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Methods and compounds for the treatment or prevention of hypercytokinemia and severe influenza

A cytokine and blood technology, applied in organic chemistry, pharmaceutical formulations, medical preparations containing active ingredients, etc., can solve problems such as unsatisfactory

Pending Publication Date: 2020-11-03
POOLBEG PHARMA (UK) LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0037] As of the present invention, there remains an unmet need for a treatment that alleviates hypercytokineemia, particularly that associated with severe influenza virus infection

Method used

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  • Methods and compounds for the treatment or prevention of hypercytokinemia and severe influenza
  • Methods and compounds for the treatment or prevention of hypercytokinemia and severe influenza
  • Methods and compounds for the treatment or prevention of hypercytokinemia and severe influenza

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Embodiment Construction

[0109] p38 MAPK inhibitors are an established class of active agents (see eg Zarubin and Han, Cell Research (2005) 15, 11-18. doi:10.1038 / sj.cr.7290257). A wide range of p38 MAPK inhibitors are available to those skilled in the art (see, for example, Lee et al., Inhibition of p38 MAP kinase as a therapeutic strategy, Immunopharmacol., 2000; 47(2-3):185-201. doi:10.1016 / S0162 -3109(00)00206-X, which is hereby incorporated by reference). Examples of p38 MAPK inhibitors include VX-745, VX-702, RO-4402257, SCIO-469, BIRB-746, SD-0006, PH-787804, AMG-548, SB-681323 (domamod), LY2228820 , GW-856553, RWJ67657, and BCT-197 (Xing, L., MAP Kinase 2015, Vol. 4:5508, which is hereby incorporated by reference). These are examples of p38 MAPK inhibitors that have reached human trials

[0110]

[0111]

[0112]The preferred p38 MAPK inhibitor of the present invention is represented by formula I, or a pharmaceutically acceptable salt or solvate thereof:

[0113]

[0114] wherein R...

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Abstract

The invention provides a p38 MAPK inhibitor of Formula I, or a pharmaceutically acceptable salt or solvate thereof : Formula I for use in the treatment or prevention of hypercytokinemia in a human patient; wherein R is C1-3alkyl, optionally substituted by one or more halo, NR1R2 or hydroxy, and R1 and R2 are independently H, halo or C1-3alkyl, optionally substituted by one or more F. Also providedare compositions for use in the treatment or prevention of hypercytokinemia comprising the p38 MAPK inhibitor of Formula I; and methods for treating or preventing hypercytokinemia in a human patientin need thereof comprising administering to the patient a therapeutically or prophylactically effective amount of a p38 MAPK inhibitor of Formula I. The invention also provides a p38 MAPK inhibitor and an antimicrobial agent, such as an antiviral agent, for use in the treatment or prevention of hypercytokinemia.

Description

technical field [0001] The present invention relates to methods and compounds for the treatment or prevention of hypercytokineemia, particularly hypercytokineemia associated with severe influenza. The present invention also provides pharmaceutical compositions for treating and preventing hypercytokineemia and hypercytokineemia associated with severe influenza. Background technique [0002] Hypercytokineemia is defined as a sudden increase in circulating levels of proinflammatory cytokines such as IL-1, IL-6, and TNF (Croft, M., The role of TNF superfamily members in T-cell function and diseases, Nat Rev Immunol, 2009;9:271-85). [0003] Hypercytokineemia, or "cytokine storm," or "cytokine cascade," is associated with a variety of conditions, including infectious diseases, noninfectious diseases, autoimmune reactions, and adverse drug reactions. Inflammation is part of the complex biological response of body tissues to harmful stimuli such as viruses, damaged cells or irrit...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K31/395A61K31/437A61P31/16
CPCA61K45/06A61K31/395A61K31/437A61P31/16A61K2300/00C07D471/04A61K31/444A61K31/215
Inventor A·H·戴维斯P-M·霍伊V·桑德斯B·巴赫松S·瓦斯特N·E·托尔贝特P·A·惠特克
Owner POOLBEG PHARMA (UK) LTD
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