81403-80-7

Usage

Uses

Used in Pharmaceutical Industry:
Alfuzosin is used as a therapeutic agent for the symptomatic treatment of benign prostatic hypertrophy (BPH) and acute adenoma. It works by lowering urethral contractions induced by alpha1 stimulation, providing relief from BPH symptoms.
Alfuzosin is also being developed as an antihypertensive agent, with its efficacy in this indication being comparable to prazosin without causing significant changes in heart rate.

Therapeutic drugs for benign prostatic hyperplasia and hypertension

Benign prostatic hyperplasia (BPH) is a common disease in medium-elderly men. Prostatic hyperplasias obstruct urine excretion, which can cause irritant and obstructive urethral symptoms. The most common symptoms are nocturia, increased urgency during the day, frequent micturition, and urinary rheology. Many men over 70 years old have moderate or severe urethral symptoms due to BPH. Although BPH itself rarely endangers life, it can cause irreversible damage to the bladder or kidney if not treated. Acute urinary retention is the most serious complication of BPH. Its clinical features are sudden inability to urinate and pain. If not treated in time, it can endanger life. Alfuzosin is a selective alpha 1 receptor blocker, which belongs to the quinazoline derivative. By relaxing the tension of the urethra smooth muscle around the prostate, bladder neck and prostate, it can reduce the resistance of the urine flow, so that the symptoms such as urethral tension, resistance and pressure increase, bladder outlet obstruction and other symptoms related to prostatic hypertrophy can be alleviated. It has a quick effect and has little effect on the cardiovascular system, and there are no other adverse effects on sexual function like other annoying BPH drugs. The absorption of alfuzosin is good. The concentration of blood drug reaches peak 0.5-3 hours after taking, and the bioavailability is 64%. In the range of treatment dose, the pharmacokinetics is linear. About 87% of the drugs absorbed are combined with plasma protein. This product is mainly eliminated by liver metabolism.75%-91% of the inactive metabolite is excreted by the feces through the bile, and 15%-30% is excreted in the urine. Another 11% is excreted in the original form in the urine. The half-life of the elimination is 4-8 hours. Its pharmacokinetic characteristics are not affected by the meal. In the elderly over 75 years of age, this product is absorbed faster and the concentration of the blood drug peak is higher. In addition, AUC is also higher than the young, but the volume of distribution can be reduced and the half-life will be eliminated. In renal insufficiency, it pharmacokinetic characteristics have no obvious change. In the patients with liver dysfunction, the concentration of blood drug peak, the elimination half life and the AUC value are all increased, and the free fraction is also increased. In addition, alfuzosin is similar to proposing and palavering in function. It not only blocks the alpha 1 receptor, but also smooths diastolic blood vessel muscle, so it has good antihypertensive effect. For high blood pressure, 7.5 to 10mg should be taken for 1 day 3 times daily. It should be noticed that alfuzosin hydrochloride cannot be used with calcium antagonist and alpha blocker.

Originator

Synthelabo (France)

InChI:InChI=1/C19H27N5O4/c1-24(8-5-7-21-18(25)14-6-4-9-28-14)19-22-11-12-13(23-19)10-15(26-2)17(27-3)16(12)20/h10-11,14H,4-9,20H2,1-3H3,(H,21,25)

Upstream product

• 76362-29-3 N¹-methyl-N¹-(4-amino-6,7-dimethoxy-2-quinazolinyl)-1,3-propanediamine 
• 52449-98-6 tetrahydrofuran-2-carbonyl chloride 
• 81403-68-1 alfuzosin hydrochloride 
• 81403-67-0 N-<3-(methylamino)propyl>tetrahydrofuran-2-carboxamide 
• 23680-84-4 2-chloro-6,7-dimethoxyquinazolin-4-amine 
• 16874-33-2 tetrahydro-2-furancarboxylic acid 
• 81403-69-2 N¹-methyl-N¹-(4-amino-6,7-dimethoxy-2-quinazolinyl)-1,3-propanediamine hydrochloride 
• 1005197-73-8 1-(tetrahydrofuran-2-ylcarbonyl)-1H-imidazole 
• 1100050-87-0 (R,S)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarboxamide acetate 
• 167391-50-6 C₈H₁₂O₅ 

