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Compound and preparation method and application thereof

A compound and drug technology, applied in the field of medicine, can solve problems such as drug resistance and side effects

Inactive Publication Date: 2014-07-30
SUZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to the toxic side effects of traditional drugs and the emergence of drug resistance, it is urgent to develop new anti-myeloma drugs

Method used

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  • Compound and preparation method and application thereof
  • Compound and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0125] The preparation of embodiment 1 compound C98

[0126] 1. Dissolve the compound of structure shown in formula VII (2g, 8.3mmol / L, 1.0eq), malonic acid (1.3g, 12.4mmol / L, 1.5eq) in 20ml of anhydrous pyridine, and drop into morpholine under stirring (72.28mg, 0.8mmol / L, 0.1eq), stirred under reflux at 80°C for 24h, after the reaction was completed, 2mol HCl was added to the reaction system, a large amount of solids precipitated, filtered, the filter cake was washed with water, a small amount of EA, and the filter cake was treated with an infrared lamp After drying, the obtained product 2 is a mixture, and the pale yellow solid is 2.4 g of the compound of formula VIII, which can be directly used in subsequent reactions.

[0127] Characterization of the structural compound shown in formula VIII: MS: [M-H]-: Found m / z280.8Calcd m / z281.0

[0128] 2. Suspend the compound of formula VIII (2.4g, 8.48mmol / L, 1.0eq) in the mixed solution of MeOH and DMSO, slowly add SOCl 2 And ad...

Embodiment 2

[0139] Example 2 Compound C98 inhibits the growth of multiple myeloma cells and leukemia cells

[0140] Culture a variety of multiple myeloma cells: H929, JJN3, KMS11, KMS18, LP1, MM.1S, OCI-MY5, OPM2, RPMI-8226, U266; leukemia cells: K562, Jurkat, AML-2, NB-4, THP-1.

[0141] Treated with different concentrations of C98, the concentrations of C98 were 0.39μmol / L, 0.78μmol / L, 1.56μmol / L, 3.125μmol / L, 6.25μmol / L, 12.5μmol / L, 25μmol / L. After 72 hours of treatment, cell viability was analyzed by MTS / PMS staining.

[0142] figure 2 The effects of different concentrations of C98 compounds on multiple myeloma cells are shown. The results show that C98 has an inhibitory effect on the growth and proliferation of multiple myeloma in a concentration-dependent manner.

[0143] image 3 The effect of different concentrations of C98 compounds on leukemia cells, the results show that C98 has an inhibitory effect on the proliferation and growth of leukemia cells in a concentration-depen...

Embodiment 3

[0145] Example 3 Compound C98 induces apoptosis of multiple myeloma cells

[0146] Culture LP1, OPM2, OCI-MY5, JJN3 cells.

[0147] Treated with different concentrations of C98, the concentration of C98 was 0 μmol / L, 2.5 μmol / L, 5 μmol / L, and the cells were collected after 24 hours of treatment, and Annexin V-FITC (labeled apoptotic cells) and PI (propidium iodide) were used to treat cells. ) double staining, and Annexin V was detected by flow cytometry + percentage of cells. The result is as Figure 4 and as shown in Table 1:

[0148] Table 1 Effects of different concentrations of C98 compounds on apoptosis of myeloma cells

[0149]

[0150] The results showed that: C98 can effectively induce the apoptosis of multiple myeloma cells, and with the increase of C98 drug concentration, the proportion of cells undergoing apoptosis also gradually increased. It shows that the apoptosis rate is concentration-dependent with C98.

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Abstract

The invention relates to the technical field of medicines, and particularly relates to a compound and a preparation method and application thereof. The compound has a structure shown as a formula I in the specification, is screened out by a computer simulation and molecular docking technology, and has the effects of inhibiting a PI3K (phosphatidyl inositol 3-kinase) path and inhibiting growth and activity of tumors, and the capability of inducing tumor cell apoptosis according to confirmations. Experiments show that the compound can apparently inhibit expression of key enzyme and phosphorylation in the PI3K signal path, the inhibition function has obvious time dependency and concentration dependency, and furthermore, experiments prove that the compound cannot inhibit the key enzyme in other metabolic pathways, but can inhibit the PI3K signal path specifically.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a compound and its preparation and application. Background technique [0002] Multiple myeloma (MM) is a malignant tumor derived from B cells. In recent years, the wide application of new chemotherapy drugs has made great progress in the treatment of multiple myeloma. However, the incidence of this cancer is increasing year by year and showing a trend of younger age. Cancer data report that myeloma is the second most common blood disease and is still considered an incurable disease. Due to the side effects of traditional drugs and the emergence of drug resistance, it is urgent to develop new anti-myeloma drugs. Among them, target-based drug design has become a hot spot for innovative drugs. [0003] Phosphatidylinositol-3-kinase (phosphoinositide 3-kinases, PI3K) signaling pathway controls many cell biological processes that are crucial in the development of tumors, including ...

Claims

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Application Information

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IPC IPC(8): C07D307/54C07D207/337C07D333/24A61K31/40A61K31/341A61K31/381A61P35/00
CPCC07D207/337C07D307/54C07D333/24
Inventor 毛新良侯廷军朱景宇乔春华
Owner SUZHOU UNIV
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