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Benzoxazole derivative and preparation method and application thereof

A technology for benzoxazole derivatives, applied in the field of benzoxazole derivatives and their preparation, can solve the problems of poor solubility, difficult synthesis and purification, and low oral bioavailability, and achieve good anti-inflammatory activity and good The effect of inhibiting activity

Active Publication Date: 2019-04-05
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

[0050] The present invention also provides a preparation method of a benzoxazole derivative having a structure shown in formula (I), comprising:

[0051] The compound of formula (II) structure and the compound of formula (III) structure are reacted, obtain the compound of formula (I) structure;

[0052]

[0053] where the R 1 hydrogen, C1-C15 alkyl, halogen, C1-C15 alkoxy, nitro, cyano, C3-C8 cycloalkyl, C2-C12 heterocyclyl, -COR 2 、-COOR 2 、-SO 2 R 2 or -NR 3 R 4 ;

[0054] The R 2 , R 3 , R 4 Independently selected from hydrogen or C1~C10 alkyl;

[0055] Said n is 1, 2, 3 or 4;

[0056] said C3-C7 cycloalkyl, C2-C7 heterocyclyl, substituted C6-C20 aryl, unsubstituted C6-C20 aryl, unsubstituted C5-C20 heteroaryl or substituted C5-C20 C20 heteroaryl.

[0057] In the present invention, the present invention has no special requirements for the reaction method of the compound of the formula (II) structure and the compound of the formula (III) structure to obtain...

Embodiment 1

[0063]

[0064] Synthesis of 2-chloromethylbenzoxazole:

[0065] Add 2-aminophenol (1.635g), 1.2ml of chloroacetyl chloride, 0.5ml of pyridine, and 20ml of chlorobenzene into a 50ml round-bottomed flask, stir at room temperature for 2h, add 0.258g of p-toluenesulfonic acid, reflux for 6h, and monitor with TCL. After the reaction, chlorobenzene was evaporated, 100ml of water was added, extracted with ethyl acetate, 20ml*3, dried with anhydrous magnesium sulfate and then rotary evaporated. The product was passed through the column with DCM to obtain a yellow oily liquid as the product.

[0066] 1 H NMR (600MHz, CDCl 3 )δ7.73-7.70 (m, 1H), 7.53-7.51 (m, 1H), 7.38-7.32 (m, 2H), 4.73 (s, 2H)

Embodiment 2

[0068]

[0069] Synthesis of N-(Benzo[d]oxazol-2-ylmethyl)aniline

[0070]Put 2-chloromethylbenzoxazole, aniline, KI, K2CO3 into 10ml DMF at a molar ratio of 1:1:0.15:1, heat to reflux at 55°C, monitor the reaction by TLC, and the reaction is complete after about 6 hours. Extraction, drying, PE: DCM = 7: 1 column, a white solid was obtained with a yield of 82%.

[0071] 1 H NMR (600MHz, CDCl3) δ7.71-7.69 (m, 1H), 7.51-7.48 (m, 1H), 7.33-7.30 (m, 2H), 7.20 (dd, J=11.8, 4.1Hz, 2H), 6.79-6.74(m, 3H), 4.61(s, 2H).

[0072] 13 C NMR (151MHz, CDCl 3 )δ164.08, 150.85, 146.84, 140.86, 129.35, 129.25, 125.05, 124.43, 119.95, 118.61, 115.12, 113.21, 110.63, 77.21, 77.00, 76.79, 41.92.

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Abstract

The invention provides a benzoxazole derivative and a preparation method and application thereof. Studies discover that the benzoxazole derivative provided herein has good P2Y14 inhibitory activity and anti-inflammatory activity, and is suitable for the preparation of drugs to treat P2Y14 receptor-associated inflammatory diseases.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a benzoxazole derivative and a preparation method and use thereof. Background technique [0002] Cell signal transduction refers to the combination of extracellular factors with receptors (membrane receptors or nuclear receptors), and the obtained information is strengthened, differentiated, integrated and transmitted to downstream sensors, triggering a series of biochemical reactions in cells And the interaction between proteins, until the expression of genes required for cell physiological responses and the formation of various biological effects. G protein-coupled receptors are currently the largest family of membrane surface receptors, which are involved in various signal transmission processes. [0003] G protein-coupled receptors (GPCRs) are divided into three categories according to the type of G protein coupled downstream: G s protein, Gi protein, G q Protein and G ...

Claims

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Application Information

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IPC IPC(8): C07D263/56A61P29/00A61P19/02
CPCA61P19/02A61P29/00C07D263/56
Inventor 李环球胡庆华王维维庞京朱一凡
Owner SUZHOU UNIV