacol. 25, 417 (1988). Clinical evaluation in essential hypertension: S. Leto Di Priolo et al., Eur. J. Clin. Pharmacol. 35, 25 (1988); A. K. Ghosh, S. Ghosh, Ger. Cardiovasc. Med. 1, 81 (1988). Clinical trial in benign prostatic hyperplasia (BPH): C. G. Roehrborn et al., BJU Int. 92, 257 (2003). Review of clinical experience in BPH: D. M. Weiner, F. C. Lowe, Expert Opin. Pharmacother. 4, 2057-2063 (2003).
Alfuzosin hydrochloride: sc-203812...

Alfuzosin hydrochloride (CAS 81403-68-1)

Derivative Type: Hydrochloride
CAS Registry Number: 81403-68-1
Manufacturers’ Codes: SL-77.499-10
Trademarks: Mittoval (Schering AG); Urion (Zambon); UroXatral (Sanofi-Synthelabo); Xatral (Sanofi-Synthelabo)
Molecular Formula: C19H27N5O4.HCl
Molecular Weight: 425.91
Percent Composition: C 53.58%, H 6.63%, N 16.44%, O 15.03%, Cl 8.32%
Properties: Crystals from ethanol + ether, mp 225° (Manoury, 1986), also reported earlier as mp 235° (dec) (Manoury, 1982). pKa 8.13.
Melting point: mp 225° (Manoury, 1986); mp 235° (dec) (Manoury, 1982)
pKa: pKa 8.13
Therap-Cat: Antihypertensive. In treatment of benign prostatic hypertrophy.
Keywords: Antihypertensive; Quinazoline Derivatives; Antiprostatic Hypertrophy; a-Adrenergic Blocker.

Alfuzosin (INN, provided as the hydrochloride salt) is a pharmaceutical drug of the α1 blocker class. As an antagonist of the α1adrenergic receptor, it works by relaxing the muscles in the prostate and bladder neck, making it easier to urinate. It is thus used to treat benign prostatic hyperplasia (BPH).[1]

Alfuzosin is marketed in the United States by Sanofi Aventis under the brand name Uroxatral and elsewhere under the tradenames Xat, Xatral, Prostetrol and Alfural. Alfuzosin was approved by the U.S. FDA for treatment of BPH in June 2003.

Side effects

The most common side effects are dizziness (due to postural hypotension), upper respiratory tract infectionheadachefatigue, and abdominal disturbances. Side effects include stomach pain, heartburn, and congested nose.[2] Adverse effects of alfuzosin are similar to that of tamsulosin with the exception of retrograde ejaculation.[3]

Contraindications

Alfuzosin should be used with caution in patients with severe renal insufficiency, and should not be prescribed to patients with a known history of QT prolongation who are taking medications known to prolong the QT interval.

Chemistry

Alfuzosin contains a stereocenter and is therefore chiral. There are two enantiomeric forms, (R)-alfuzosin and (S)-alfuzosin. The drug is used as a racemate, (RS)-alfuzosin, a 1: 1 mixture of the (R)- and (S)-forms.[4]

Enantiomers of alfuzosin
Strukturformel des (R)-Enantiomers
CAS number: 123739-69-5
Strukturformel des (S)-Enantiomers
CAS number.: 123739-70-8

Alfuzosin

    • ATC:G04CA01
  • Use:antihypertensive, α1-adrenoceptor antagonist, α-blocker, treatment of benign prostatic hypertrophy (BPH)
  • Chemical name:(±)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarboxamide
  • Formula:C19H27N5O4
  • MW:389.46 g/mol
  • CAS-RN:81403-80-7

