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Arylpyrazole compound and application thereof

A technology of arylpyrazoles and compounds, applied in the field of chemical medicine, can solve problems such as vomiting and nausea, and achieve a good effect of inhibiting activity

Inactive Publication Date: 2020-06-02
WENZHOU PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Inhibition of the PDE4D enzyme will induce vomiting, nausea and other gastrointestinal side effects

Method used

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  • Arylpyrazole compound and application thereof
  • Arylpyrazole compound and application thereof
  • Arylpyrazole compound and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Embodiment 1: the preparation of compound a

[0048] (1) Preparation of Intermediate 4

[0049]

[0050] In a 100 mL round bottom flask, add 3′,5′-dihydroxyacetophenone (1.52 g, 10 mmol), 3,4-dihydro-2H-pyran (1.68 g, 20 mmol), pyridine p-toluenesulfonic acid ( PPTs, 0.13g, 0.5mmol), mixed, added dichloromethane (50mL), dissolved, magnetically stirred, stopped after 24h at 40°C. The reaction solution was taken, layered with 10% sodium hydroxide (50 mL) and dichloromethane (50 mL), and the lower organic layer was taken. The extracted liquid was washed twice with 30 mL of saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain compound 4 (3.12 g, yield 97.5%). 1 H NMR (500MHz, CDCl 3 )δ7.26(s, 2H), 6.93(s, 1H), 5.58(s, 2H), 3.81(q, 3H), 3.62(t, 2H), 2.55(s, 3H), 1.98-1.90(m ,4H), 1.60-1.52(m,4H), 1.52-1.48(m,4H).

[0051] (2) Preparation of Intermediate 7

[0052]

[0053] In a 100mL round bottom fl...

Embodiment 2

[0060] Embodiment 2: the preparation of compound b

[0061] (1) The preparation of intermediate 4 is the same as in Example 1

[0062] (2) Preparation of Intermediate 6

[0063]

[0064] In a 100mL round bottom flask, add p-hydroxybenzaldehyde (1.22g, 10mmol), 2-bromoethanol (1.25g, 10mmol), K 2 CO 3 (0.69g, 5mmol), mix, add DMF (50mL), dissolve, dissolve, magnetically stir, stop after 24h at 40°C. The reaction solution was taken, layered with 10% sodium hydroxide (50 mL) and dichloromethane (50 mL), and the lower organic layer was taken. The extracted liquid was washed twice with 30 mL of saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to obtain compound 6 (1.35 g, yield 81.3%). 1 H NMR (500MHz, CDCl 3 )δ9.86(s, 1H), 7.72(d, 2H, J=8.3Hz), 7.17(d, 2H, J=8.2Hz), 3.93(m, 3H), 3.82(m, 3H), 3.21( m, 1H).

[0065] (3) Preparation of intermediate 8 and final product b with reference to Example 1, the total yield o...

Embodiment 3

[0068] Embodiment 3: the preparation of compound c

[0069] The synthesis was carried out with reference to the preparation method of compound b in Example 2, bromoethane was used instead of 2-bromoethanol in the preparation of intermediate 6, and the total yield of compound c was 60.9%. The structural formula is as follows:

[0070]

[0071] ESI MS:297.7[M+H] +1 , 1 H NMR (500MHz, CDCl 3 )δ9.97(s,1H),9.52(s,1H),9.23(s,2H),7.66(d,2H,J=8.0Hz),6.83(m,3H),6.61(m,2H), 6.13 (s, 1H), 3.82 (m, 2H), 1.31 (m, 3H).

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Abstract

The invention discloses an arylpyrazole compound. The arylpyrazole compound has a structure shown in the description. The arylpyrazole compound has good selective PDE4 inhibition activity and weak PDE4D inhibition effect, and can show more excellent pharmacodynamic properties and small side effects compared with a traditional PDE4 inhibitor. The compound can be used for preparing medicines for treating arthritis, asthma, chronic obstructive pulmonary diseases, senile dementia, depression and the like.

Description

technical field [0001] The invention belongs to the field of chemistry and medicine, and in particular relates to an arylpyrazole compound and its application. The arylpyrazole compound has selective PDE4B inhibitory activity. Background technique [0002] Phosphodiesterases (Phosphodiesterases, PDEs) are the only super enzyme family that can hydrolyze cAMP and cGMP in the body. As the basic regulatory factors of the second messenger cyclic nucleotides, the PDEs family participates in the regulation of various physiological functions in the human body, such as cell growth, differentiation and migration, gene expression, mediator secretion, ion channel function, etc. Because of the complexity, diversity and tissue distribution of PDEs, they are gradually being regarded as new and important drug targets for the treatment of various diseases. PDEs inhibitors can achieve the purpose of treating diseases by inhibiting the activity of PDEs, regulating the concentration of cAMP an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/12A61P11/06A61P11/08A61P11/00A61P17/00A61P31/04A61P29/00A61P13/12A61P31/10A61P31/00A61P35/00A61P25/24A61P25/16A61P25/00A61P25/28A61P9/10A61P11/14A61P19/10A61P19/02A61P13/00
CPCA61P9/10A61P11/00A61P11/06A61P11/08A61P11/14A61P13/00A61P13/12A61P17/00A61P19/02A61P19/10A61P25/00A61P25/16A61P25/24A61P25/28A61P29/00A61P31/00A61P31/04A61P31/10A61P35/00C07D231/12
Inventor 余颖聪
Owner WENZHOU PEOPLES HOSPITAL
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