Flavonoid derivatives with rock kinase inhibitory effect

A compound, R27 technology, applied in the field of organic synthetic drugs, can solve the problems of destroying the protective effect of VEGF and the lack of effective drugs for diseases

Active Publication Date: 2021-09-21
SICHUAN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The existing drugs for diabetic retinopathy are mainly anti-VEGF antibodies, such as conbocept and ranibizumab, but these drugs are used in the late stage of the disease, that is, the stage of retinal angiogenesis, and there is no effective drug for the early stage of the disease, and Long-term application of anti-VEGF drugs may destroy the protective effect of VEGF on normal retinal tissue

Method used

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  • Flavonoid derivatives with rock kinase inhibitory effect
  • Flavonoid derivatives with rock kinase inhibitory effect
  • Flavonoid derivatives with rock kinase inhibitory effect

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0103] Embodiment 1 Preparation of compound 11 of the present invention

[0104]

[0105] Intermediate (2): Preparation of 7-Hydroxy-4-Hydrochromanone

[0106]

[0107] Put raw material (1) (2,4-dihydroxyacetophenone 1.0g, 6.57mmol) and triethyl orthoformate (6mL) in a round bottom flask at room temperature and stir, then add perchloric acid 600μL dropwise, and react for 1.5h , adding 50mL of ether, a large amount of red solid precipitated out. Suction filtration, the red solid was dissolved into a suspension with 30mL water and stirred at 80°C for 4 hours, extracted with ethyl acetate, water, and saturated sodium chloride after cooling, dried the organic phase with magnesium sulfate, suction filtration, and column chromatography white solid. The yield is 90%.

[0108] 1 H NMR (400MHz, DMSO) δ10.76(s, 1H), 8.14(d, J=6.0Hz, 1H), 7.87(d, J=8.7Hz, 1H), 6.91(dd, J=8.7, 2.2Hz , 1H), 6.84(d, J=2.2Hz, 1H), 6.21(d, J=6.0Hz, 1H).; MS (ESI, positive ion) m / z: 162.87[M+H] + ....

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Abstract

The invention relates to flavonoid derivatives with ROCK kinase inhibitory effect, and belongs to the technical field of organic synthetic medicines. The technical problem to be solved by the present invention is that the existing glaucoma treatment drugs are not effective, especially the lack of effective treatment drugs for glaucoma with normal intraocular pressure; the drugs for the treatment of diabetic retinopathy such as conbocept and ranibizumab can only be used In the late stage of the disease, it is ineffective for the early stage of the disease, and long-term use will destroy the protective effect of VEGF on normal retinal tissue. The technical solution to solve the above problems is to provide the compound shown in formula I. The experimental results show that the compound of the present invention has a significant inhibitory effect on ROCK kinase, can effectively reduce intraocular pressure, protect optic ganglion cells, reduce retinal reactive oxygen levels and inhibit retinal angiogenesis, and provide a new method for clinical treatment of glaucoma and diabetic retinopathy. choice of medication.

Description

technical field [0001] The invention relates to flavonoid derivatives with ROCK kinase inhibitory effect, and belongs to the technical field of organic synthetic medicines. Background technique [0002] ROCK kinases belong to serine / threonine protein kinases and are divided into ROCK I (ROCKβ) and ROCKII (ROCKα). ROCK kinase plays an important role in a series of cell life activities such as cell mitotic adhesion, cytoskeleton adjustment, muscle cell contraction, and tumor cell infiltration. Studies have shown that ROCK kinase is associated with a variety of diseases, including hypertension, pulmonary hypertension, cardiovascular disease, inflammation, autoimmune disease, lung disease and ophthalmic disease, etc. [0003] Existing treatments for glaucoma mainly focus on promoting aqueous humor outflow or reducing aqueous humor production to reduce intraocular pressure, such as prostaglandin derivative latanoprost that promotes aqueous humor outflow, or β-adrenergic receptor...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D311/22C07D311/36C07D413/12C07D405/12C07D417/12C07D215/227C07D317/64C07D319/18C07C237/40C07C255/57A61K31/352A61K31/422A61K31/427A61K31/4155A61K31/4704A61K31/277A61K31/167A61P27/02A61P27/06
CPCA61P27/02A61P27/06C07C237/40C07C255/57C07D215/227C07D311/22C07D311/36C07D317/64C07D319/18C07D405/12C07D413/12C07D417/12
Inventor 杨胜勇李琳丽
Owner SICHUAN UNIV
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