Acid addition salt of optically active dihydropyridine derivative

A dihydrobromide, dihydrochloride technology, applied in the treatment or prevention of hypertension or heart disease, or kidney damage, treatment or prevention of hypertension. , Most preferred for hypertension, more preferred in the field of hypertension or heart disease, can solve problems such as unknown acid addition salts

Inactive Publication Date: 2008-12-03
UBE IND LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, it is not known so far that an acid addition salt of compound (I) can be obtained as a crystalline solid

Method used

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  • Acid addition salt of optically active dihydropyridine derivative
  • Acid addition salt of optically active dihydropyridine derivative
  • Acid addition salt of optically active dihydropyridine derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0107] (Example 1) (R)-2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-(1-di Phenylmethylazetidine-3-yl) ester 5-isopropyl ester dihydrochloride dihydrate

[0108]In (R)-2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-(1-diphenylmethyl To a 240 ml ethyl acetate solution of 8.74 g (15.0 mmol) of azetidin-3-yl) ester 5-isopropyl ester, 2.57 ml (30.0 mmol) of 36 wt% hydrochloric acid was added dropwise at 25°C over 30 minutes. After the dropwise addition, the reaction solution was further stirred for 30 minutes. The resulting crude crystals were filtered, washed with 15 ml of ethyl acetate, and dried under reduced pressure at 50° C. for 2 hours to obtain 9.20 g (89%) of the target compound as a white powder.

[0109] 1 H-NMR spectrum (DMSO-d 6 , Δppm): 0.99 (d; J = 6Hz, 3H), 1.19 (dd; J = 6Hz, 3Hz, 3H), 2.29 (s, 3H), 4.03-4.27 (m, 4H), 4.73-4.90 (m, 2H), 4.93-5.31 (m, 1H), 5.68-6.00 (m, 1H), 6.94 (brs, 2H), 7.33-7.74 (m, 1...

Embodiment 2

[0112] (Example 2) (R)-2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-(1-di Phenylmethylazetidine-3-yl) ester 5-isopropyl ester dihydrobromide dihydrate

[0113] (2A) [Reaction solvent: acetone]

[0114] In (R)-2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-(1-diphenylmethyl To a solution of 2.91 g (5.00 mmol) of azetidine-3-yl) ester 5-isopropyl ester in 7 ml of acetone, 1.16 ml (10.0 mmol) of 47 wt% hydrobromic acid was added dropwise at 25°C over 30 minutes. After the dropwise addition, the reaction solution was further stirred for 30 minutes. The resulting crude crystals were filtered, washed with 7 ml of acetone, and dried at 60° C. under reduced pressure for 2 hours to obtain 2.68 g (69%) of the target compound as a white powder.

[0115] 1 H-NMR spectrum (DMSO-d 6 , Δppm): 0.99(d; J=6Hz, 3H), 1.19(d; J=6Hz, 3H), 2.29(s, 3H), 4.01-4.38(m, 4H), 4.75-4.89(m, 2H) , 4.96-5.23 (m, 1H), 5.78-6.08 (m, 1H), 6.85 (brs, 2...

preparation example 1

[0200] (Preparation Example 1) Capsules

[0201] The powders of the compound of Example (10.0 mg), lactose (168.7 mg), corn starch (70.0 mg) and magnesium stearate (1.3 mg) (250 mg in total) were mixed, and after passing through a 60-mesh sieve, the powder was placed in No. 2 As a capsule in gelatin capsules.

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Abstract

An excellent medicine for the treatment or prevention of hypertension or the like is provided. A specific acid addition salt of (R)-2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5- pyridinedicarboxylic acid 3-(1-diphenylmethylazetidin-3- yl)ester 5-isopropyl ester is useful as a medicine for the treatment or prevention of hypertension or the like.

Description

Technical field [0001] The present invention relates to (R)-2- which exhibits excellent calcium antagonistic effect, blood pressure lowering effect, vasodilator effect, cardioprotective effect, anti-arteriosclerosis effect, diuretic effect, renal damage inhibitory effect, and effect of hindering the production of lipid peroxide Amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3-(1-diphenylmethylazetidine-3 -The specific acid addition salt of 5-isopropyl ester. [0002] The present invention relates to a pharmaceutical composition containing (R)-2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 3- The specific acid addition salt of (1-diphenylmethylazetidin-3-yl) ester 5-isopropyl ester as an active ingredient is preferably used for the treatment or prevention of hypertension, heart disease, and arteriosclerosis It is more preferably used to treat or prevent hypertension or heart disease; it is most preferably used to treat or pr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/12A61P9/10A61K31/4427A61P9/12A61P9/04A61P13/12
CPCC07D401/12A61P7/10A61P9/04A61P9/08A61P9/10A61P9/12A61P13/12A61K31/4427C07D403/12
Inventor 萩原昌彦清水基久小林克弘吉江泰志
Owner UBE IND LTD
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