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Application of pyrrolidin-2-one compounds in the preparation of drugs related to multiple myeloma

A multiple myeloma, compound technology, applied in the field of medicinal chemistry and pharmacotherapeutics, can solve the problems of undruggability, key interaction site lag, etc., and achieve good c-Myc inhibitory effect

Active Publication Date: 2021-12-24
XUZHOU MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the disorder of c-Myc homodimers and heterodimers, and the hysteresis of key interaction sites, existing c-Myc inhibitors cannot be drugged

Method used

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  • Application of pyrrolidin-2-one compounds in the preparation of drugs related to multiple myeloma
  • Application of pyrrolidin-2-one compounds in the preparation of drugs related to multiple myeloma
  • Application of pyrrolidin-2-one compounds in the preparation of drugs related to multiple myeloma

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Experimental program
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Embodiment 1

[0080] Experimental methods and results

[0081] 1. Cell Viability Experiment

[0082] Experimental principle: The reagent contains WST-8, which is reduced by the dehydrogenase in the cell under the action of the electron carrier 1-methoxy-5-methylphenazinium dimethyl sulfate (1-Methoxy PMS) Highly water-soluble yellow formazan product (Formazan dye). The amount of formazan produced is directly proportional to the number of living cells. This feature can therefore be used directly for cell proliferation and toxicity assays.

[0083] Experimental steps:

[0084] 1. Plating: Two kinds of humanized myeloma cells in the logarithmic growth phase, RPMI-8226 and U266, were inoculated in a 96-well plate, with 100 μL of cell suspension per well, and the number of cells was 5×10 3 For the blank control group, only 100 μL of complete medium RPMI-1640 containing 10% FBS was added, and 3 to 5 duplicate wells were set for each group.

[0085] 2. RPMI-8226 and U266 treated with differen...

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Abstract

The invention relates to the application of a class of pyrrolidin-2-ketone compounds in the preparation of drugs related to multiple myeloma, which belongs to the field of medicinal chemistry and pharmacotherapy. The compounds have obvious enzyme inhibitory effect on c-Myc protein. The compound represented by formula I provided by the present invention, isomers or pharmaceutically acceptable salts thereof can be used in the preparation of drugs related to multiple myeloma.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry and pharmacotherapeutics, and specifically relates to the application of pyrrolidin-2-one compounds in the preparation of drugs related to multiple myeloma, especially the application of drugs related to c-Myc inhibitors. Background technique [0002] Multiple myeloma (multiple myeloma, MM) is a common plasma cell malignancy in the hematological system, mostly in middle-aged and elderly people, accounting for about 13% of hematological tumors. In recent years, with the continuous maturity of hematopoietic stem cell transplantation technology and the advent of first-line therapeutic drugs such as immunomodulators and proteasome inhibitors, the survival period of patients with multiple myeloma has been continuously prolonged, but it is still not completely cured. Tumor drug resistance is an important issue limiting the treatment outcome of this disease. Therefore, it is of great clinica...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/4184A61P35/00C07D403/04
CPCA61K31/4184A61P35/00C07D403/04
Inventor 高剑姚若斯
Owner XUZHOU MEDICAL UNIV
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