Arylsubstituted piperazines useful in the threatement of bening prostatic hyperlasia

A technology of piperazine and substituent, applied in the field of aryl-substituted piperazine, can solve problems such as clinical side effects

Inactive Publication Date: 2000-08-23
ORTHO MCNEIL PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although α1-AR blockers are well tolerated, about 10-15% of patients have clinical side effects after medication (Lepor, 1995)

Method used

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  • Arylsubstituted piperazines useful in the threatement of bening prostatic hyperlasia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] 1-(2-phthalimidoethyl)-4-(2-isopropoxyphenyl)piperazine

[0036] Compound 1

[0037] N-(2-bromoethyl)phthalimide (7.6g, 30mmol) and K 2 CO 3 (6.2g, 45mmol) was added to a solution of N-1-(2-isopropoxyphenyl)piperazine (6.6g, 30mmol) in acetonitrile (100ml), and the resulting mixture was heated to reflux for 2 days. The mixture was concentrated in vacuo and purified by column chromatography on silica gel with EtOAc / hexanes (30:70) as eluent to afford the title compound as a solid: MS m / z 394 (MH + ).

Embodiment 2

[0039] 1-(2-aminoethyl)-4-(2-2-isopropoxyphenyl)piperazine

[0040] Compound 2

[0041] A solution of compound 1 (7.5 g, 19 mmol) in EtOH (70 ml) was stirred at room temperature for 10 min. Methylhydrazine (20ml) was added and the mixture was heated to reflux for 2.5 hours. The mixture was cooled to room temperature and the resulting solid precipitate was removed by filtration. The precipitate was concentrated in vacuo to give the title compound as a solid: MS m / z 264 (MH + ), the compound was used without purification.

Embodiment 3

[0043] 1-tert-butoxycarbonylmethyl-2-piperidone

[0044] Compound 3

[0045] 95% sodium hydride (1.67g, 66mmol) was added to a solution of δ-valerolactam (5.95g, 60mmol) in toluene (100ml) under stirring at 0°C, and the resulting suspension was stirred for 1 hour. Tert-butyl bromoacetate (8.86ml, 60mmol) was added dropwise and the reaction mixture was allowed to warm to room temperature and stirred for 10 hours. Add saturated NH 4Cl aqueous solution, the obtained organic layer was successively washed with brine and water successively. The combined organic layers were dried (Na 2 SO 4 ) and concentrated in vacuo to afford compound 3 as an oil.

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Abstract

This invention relates to a series of arylsubstituted piperazines, of Formula I pharmaceutical compositions containing them and intermediates used in their manufacture. The compounds of the invention selectively inhibit binding to the alpha-1a adrenergic receptor, a receptor which has been implicated in benign prostatic hyperplasia. As such the compounds are potentially useful in the treatment of this and other disease.

Description

[0001] The present invention relates to a series of aryl-substituted piperazines, pharmaceutical compositions containing them, and intermediates for their preparation. The compounds of the present invention selectively inhibit the expression of alpha-1 enzymes involved in benign prostatic hypertrophy a Binding of adrenergic receptors. In addition, compounds of the present invention are capable of reducing intraurethral pressure in an in vivo model. Accordingly, the compounds of the present invention are useful in the treatment of benign prostatic hypertrophy. Background technique [0002] Benign prostatic hypertrophy (BPH), a benign enlargement of the prostate gland, is the most common benign tumor in men. About 50% of men over the age of 65 suffer from varying degrees of BPH, and one-third of these men have clinical symptoms consistent with bladder outlet obstruction (Hieble and Caine, 1986). In the United States, men over the age of 50 are respons...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/12A61K31/397A61K31/40A61K31/4015A61K31/402A61K31/4025A61K31/445A61K31/496A61K31/55A61P13/08C07D205/08C07D207/12C07D207/26C07D207/27C07D207/28C07D209/44C07D209/48C07D211/40C07D211/76C07D221/20C07D223/10C07D225/02C07D225/08C07D241/04C07D295/08C07D295/13C07D401/12C07D403/12
CPCC07D209/48C07D223/10C07D211/76C07D207/28C07D207/27C07D295/13A61P13/08A61P43/00A61K31/33
Inventor L·乔利夫W·默累V·普利托A·雷茨李晓冰L·穆尔卡希C·马亚诺夫F·维拉尼
Owner ORTHO MCNEIL PHARM INC
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