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Benzoxazole derivative, and preparation method and application thereof

A technology for benzoxazole and derivatives, applied in the field of benzoxazole derivatives and their preparation, can solve the problems of poor solubility, difficult synthesis and purification, low oral bioavailability, etc., and achieves good inhibitory activity and good resistance. Inflammatory activity, good activity effect

Active Publication Date: 2020-03-17
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, 2-naphthoic acids have the highest activity and selectivity. However, the reported inhibitors of 2-naphthoic acids have defects such as poor solubility, low oral bioavailability, and difficulty in synthesis and purification. Further discussion on the structure-activity relationship is required. and biological evaluation have brought great difficulties
Therefore, searching for P2Y14 receptor antagonists with new structure types and improving the poor druggability of 2-naphthoic acid inhibitors has become an important choice for discovering strong activity. A new strategy for P2Y14 receptor inhibitors

Method used

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  • Benzoxazole derivative, and preparation method and application thereof
  • Benzoxazole derivative, and preparation method and application thereof
  • Benzoxazole derivative, and preparation method and application thereof

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preparation example Construction

[0017] The present invention also provides a preparation method of a benzoxazole derivative having a structure shown in formula (I), comprising:

[0018] The compound of formula (II) structure and the compound of formula (III) structure are reacted, obtain the compound of formula (I) structure;

[0019]

[0020] Wherein, the R is hydrogen, C1-C10 alkyl or halogen;

[0021] said It is a substituted or unsubstituted C4-C10 heterocycloalkyl group, a substituted or unsubstituted C4-C10 heterocyclic aryl group, or a substituted or unsubstituted C6-C20 aryl group.

[0022] According to the present invention, the present invention will react the compound of formula (II) structure and the compound of formula (III) structure, obtain the compound of formula (I) structure; Wherein, the present invention does not have special requirement to the method condition of reaction, the skilled artisan A skilled person can select a suitable preparation process according to the reaction raw m...

Embodiment 0

[0030]

[0031] Synthesis of 3-(benzo[d]oxazol-2-yl)aniline:

[0032] Add o-aminophenol (1g), m-aminobenzoic acid (1.256g), and 10mL polyphosphoric acid (PPA) into a 50mL round-bottomed flask, heat at 185°C, and reflux for 6h. After the reaction, cool to room temperature and use a cold Neutralize with 6N NaOH, filter the precipitate, and dry it. Dissolve the precipitate with ethyl acetate, filter several times, collect the filtrate, and spin dry. The product was passed through the column with petroleum ether:ethyl acetate (PE:EA) = 4:1, and the red solid was obtained as the product.

[0033] 1H NMR (600MHz, cdcl3) δ7.76-7.74 (m, 1H), 7.63 (d, J = 7.7Hz, 1H), 7.58-7.54 (m, 2H), 7.34-7.31 (m, 2H), 7.28 ( t, J=7.8Hz, 1H), 6.82(dd, J=8.0, 2.1Hz, 1H).

Embodiment 1

[0035]

[0036] Synthesis of N-(3-(benzo[d]oxazol-2-yl)phenyl)-2-(4-chlorophenyl)acetamide:

[0037] 3-(Benzo[d]oxazol-2-yl)aniline, 4-chlorophenylacetic acid, EDCI, HOBt, DIPEA were added to 10 mL of DMF in a molar ratio of 1:1:1.5:1.5:3, The reaction was monitored by TLC. After the reaction was completed, it was quenched by adding water, extracted, dried, and spin-dried. Add a small amount of ethyl acetate to precipitate the product, filter and dry.

[0038] 1 H NMR (600MHz, DMSO) δ8.58(s, 1H), 7.86(d, J=7.6Hz, 1H), 7.79-7.72(m, 3H), 7.52(t, J=7.9Hz, 1H), 7.43 -7.34(m, 6H), 3.68(s, 2H).

[0039] 13 C NMR(151MHz,DMSO)δ169.20,162.12,150.20,141.44,139.91,134.73,131.37,131.09,129.90,128.27,126.85,125.62,124.94,122.25,122.06,119.86,117.63,110.94,42.48,39.94,39.80 , 39.66, 39.52, 39.38, 39.24, 39.10.

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Abstract

The invention provides a benzoxazole derivative, and a preparation method and an application thereof. The benzoxazole derivative provided by the invention, as a P2Y14 inhibitor, has relatively good inhibitory activity and anti-inflammatory activity; furthermore, research finds that the benzoxazole derivative also has good activity on P2Y14 receptor related hyperuricemia and acute gouty arthritis,and can be used as a medicine for treating hyperuricemia and acute gouty arthritis.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a benzoxazole derivative and a preparation method and application thereof. Background technique [0002] P 2 Y 14 The receptor belongs to the delta-branch of rhodopsin-like G protein-coupled receptors (GPCRs). It inhibits 3′,5′-cyclic adenosine monophosphate (cAMP) production through the Gi protein and is activated by uridine-5′-diphosphoglucose (UDPG) and other endogenous UDP-sugars. P 2 Y 14 Receptors mainly exist in the heart, placenta, adipose tissue, gastrointestinal tract and peripheral immune cells, and participate in pro-inflammatory and pyroptotic processes. Their activation enhances neutrophil chemotaxis and promotes the release of mediators from mast cells. Recent studies have shown that in P 2 Y 14 In receptor knockout mice, P 2 Y 14 Antagonism of the receptor has potential therapeutic effect on diabetes. It has also been reported that UDP and UDPG act as ...

Claims

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Application Information

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IPC IPC(8): C07D263/57C07D413/12A61P19/06A61P19/02
CPCC07D263/57C07D413/12A61P19/06A61P19/02
Inventor 李环球王维维胡庆华宋佳滔
Owner SUZHOU UNIV
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