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JAK (Janus kinase) and HDAC (histone deacetylase) double-target-spot inhibitor with 4-aminopyrazole structure, and preparation method and application thereof

An aminopyrazole and dual-target technology, which can be used in medical preparations containing active ingredients, anti-inflammatory agents, organic chemistry, etc., and can solve the problems that dual-target inhibitors have not been reported.

Active Publication Date: 2018-11-23
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, multi-target design strategies are widely used in the treatment of tumor diseases, but there are no reports of JAK and HDAC dual-target inhibitors with 4-aminopyrazole structure

Method used

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  • JAK (Janus kinase) and HDAC (histone deacetylase) double-target-spot inhibitor with 4-aminopyrazole structure, and preparation method and application thereof
  • JAK (Janus kinase) and HDAC (histone deacetylase) double-target-spot inhibitor with 4-aminopyrazole structure, and preparation method and application thereof
  • JAK (Janus kinase) and HDAC (histone deacetylase) double-target-spot inhibitor with 4-aminopyrazole structure, and preparation method and application thereof

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Experimental program
Comparison scheme
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Embodiment Construction

[0189] The terms and definitions used in this document have the following meanings:

[0190] "Alkane" refers to C1-C6 aliphatic chain, cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane.

[0191] "Aryl" refers to a group containing an aromatic carbocyclic ring and a substituted aryl group with substituents on the ring. The preferred aromatic ring contains 5-10 carbon atoms.

[0192] HEL cells are human leukemia cancer cells, K562 are human myeloid leukemia cells, MOLT4 cells are human lymphoma leukemia cells, and Jurkat cells are human acute T-cell leukemia cells. These cells are widely used in tumor research, biological experiments or cell culture, and have become Very important tool in medical research.

[0193] 3. Application of JAK and HDAC dual-target inhibitors containing 4-aminopyrazole structure

[0194] Application of a JAK and HDAC dual-target inhibitor compound containing a 4-aminopyrazole structure in the preparation of drugs for the prevention or...

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Abstract

The invention relates to a JAK (Janus kinase) and HDAC (histone deacetylase) double-target-spot inhibitor with a 4-aminopyrazole structure, a preparation method thereof and application of the compoundto preparation of drugs for preventing or treating blood-related diseases, solid tumors, inflammations and autoimmune diseases. The compound comprises structures shown as general formulas (I), (II),(III) and (IV). (The formulas are shown in the description.).

Description

technical field [0001] The invention relates to a JAK and HDAC dual-target inhibitor containing a 4-aminopyrazole structure, a preparation method and application thereof, and belongs to the technical field of organic compound synthesis and medical application. Background technique [0002] JAK kinase (including four subtypes of JAK1, JAK2, JAK3 and TYK2) is a tyrosine kinase that exists in the cytoplasm, and it is an important hub for many growth factors and cytokines to regulate signaling pathways. Induce signaling pathways mediated by cytokines and growth factors and activate STAT proteins to transduce signaling pathways into the nucleus to regulate gene expression. Mutations in JAK2 are often associated with the pathogenesis of diseases such as myeloproliferative neoplasms and leukemia (a type of hematologic malignancy), and JAK2 is frequently found in patients with myeloproliferative neoplasms V617F mutation. Myeloproliferative neoplasms include chronic myelogenous leu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D403/12C07D487/04A61K31/506A61K31/517A61K31/519A61P35/00A61P29/00A61P37/06A61P35/02A61P17/06A61P19/02
CPCC07D403/12C07D487/04
Inventor 张颖杰梁学武徐文方
Owner SHANDONG UNIV
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