Amidophenyl-1,3,4-oxadiazole compound and its preparation method and use

An amide phenyl and oxadiazole technology, applied in the field of medicine, can solve the problems of limited types of compounds, poor activity and bioavailability, etc., and achieve the effects of good druggability, reducing the risk of side effects, and improving water solubility

Inactive Publication Date: 2014-10-15
EAST CHINA NORMAL UNIV +1
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the types of compounds reported are limited, and no drugs have entered clinical research due to problems such as poor activity and bioavailability

Method used

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  • Amidophenyl-1,3,4-oxadiazole compound and its preparation method and use
  • Amidophenyl-1,3,4-oxadiazole compound and its preparation method and use
  • Amidophenyl-1,3,4-oxadiazole compound and its preparation method and use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Embodiment 1 Compound I of the present invention (R 1 = Me, n = 4, R 2 =OH) Preparation

[0027] The 4-substituted benzoic acid (R 1 = Me or NMe 2 ) is condensed with m-nitrobenzoic acid, dehydrated and ring-closed by phosphorus oxychloride, and then the nitro group is reduced to obtain compound II (R 1 = Me or NMe 2 ). Compound II (R) in the present invention and its various embodiments 1 = Me or NMe 2 ) is detailed in the Chinese patent application (Chinese Patent Application No. 201210405000.0).

[0028] Compound II (R 1 =Me, 0.25g, 1mmol), EDC (0.4g), HOBt (0.3g), 3-methylpyridine (0.3mL), 5-hydroxyn-pentanoic acid (1mmol) and DCM (10mL) were reacted with stirring at room temperature 24h, add DCM (20mL) and methanol (8mL) to dilute the reaction solution, followed by 5% hydrochloric acid, 5% NaOH and NaHCO 3 The solution was washed, the organic phase was collected, dried over anhydrous sodium sulfate and separated by column chromatography (DCM / MeOH=20 / 1), t...

Embodiment 2

[0029] Example 2 Compound I (R 1 = Me, n = 7, R 2 =OH) Preparation

[0030] Referring to the method shown in Example 1, wherein "5-hydroxy-n-pentanoic acid" is replaced by 7-hydroxyoctanoic acid. White solid; Yield: 33%. 1 H NMR (500MHz, DMSO-d 6 )δ1.23~1.25(m, 6H), 1.39~1.42(m, 2H), 1.60~1.62(m, 2H), 2.34(t, J=7.3Hz, 2H), 2.40(s, 3H), 3.35 ~3.37(m, 2H), 4.37(t, J=5.3Hz, 1H), 7.43(d, J=7.8Hz, 2H), 7.53(t, J=7.7Hz, 1H), 7.76(d, J=7.7Hz, 1H), 7.76(d, J=7.8Hz, 1H) 7.7Hz, 1H), 7.80(d, J=7.7Hz, 1H), 7.97(d, J=7.8Hz, 2H), 8.44(s, 1H), 10.19(s, 1H); 13 C NMR (125MHz, DMSO-d 6 )δ 171.8, 164.1, 163.8, 142.2, 140.2, 130.0 (2C), 129.9, 126.6 (2C), 123.7, 122.1, 121.1, 120.6, 116.6, 60.7, 36.5, 32.5, 28.7, 28.7, 25.4, 22.0, 21. ; HRMS (ESI): Calcd for C 23 h 28 N 3 o 3 [M+H] + , 394.2125; Found, 394.2185.

Embodiment 3

[0031] Embodiment 3 compound I (R 1 = Me, n = 3, R 2 = COOMe) preparation

[0032] Compound II (R 1 = A mixture of Me, 0.25 g, 1 mmol), EDC (0.4 g), HOBt (0.3 g), 3-picoline (0.3 mL), monomethyl succinate (1 mmol) and DCM (10 mL) was stirred at room temperature Reacted for 24h, added DCM (20mL) and methanol (8mL) to dilute the reaction solution, followed by 5% hydrochloric acid, 5% NaOH and NaHCO 3 The solution was washed, and the organic phase was collected, dried over anhydrous sodium sulfate and separated by column chromatography ((DCM / EA=10 / 1) to obtain the product I (R 1 = Me, n = 3, R 2 =COOMe) 0.18g. White solid; Yield: 50%. 1 H NMR (400MHz, CDCl 3 )δ2.04~2.11(m, 2H), 2.39(s, 3H), 2.45(t, J=7.3Hz, 2H), 2.54(t, J=7.3Hz, 2H), 3.65(s, 3H), 7.26(d, J=8.0Hz, 2H), 7.41(t, J=8.0Hz, 1H), 7.79(d, J=7.8Hz, 1H), 7.88(d, J=7.8Hz, 1H), 7.93( d, J=8.0Hz, 2H), 8.33(s, 1H), 8.81(s, 1H); 13 C NMR (100MHz, CDCl 3 )δ 173.6, 171.2, 164.7, 164.1, 142.3, 139.1, 129.7(2C), 129.6, 1...

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Abstract

The invention discloses an amidophenyl-1,3,4-oxadiazole compound shown in the formula (I). The invention also discloses a preparation method of the amidophenyl-1,3,4-oxadiazole compound. The preparation method comprises that an amino-compound II and a substituted aliphatic acid III are condensed to form the amidophenyl-1,3,4-oxadiazole compound. The invention also discloses a use of the amidophenyl-1,3,4-oxadiazole compound I in preparation of a drug for treating type II diabetes. The amidophenyl-1,3,4-oxadiazole compound has a non-AMP structure type, can reduce side-effect risk, can obviously inhibit FBPase in a molecule level, can substantially inhibit glucose generation in a cell level, and has good cell viability and good druggability.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to amide phenyl-1,3,4-oxadiazole compounds, a preparation method and application thereof. Background technique [0002] Diabetes is a chronic disease that occurs when the pancreas does not produce enough insulin or the body cannot effectively use the insulin it produces. The World Health Organization (WHO) estimates that approximately 285 million people worldwide currently suffer from diabetes. This figure is likely to more than double by 2030. Ninety percent of diabetics around the world have type 2 diabetes, which is the result of the body's inability to use insulin effectively. [0003] Due to different causes, diabetes can be divided into four types, namely: type I, type II, gestational diabetes and other types. Among them, patients with type II diabetes account for more than 90%. It is characterized by insulin resistance (i.e. decreased sensitivity of tissues in the body to ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D271/107A61K31/4245A61K31/5377A61K31/496A61P3/10
CPCC07D271/107
Inventor 汤杰杨玲玲李佳何海兵李静雅杨帆高立信阿卜杜拉·玉苏普何亚慧
Owner EAST CHINA NORMAL UNIV
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