Indole nedd8 activating enzyme inhibitor, preparation method thereof and application in antitumor drugs

A technology of anti-tumor drugs and compounds, which is applied in the fields of anti-tumor drugs, drug combinations, organic chemistry, etc., and can solve the problem of no reports of anti-tumor drugs

Active Publication Date: 2021-08-20
BEIJING UNIV OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there are no reports of anti-tumor drugs targeting NEDD8 activating enzyme

Method used

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  • Indole nedd8 activating enzyme inhibitor, preparation method thereof and application in antitumor drugs
  • Indole nedd8 activating enzyme inhibitor, preparation method thereof and application in antitumor drugs
  • Indole nedd8 activating enzyme inhibitor, preparation method thereof and application in antitumor drugs

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Embodiment Construction

[0015] In order to better illustrate the present invention, examples are as follows:

[0016] The preparation of embodiment compound I-1

[0017] In 30ml of dichloromethane solvent, add 5mmol of 3,4,5-trimethoxyaniline, 5mmol of p-methoxybenzyl chloride and 10mmol of chloroacetyl chloride, add 10mmol of triethylamine, and stir at room temperature for 12 hours to prepare the compound 4. 1 mmol of compound 4 was dissolved in 10 ml of ethyl acetate, 1.2 mmol of 5-methoxyindole and 2 mmol of sodium hydroxide were added, stirred at room temperature for 5 hours, and compound I-1 was obtained by suction filtration.

[0018] The structure of compound I-1 is characterized as follows:

[0019] I-1: White solid, M.p.: 103~104℃; Yield: 50%. 1 H NMR (400MHz, DMSO-d 6 )δ7.17–7.09(m,4H),7.03(d,J=2.3Hz,1H),6.86(d,J=8.5Hz,2H),6.74(dt,J=11.9,6.0Hz,1H), 6.52(s,2H),6.30(d,J=3.0Hz,1H),4.80(d,J=13.3Hz,2H),4.76(s,2H),3.74(s,3H),3.71(d,J =8.6Hz,9H),3.65(s,3H). 13 C NMR (100MHz, DMSO-d 6 )δ178...

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Abstract

The invention discloses a compound containing an indole structure, a preparation method and the application of the NEDD8 activating enzyme as a target in antitumor drugs, and belongs to the field of medicinal chemistry. The indole derivative of the present invention has the following structure: the anticancer activity test in vitro shows that the compound I-1 has a certain inhibitory effect on various tumor cells. Enzyme inhibition experiments prove that indole derivative I‑1 selectively inhibits the activity of NEDD8 activating enzyme, which is valuable for studying the biological function of NEDD8 activating enzyme and developing NEDD8 activating enzyme inhibitor antitumor drugs.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a compound containing an indole structure, a preparation method thereof and an application as an NEDD8 activating enzyme inhibitor in antitumor drugs. Background technique [0002] NEDD8 activating enzyme is the rate-limiting enzyme in the process of protein ubiquitination Neddylation, inhibiting the activity of NEDD8 activating enzyme can reduce the activity of ubiquitin-proteasome system pathway and the degradation of related proteins, and induce tumor cell apoptosis. For the anti-tumor drugs that are still not on the market for this target, the anti-cancer small molecules MLN4924 and TAS4464 that have entered the clinical stage have severe side effects. It is of great clinical significance to find anti-tumor NEDD8 activating enzyme inhibitors with new structures. [0003] Indole is an aromatic heterocyclic compound, its chemical structure is composed of a benzene ring and a ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/08A61P35/00
CPCA61P35/00C07D209/08
Inventor 李军付冬君常安琪张云封
Owner BEIJING UNIV OF CHINESE MEDICINE
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