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Levalfuzosin, preparation method and use thereof

A technology of dextroalfuzosin and alfuzosin, which is applied in the field of preparation of drugs for the specific treatment of benign prostatic hyperplasia, optically active levofuzosin and its salt and its slow-release preparations

Inactive Publication Date: 2009-04-01
RENHE YIKANG MEDICINE TECH TIANJIN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Although (±) alfuzosin as selective alpha 1 Receptor blockers can relieve the symptoms of BPH urinary tract obstruction, but they are found to have very significant cardiovascular side effects, such as hypotension, dizziness, headache, dry mouth, restlessness, nervousness, sweating, tachycardia and Skin flushing, etc. (Wilde MI, Fitton A, Me Tavish D. Alfuzosin. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in benign prostatic hyperplasia. Drugs, 1993, 45(3): 410~29; Lepor H, Knapp-Maloney G, Sunshine H. A dose titration study evaluating terazosin, a selective, once-a-dayα 1 -blocker for the treatment of symptomatic benign prostatic hyperplasia, J Urol., 1990a, 144(6):1393~7.)

Method used

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  • Levalfuzosin, preparation method and use thereof
  • Levalfuzosin, preparation method and use thereof
  • Levalfuzosin, preparation method and use thereof

Examples

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preparation example Construction

[0027] The preparation method of L-alfuzosin of the present invention is introduced below.

[0028] The levo-alfuzosin of the present invention can be carried out by conventional optical resolution methods. For example, it can be carried out by resolving the commercially available racemic alfuzosin (hereinafter referred to as (±) alfuzosin), first salting the commercially available (±) alfuzosin, and then chromatographically Alternatively, fractional crystallization can be carried out to obtain L-alfuzosin.

[0029] For example, ordinary preparative chromatographic columns can be used, and conventional methods can be used for resolution according to ordinary separation methods, such as adding chiral additives to the mobile phase, and through the interaction between the chiral additives and the racemic alfuzosin to be separated , so that (-) alfuzosin and (+) alfuzosin have different retention times, thereby achieving separation. Afterwards, the chiral additive is removed to ...

preparation example 1

[0052] Preparation Example 1 Preparation of N-(4-amino-6,7-dimethoxyquinazolinyl)-N-methylpropylenediamine (IV)

[0053]

[0054] In 200 milliliters of n-butanol, add 24 grams (0.1mol) of 4-amino-2-chloro-6,7-dimethoxyquinazoline and 16.6 grams (0.2mol) of 3-methylaminopropionitrile and reflux 5 hours, cooled and filtered, washed with ethanol, and dried to a weight of 30.7 grams, with a yield of 95%.

[0055] In a 500 ml autoclave, add 250 ml of 15% ethanol ammonia solution, 11.5 g of the above product, add 0.5 g of Raney nickel, 80 kg of pressure, react at 80 ° C for 6 hours, filter the catalyst, evaporate the solvent to dryness, add concentrated hydrochloric acid for 15 After 1 ml, evaporate to dryness and recrystallize with isopropanol to obtain 6.7 g of N-(4-amino-6,7-dimethoxyquinazolinyl)-N-methylpropanediamine hydrochloride, melting point 270°C .

preparation example 2

[0056] Preparation Example 2 Preparation of Levo-Alfuzosin Hydrochloride

[0057] At room temperature, stir dropwise 40 ml of thionyl chloride to 25 ml of S-(-)-tetrahydrofuran-2-carboxylic acid [α] D 20 =+19 (pure product), after reacting for 4 hours, reflux for 30 minutes, and distill under reduced pressure to obtain 28 g of S-(-)-tetrahydrofuran-2-formyl chloride (intermediate 1), with a yield of 93.3%.

[0058] Add 6.0 g of N-(4-amino-6,7-dimethoxyquinazolinyl)-N-methylpropylenediamine hydrochloride into 100 ml of DMF, and add 5 ml of triethylamine to dissolve it. Add 2.46 g of S-(-)-tetrahydrofuran-2-formyl chloride (intermediate 1) and react at room temperature for 3 hours, add 500 ml of water, precipitate a solid, filter and wash with water, then dry to obtain 7.0 g of the product base, with a yield of 98%.

[0059] After adding 8 ml of hydrochloric acid to the base product above, evaporate to dryness and dissolve with 20 ml of absolute ethanol, add 30 ml of acetone, ...

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Abstract

The invention relates to optical-active levo-alfuzosin ((-) alfuzosin) or the salt thereof and the medicines of the levo-alfuzosin or the salt thereof containing effective curing quantity and the medical carrier and used for treating the benign prostatic hyperplasia. The invention also relates to the optical-active (plus) alfuzosin or the salt thereof and the application of the (plus) alfuzosin or the salt thereof for treating the hypertension.

Description

Technical field: [0001] The present invention relates to optically active levo-alfuzosin and various salts thereof and preparations containing the active ingredient, which can specifically act on alpha 1 receptors, while reducing the systemic effects of alfuzosin. More specifically, the present invention relates to optically active levo-alfuzosin and its salts and their slow-release preparations and their use in the preparation of drugs for the specific treatment of benign prostatic hyperplasia. Background technique: [0002] Benign prostatic hyperplasia (benign prostatic hyperplasia, BPH) is one of the common and frequently occurring diseases of middle-aged and elderly men. Its incidence increases with age. The prolongation of the average human life expectancy, the number of its incidence is also increasing day by day. BPH is currently mostly treated with surgery. Although the effect is good, the symptoms of 20% of patients with surgery cannot be fundamentally relieved; ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D405/12A61K31/517A61P13/08A61P9/12
Inventor 牛长群刘庆彬任雷鸣
Owner RENHE YIKANG MEDICINE TECH TIANJIN
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