81403-68-1 Usage
Description
Alfuzosin (SL-77499) (I), a quinazoline derivative which
is a uroselective alpha-1 adrenoreceptor antagonist, has been
developed and launched worldwide by Sanofi-Synthelabo,
for the treatment of benign prostate hyperplasia (BPH).
In November 2003, alfuzosin (I) was launched as an
extended release formulation in the US as Uroxatral utilizing
Skyepharma’s oral controlled release technology.
Chemical Properties
White to Off-White Solid
Uses
Different sources of media describe the Uses of 81403-68-1 differently. You can refer to the following data:
1. a-1- Adrenoceptor antagonist structurally similar to prozosin
2. Antihypertensor;Alpha 1- adrenergic antagonist
3. α1-Adrenoceptor antagonist structurally similar to Prozosin. Antihypertensive. Alfuzosin hydrochloride is used in treatment of benign prostatic hypertrophy.
Brand name
Uroxatral (Sanofi Aventis).
General Description
Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.
Biological Activity
Functionally uro-selective α 1 adrenoceptor antagonist that does not discriminate between α 1 subtypes. Inhibits increases in intraurethral pressure caused by phenylephrine-induced contraction by 81% with minor cardiovascular effects. Also relaxes corpus cavernosum tissue (pIC 50 = 7.64) in vitro .
Biochem/physiol Actions
Alfuzosin hydrochloride is an alpha-adrenergic blocker used to treat benign prostatic hyperplasia (BPH). It works by relaxing the muscles in the prostate and bladder neck, making it easier to urinate.
Clinical Use
Alpha-blocker:
Treatment of benign prostatic hyperplasia
Treatment of acute urinary retention
Synthesis
Although
syntheses of alfuzosin (I) have appeared in several reports, an optimized route used for the manufacture of the compound does not appear in the literature. The synthesis
reported by the Sanofi group for alfuzosin will be described
and is shown in the scheme. The commercially available 4-
amino-2-chloro-6,7-dimethoxyquinazoline (1) was treated
with 3-methylaminopropionitrile (2) in isoamyl alcohol and
refluxed for 5 hrs. Filtration of the precipitated product and
washing with ethanol gave nitrile 3 in 62% yield.
Hydrogenation of the nitrile was done in 15% ammonia
solution in ethanol with Raney nickel as catalyst at 70°C
and 1000 psi to obtain the corresponding amine free base.
Conversion of the free base to the hydrochloride salt was
done in ethanol to give the HCl salt 4 in 52% yield. The
final acylation of amine 4 was done with the imidazolyl
anhydride of furan 5. Thus, 2-carboxyfuran was treated with
carbonyldiimidazole in THF at 40°C for 1 hr and then
cooled to 10°C. Addition of amine 4 in THF in the presence
of triethylamine at 10°C, then refluxing the reaction for 1 hr,
and aqueous workup gave the alfuzosin free base. After
conversion to the hydrochloride salt and recrystallization
from 2-propanol alfuzosin hydrochloride (I) was obtained in
44% yield.
Drug interactions
Potentially hazardous interactions with other drugs
Anaesthetics: enhanced hypotensive effect.
Antidepressants: enhanced hypotensive effect with
MAOIs.
Antivirals: concentration possibly increased by
ritonavir - avoid; avoid with telaprevir.
Avanafil, vardenafil, sildenafil and tadalafil: enhanced
hypotensive effect, separate administration by 4-6
hours.
Beta-blockers: enhanced hypotensive effect;
increased risk of first dose hypotensive effect.
Calcium-channel blockers: enhanced hypotensive
effect; increased risk of first dose hypotensive effect.
Cobicistat: concentration of alfuzosin possibly
increased - avoid.
Diuretics: enhanced hypotensive effect; increased
risk of first dose hypotensive effect.
Moxisylyte: possibly severe postural hypotension.
Metabolism
Extensively metabolised in the liver, mainly by the
cytochrome P450 isoenzyme CYP3A4, to inactive
metabolites that are mainly excreted in faeces via the bile.
Check Digit Verification of cas no
The CAS Registry Mumber 81403-68-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,1,4,0 and 3 respectively; the second part has 2 digits, 6 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 81403-68:
(7*8)+(6*1)+(5*4)+(4*0)+(3*3)+(2*6)+(1*8)=111
111 % 10 = 1
So 81403-68-1 is a valid CAS Registry Number.
InChI:InChI=1/C19H27N5O4.ClH/c1-24(8-5-7-21-18(25)14-6-4-9-28-14)19-22-13-11-16(27-3)15(26-2)10-12(13)17(20)23-19;/h10-11,14H,4-9H2,1-3H3,(H,21,25)(H2,20,22,23);1H
81403-68-1Relevant articles and documents
Improved method used for preparing quinazoline drugs
-
, (2018/07/06)
The invention relates to an improved method used for preparing quinazoline drugs, and provides a synthesis route taking 2-chloro-4-amino-6,7-dimethoxyquinazoline as an intermediate. The synthesis route comprises following steps: acrylonitrile and a methylamine alcohol solution are subjected to amination reaction so as to obtain intermediate (I); triethylamine is taken as an acid binding agent, andbenzyl chloride is taken as a protective group so as to obtain an intermediate (II); a metal hydride is adopted so as to obtain an intermediate (III) through reduction; acylation with tetrahydro-2-furancarbonylchloride is carried out so as to obtain an intermediate (IV); the intermediate (IV) and ammonium formate are subjected to hydrogenolysis under catalytic effect of palladium on carbon so asto obtain an intermediate (V); and at least condensation reaction with 2-chloro-4-amino-6,7-dimethoxyquinazoline is carried out so as to obtain quinazoline drug Alfuzosin Hydrochloride (VI). Comparedwith the prior art, the improved method possesses following advantages: operation is simple and safe; reaction conditions are convenient to control; energy consumption is low; yield is stable; and industrialized application prospect is promising.
METHOD OF PREPARING ANHYDROUS ALFUSOZIN HYDROCHLORIDE
-
Page/Page column 13; 14, (2010/04/03)
There is described a method of preparing anhydrous alfuzosin hydrochloride by means of a condensation reaction between N1-methyl-N2-(tetrahydrodrofuroyl-2)-propylenediamine and 4-amino-2-chloro-6,7-dimethoxyquinazoline. The obtained crude product is subsequently purified by further stages that include steps of preparing novel intermediates. The described alfuzosin synthesis and purification process allow to obtain this active ingredient with a high yield and purity, and therefore suitable to be employed as an active ingredient in medicaments.
AN IMPROVED PROCESS FOR THE PREPARATION OF ALFUZOSIN AND ITS NOVEL POLYMORPH
-
Page/Page column 10, (2009/03/07)
The present invention relates to an improved process for the preparation of Alfuzosin of formula (I). The process involves utilizing intermediate of formula (Ia) wherein S represents acid residue of organic acids like acetic acid, oxalic acid, succinic acid, methane sulfonic acid, p-toluene sulfonic acid and the like. The present invention also relates to novel Amorphous form of Alfuzosin of formula (I).
