A kind of medicine for preventing and treating acute kidney injury and its preparation method and application

A pharmaceutical and compound technology, applied in the field of oxazolopyrimidine compounds, can solve the problems of cell surface S1P1 reduction, lymphocyte reduction, etc., and achieve therapeutically applicable effects

Active Publication Date: 2018-12-04
MUDANJIANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it is believed that S1P 1 Functional antagonists or antagonists act by inhibiting the return of internalized S1P1 receptors to the cell surface or inhibiting S1P 1 Activation leads to lymphopenia, which leads to cell surface S1P 1 Significant and sustained reduction in

Method used

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  • A kind of medicine for preventing and treating acute kidney injury and its preparation method and application
  • A kind of medicine for preventing and treating acute kidney injury and its preparation method and application
  • A kind of medicine for preventing and treating acute kidney injury and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1: 7-(1H-indole-7-carbonyl)oxazol[5,4-d]pyrimidin-2-yl 5-guanidinopyrimidine-2-carboxylate (Compound 1)

[0043]

[0044] In a three-necked flask equipped with a nitrogen protection device, a thermometer, and a reflux condenser, add 2.7g (0.015mol) of 5-guanidinopyrimidine-2-carboxylic acid and toluene (100ml) under nitrogen protection, and stir to make it dissolve. Then add 2.6g (0.016mol) of carbonyldiimidazole, heat to 80°C, and react for 2 hours, then add dropwise 2.2g (0.016mol) of oxazol[5,4-d]pyrimidin-2-ol in toluene (50ml) solution, and then heated to reflux, and reacted for 4 hours. After cooling the reaction solution, the solvent was evaporated under reduced pressure. The residue was washed with water and recrystallized with ethanol to obtain a white solid oxazol[5,4-d]pyrimidine-2- 3.9 g of 5-guanidinopyrimidine-2-carboxylate, yield 87%, ESI-MS: 301.07 [M+H] + .

[0045] Add aluminum trichloride (5.6g, 44.0mmol), toluene (100ml) into a three-nec...

Embodiment 2

[0049] Example 2: 7-(piperidine-4-carbonyl)oxazol[5,4-d]pyrimidin-2-yl 5-guanidinopyridine-2-carboxylate (Compound 2)

[0050]

[0051] According to the method of Example 1, replace 5-guanidinopyrimidine-2-carboxylic acid with 5-guanidinopyridine-2-carboxylic acid, and replace 1H-indole-7-acyl chloride with piperidine-4-acyl chloride to obtain a white solid , total yield 51%, ESI-MS: 411.15[M+H] + .

Embodiment 3

[0052] Example 3: 5-fluoro-7-(1H-pyrazole-5-carbonyl)oxazol[5,4-d]pyrimidin-2-yl 5-guanidinopyrimidine-2-carboxylate (Compound 3)

[0053]

[0054] According to the method of Example 1, replace oxazol[5,4-d]pyrimidin-2-ol with 5-fluoro-oxazol[5,4-d]pyrimidin-2-ol, and use 1H-pyrazole-5- Acid chloride replaced 1H-indole-7-acyl chloride to give a bright white solid with a total yield of 45%, ESI-MS: 413.08[M+H] + .

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Abstract

The invention relates to oxazole-pyrimidine compound for preventing and treating acute kidney injury, a preparation method thereof, and a pharmaceutical composition containing same. The oxazole-pyrimidine compound has S1P1 agonist activity and can be applied with acute kidney injury protection dose and cannot lead to lymphopenia; in case of being applied with high dose, the oxazole-pyrimidine compound leads to limited lymphopenia; in addition, the oxazole-pyrimidine compound is applicable to the treatment of acute kidney injury.

Description

technical field [0001] The invention relates to an oxazolopyrimidine compound for preventing or treating acute kidney injury, a preparation method thereof, and a pharmaceutical composition containing the same. Background technique [0002] Acute kidney injury (AKI) is a group of clinical syndromes, which refers to sudden (within 1-7d) and sustained (>24h) sudden decline in renal function, defined as an increase in serum creatinine (SCr) of at least 0.5 mg / dl, manifested as It is azotemia, water-electrolyte and acid-base balance, and systemic symptoms of the whole body, which may be accompanied by oliguria (<400ml / 24h or 17ml / h) or anuria (<100ml / 24h). [0003] The most common causes of AKI are sepsis, major surgery, hypovolemia, and drugs. Risk factors for AKI include older age (>75 years), chronic kidney disease, atherosclerotic peripheral vascular disease, heart failure, liver disease, diabetes, and nephrotoxic drugs. However, there is currently no widely acc...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D498/04A61K31/519A61P13/12
CPCC07D498/04
Inventor 李海红赵婉馨郭永波刘立平王佳莹黄新欣
Owner MUDANJIANG MEDICAL UNIV
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