Downstream Products

• 81403-68-1 alfuzosin hydrochloride 

Relevant academic research and scientific papers

Chemoselective calcium-catalysed direct amidation of carboxylic esters

Unactivated carboxylic esters and primary amines undergo calcium-catalysed direct amide bond formation in excellent yields under homogeneous conditions in toluene. This green and mild reaction proceeds chemoselectively with esters, whereas related carboxylic acids and amides remain unreactive.

METHOD OF PREPARING ANHYDROUS ALFUSOZIN HYDROCHLORIDE

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.

PROCESS FOR THE PREPARATION OF ALFUZOSIN AND SALTS THEREOF

The present invention relates to novel N-[3-[(4-acyl-/aroyl-substituted amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydro-2-furancarboxamide derivatives, and a process for the preparation thereof. The novel compounds are useful for preparing alfuzosin or a pharmaceutically acceptable salt thereof in high yield and purity.

AN IMPROVED PROCESS FOR THE PREPARATION OF ALFUZOSIN AND ITS NOVEL POLYMORPH

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).

PROCESS FOR PREPARING ALFUZOSIN

Processes for preparing alfuzosin and pharmaceutically acceptable salts, solvates, hydrates thereof are disclosed. The present invention also discloses processes for preparation of anhydrous alfuzosin hydrochloride having substantially free from other pseudopolymorphic crystalline forms particularly dihydrate form of alfuzosin hydrochloride.

A NOVEL PROCESS FOR THE PREPARATION OF 2-HALO-4-AMINOQUINAZOLINES

2-Halo-4-aminoquinazolines are produced by a one-step process involving intramolecular cyclization of appropriately substituted formamide derivatives in the presence of phosphorous oxyhalides. Exemplary of the process is the intramolecular cyclization of 3,4-dimethoxy-6-cyanoaniline-1-yl formamide in the presence of phosphorous oxychloride to 2-chloro-4-amino-6,7-dimethoxyquinazoline. These chemical compounds are utilized as intermediates in the preparation of some of the important antihypertensive agents e.g. 2-chloro-4-amino-6,7-dimethoxyquinazolines is used for the synthesis of alfuzosin hydrochloride.

AN IMPROVED PROCESS FOR THE PREPARATION OF ALFUZOSIN HYDROCHLORIDE

The present invention relates to an improved process for the preparation of Alfuzosin hydrochloride of formula (I) by reacting N-(3-aminopropyl)-6,7-dimethoxy-N-methylquinazoline-2,4-diamine of Formula (II) with 1-(tetrahydrofuran-2-ylcarbonyl)-1H-imidazole of formula (IV) using acetonitrile as an organic solvent. This invention also relates to a method for the purification of N-(3-aminopropyl)-6,7-dimethoxy-N-methylquinazoline-2,4-diamine of formula (II), which is a key starting material of Alfuzosin hydrochloride by making its corresponding salt of formula (III) using an organic di-carboxylic acid in an alcoholic solvent wherein, A is denoted as a corresponding moiety of organic di-carboxylic acid.

PROCESS FOR THE PREPARATION OF ALFUZOSIN

The present invention relates to an improved process for the preparation of N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl)methylamino]propyl]tetrahydrofuran-2-carboxamide of Formula (I).

PROCESSES FOR THE PREPARATION OF ALFUZOSIN

The invention relates to processes for the preparation of alfuzosin or pharmaceutically acceptable salts thereof in high purity. More particularly, it relates to the preparation of pure crystalline alfuzosin base. The invention also relates to pharmaceutical compositions that include the pure alfuzosin or a pharmaceutically acceptable salt thereof.

PROCESS FOR THE PREPARATION OF ALFUZOSIN

The present invention relates to a simple process for the preparation of alfuzosin, it's bases and its pharmaceutically acceptable salts thereof.