Application of 1,2,4 triazolo 4,3-B pyridazine derivative in preparation of anti-inflammatory factor storm drugs

A technology of pyridazine derivatives and inflammatory factors, applied in the field of medicine, can solve problems such as large side effects, limited drugs, high blood pressure and osteonecrosis

Active Publication Date: 2021-01-15
SUN YAT SEN UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the drugs currently available for anti-inflammatory cytokine storm are very limited, and non-specific combined treatment measures such as anti-infective drugs and glucocorticoids are often used.
Although glucocorticoids can non-specifically inhibit the storm of inflammatory factors, their use has relatively large side effects, and long-term use is likely to cause side effects such as superinfection, diabetes, osteoporosis, hypertension, and osteonecrosis
In recent years, monoclonal antibody drugs have also been used for anti-inflammatory factor storm (such as IL-6R receptor monoclonal antibody and GM-CSF monoclonal antibody). and the health care system have created a serious burden

Method used

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  • Application of 1,2,4 triazolo 4,3-B pyridazine derivative in preparation of anti-inflammatory factor storm drugs
  • Application of 1,2,4 triazolo 4,3-B pyridazine derivative in preparation of anti-inflammatory factor storm drugs
  • Application of 1,2,4 triazolo 4,3-B pyridazine derivative in preparation of anti-inflammatory factor storm drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1 C1632 inhibits the expression of various inflammatory factors

[0045] The inventor's team treated A549, Huh-7, THP1 and PBMC cells with C1632, and detected the effect of C1632 on the expression levels of inflammatory factors in HEK293T, A549, and Huh-7: cells were divided at 2 × 10 6 A 6-well plate was plated per well, 2 ml of DMEM complete medium was added to each well, and 240 μM C1632 was added for treatment for 48 h the next day, and the cells were lysed with Trizol to extract RNA for QRT-PCR analysis.

[0046] C1632 treatment of THP1 cells: THP1 cells by 5 × 10 5 Each well was seeded with 12-well plate, 1 ml of PRMI1640 complete medium per well, and PMA with a final concentration of 100 ng / μl was added to induce cell differentiation. The next day, the medium was changed to fresh medium and C1632 was added for 2 days of treatment. Add LPS or TNF-α with a final concentration of 100 ng / ml to stimulate for 8~12 h, collect the cell culture supernatant for L...

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Abstract

The invention discloses an application of a [1,2,4]triazolo[4,3-B]pyridazine derivative as shown in a formula (I) and a pharmaceutically acceptable salt or polymorphic substance thereof in preparationof anti-inflammatory factor storm drugs. According to the invention, the compounds can inhibit the expression and secretion of a variety of inflammatory factors by up-regulating let-7 expression, especially, expression and secretion of key factors IL-1RA, IL-1alpha, IL-1beta, IL-6, IL-10, IL-18, IL-22, IP-10, CCL2, GM-CSF, TNF-alpha and the like which form inflammatory factor storm, have good drug safety and strong inflammatory factor inhibition effect, and can be used as candidate drugs for resisting inflammatory factor storm.

Description

technical field [0001] The technical field of medicine of the present invention, more particularly, relates to the application of 1,2,4 triazolo 4,3-B pyridazine derivatives in the preparation of anti-inflammatory factor storm drugs. Background technique [0002] Inflammatory factors and cytokines are important humoral immune molecules, which can regulate various physiological functions of immune cells and organs to help the body resist foreign substances. Under normal circumstances, the expression of inflammatory factors and cytokines is strictly regulated by cells. However, factors such as viral infection or the side effects of certain drugs can cause disorder in the regulation mechanism of cellular inflammatory factors, resulting in excessive production of inflammatory factors and inflammatory factor storms. Inflammatory factor storm, also called "cytokine storm" or "hypercytokineemia", is a severe systemic inflammatory response. This reaction is manifested in the massiv...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D487/04A61K31/5025A61P29/00A61P37/00
CPCA61P29/00A61P37/00C07D487/04
Inventor 赵勇谢晨陈艳莲金和平
Owner SUN YAT SEN UNIV
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