Derivatives

monohydrochloride

  • Formula:C19H27N5O4 • HCl
  • MW:425.92 g/mol
  • CAS-RN:81403-68-1

Substance Classes

Synthesis Path

Substances Referenced in Synthesis Path

CAS-RN Formula Chemical Name CAS Index Name
23680-84-4 C10H10ClN3O2 4-amino-2-chloro-6,7-dimethoxyquinazoline 4-Quinazolinamine, 2-chloro-6,7-dimethoxy-
5004-88-6 C9H12N2O3 2-amino-4,5-dimethoxybenzamide Benzamide, 2-amino-4,5-dimethoxy-
541-41-3 C3H5ClO2 chloroformic acid ethyl ester Carbonochloridic acid, ethyl ester
72104-44-0 C9H14N2O2 2-cyano-N-methyl-N-tetrahydrofuroylethylamine 2-Furancarboxamide, N-(2-cyanoethyl)tetrahydro-N-methyl-
27631-29-4 C10H8Cl2N2O2 2,4-dichloro-6,7-dimethoxyquinazoline Quinazoline, 2,4-dichloro-6,7-dimethoxy-
28888-44-0 C10H10N2O4 2,4-dihydroxy-6,7-dimethoxyquinazoline 2,4(1H,3H)-Quinazolinedione, 6,7-dimethoxy-
20357-25-9 C9H9NO5 4,5-dimethoxy-2-nitrobenzaldehyde Benzaldehyde, 4,5-dimethoxy-2-nitro-
4959-60-8 C9H10N2O5 4,5-dimethoxy-2-nitrobenzamide Benzamide, 4,5-dimethoxy-2-nitro-
28888-44-0 C10H10N2O4 6,7-dimethoxyquinazoline-2,4-dione 2,4(1H,3H)-Quinazolinedione, 6,7-dimethoxy-
541-41-3 C3H5ClO2 ethyl chloroformate Carbonochloridic acid, ethyl ester
693-05-0 C4H8N2 3-(methylamino)propanenitrile Propanenitrile, 3-(methylamino)-
81403-67-0 C9H18N2O2 N1-methyl-N2-tetrahydrofuroyltrimethylenediamine 2-Furancarboxamide, tetrahydro-N-[3-(methylamino)propyl]-
16874-33-2 C5H8O3 (±)-tetrahydrofuran-2-carboxylic acid 2-Furancarboxylic acid, tetrahydro-
167391-50-6 C8H12O5 tetrahydro-2-furancarboxylic acid anhydride with ethyl hydrogen carbonate 2-Furancarboxylic acid, tetrahydro-, anhydride with ethyl hydrogen carbonate
57-13-6 CH4N2O urea Urea
120-14-9 C9H10O3 veratraldehyde Benzaldehyde, 3,4-dimethoxy-

Trade Names

Country Trade Name Vendor Annotation
D Alfunar Apogepha
Alfusin TAD Pharma
Urion Sanofi-Aventis
Uroxatral Sanofi-Aventis
F Urion Zambon
Xatral Sanofi-Aventis
GB Xatral Sanofi-Aventis
I Mittoval Sanofi-Aventis
Xatral Sanofi-Aventis

Formulations

  • film tabl. 2.5 mg; retard tabl. 10 mg (hydrochloride)

References

    • Manoury, P.M. et al.: J. Med. Chem. (JMCMAR) 29, 19 (1986).
    • US 4 315 007 (Synthelabo; 9.2.1982; F-prior. 6.2.1978, 29.12.1978).
    • DE 2 904 445 (Synthelabo; appl. 16.8.1979; F-prior. 6.2.1978, 29.12.1978).
  • synthesis of 6,7-dimethoxyquinazoline-2,4-dione:

    • Althuis, T.H.; Hess, H.J.: J. Med. Chem. (JMCMAR) 20, 146 (1977).

SYN

Mathias Scheer, “Alfuzosin tablets and synthesis.” U.S. Patent US20060062845, issued March 23, 2006.

US20060062845

Syn,  DOI: 10.1021/jm00151a003 NB: (WO2009001369)

Image result for alfuzosin

Image result for alfuzosin

FTIR spectrum of alfuzosin hydrochloride 

CLIP

 

Add the following:
Alfuzosin Hydrochloride
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C19H27N5O4·HCl 425.91

2-Furancarboxamide, N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-, monohydrochloride (±).
(±)-N-[3-[(4-Amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furamide monohydrochloride [81403-68-1].
» Alfuzosin Hydrochloride contains not less than 99.0 percent and not more than 101.0 percent of C19H27N5O4·HCl, calculated on the anhydrous basis.
Packaging and storage— Preserve in tight, well-closed containers, protected from light and humidity. Store at room temperature.

Identification—

B: It meets the requirements of the test for Chloride 191.

pH 791between 4.0 and 5.5

Test solution: 20 mg per mL, in carbon dioxide-free water.

Optical rotation 7810.10 to +0.10

Test solution: 20 mg per mL, in carbon dioxide-free water.
Water, Method I 921not more than 0.5%.
Residue on ignition 281not more than 0.1%.

Related compounds—

Solution A— Dilute 5.0 mL of perchloric acid in 900 mL of water, adjust with 2 M sodium hydroxide solution to a pH of 3.5, and dilute with water to 1000 mL.
Mobile phase— Prepare a filtered and degassed mixture of Solution A, acetonitrile, and tetrahydrofuran (80:20:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— Dissolve an accurately weighed quantity of USP Alfuzosin System Suitability Mixture RS in Mobile phase, and dilute quantitatively with Mobile phase to obtain a solution containing about 0.4 mg per mL.
Test solution— Dissolve 40.0 mg of Alfuzosin Hydrochloride in Mobile phase, and dilute with Mobile phase to 100.0 mL.
Reference solution— Quantitatively dilute an accurately measured volume of the Test solution by a factor of 1000 with Mobile phase.

Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a detector set at 254 nm and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the peak-to-valley ratio is at least 5. [NOTE—The peak-to-valley ratio is determined as the ratio of the height above the baseline of the impurity A peak to the height above the baseline of the lowest point of the curve separating this impurity peak from the peak due to alfuzosin.]

Procedure— Separately inject equal volumes (about 10 µL) of the Reference solution and the Test solution, record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity in the portion of Alfuzosin Hydrochloride taken by the formula:

100[r/ (1000 rS)]

in which 100 is the percentage conversion factor; rU is the peak response for any impurity obtained from the Test solution; 1000 is the dilution factor; and rS is the peak response for alfuzosin obtained from the Reference solution: the limits are as shown in the accompanying table. Disregard any peak with an area less than 0.05%.

Compound Relative 
Retention Time
Limit 
(%)
Alfuzosin 1.0
Impurity A1 1.2 *
Impurity D2 0.5 0.20
Any individual unspecified impurity 0.10
Total impurities 0.30
1  N-[3-[(4-Amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino]propyl]furan-2-carboxamide.
2  N-(4-Amino-6,7-dimethoxyquinazolin-2-yl)-N-methylpropane-1,3-diamine.
*  Impurity A, a component of USP Alfuzosin System Suitability Mixture RS, is not a specified impurity.
Assay— Dissolve about 300 mg of Alfuzosin Hydrochloride, accurately weighed, in a mixture of 40 mL of anhydrous acetic acid and 40 mL of acetic anhydride. Titrate with 0.1 M perchloric acid, determining the endpoint potentiometrically. Each mL of 0.1 M perchloric acid is equivalent to 42.59 mg of C19H27N5O4·HCl.USP32

Auxiliary Information— Please check for your question in the FAQs before contacting USP.

Topic/Question Contact Expert Committee
Monograph Daniel K. Bempong, Ph.D.
Senior Scientist
1-301-816-8143
(MDPS05) Monograph Development-Pulmonary and Steroids
Reference Standards Lili Wang, Technical Services Scientist
1-301-816-8129
RSTech@usp.org
USP32–NF27 Page 1449

Pharmacopeial Forum: Volume No. 34(1) Page 69

Chromatographic Column—

Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.

References

  1. Jump up^ Lepor, Herbert (2016). “Alpha-blockers for the Treatment of Benign Prostatic Hyperplasia”Urologic Clinics of North America43 (3): 311–23. doi:10.1016/j.ucl.2016.04.009PMC 2213889Freely accessiblePMID 27476124.
  2. Jump up^ “Alfuzosin”MedlinePlusUnited States National Library of Medicine. April 15, 2016.
  3. Jump up^ Hills, Robert K; Liu, Chenli; Zeng, Guohua; Kang, Ran; Wu, Wenqi; Li, Jiasheng; Chen, Kang; Wan, Show P. (2015). “Efficacy and Safety of Alfuzosin as Medical Expulsive Therapy for Ureteral Stones: A Systematic Review and Meta-Analysis”PLOS ONE10 (8): e0134589. doi:10.1371/journal.pone.0134589ISSN 1932-6203PMC 4526635Freely accessiblePMID 26244843. This article incorporates text available under the CC BY 4.0 license.
  4. Jump up^ Rote Liste Service GmbH (Hrsg.): Rote Liste 2017 – Arzneimittelverzeichnis für Deutschland (einschließlich EU-Zulassungen und bestimmter Medizinprodukte). Rote Liste Service GmbH, Frankfurt/Main, 2017, Aufl. 57, S. 159, ISBN 978-3-946057-10-9.

External links

Alfuzosin
Alfuzosin.svg
Clinical data
Pronunciation /ælˈfjuːzsɪn/ al-FEW-zoh-sin
Trade names Uroxatral, others
AHFS/Drugs.com Monograph
MedlinePlus a64002
Pregnancy
category
  • AU: B2
  • US: B (No risk in non-human studies)
Routes of
administration
By mouth (tablets)
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 49%
Protein binding 82–90%
Metabolism Liver (CYP3A4-mediated)
Elimination half-life 10 hours
Excretion Feces (69%) and Urine (24%)
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.108.671 Edit this at Wikidata
Chemical and physical data
Formula C19H27N5O4
Molar mass 389.46 g·mol−1
3D model (JSmol)

/////////////////塩酸アルフゾシン, Uroxatral, alfuzosin

COC1=C(OC)C=C2C(N)=NC(=NC2=C1)N(C)CCCNC(=O)C1CCCO1

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DR ANTHONY CRASTO

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 30 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, Dr T.V. Radhakrishnan and Dr B. K. Kulkarni, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 30 year tenure till date Dec 2017, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 50 Lakh plus views on dozen plus blogs, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 19 lakh plus views on New Drug Approvals Blog in 216 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc

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