Compound with multi-target inhibition effect, composition, functional molecule and application of compound

A compound and ring atom technology, applied in the field of multi-target inhibitory compounds, can solve problems such as poor therapeutic effect

Active Publication Date: 2021-07-16
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of the reported dual-target inhibitors of BET and kinases were found accidentally, or were furth

Method used

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  • Compound with multi-target inhibition effect, composition, functional molecule and application of compound
  • Compound with multi-target inhibition effect, composition, functional molecule and application of compound
  • Compound with multi-target inhibition effect, composition, functional molecule and application of compound

Examples

Experimental program
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Example Embodiment

[0133] The present invention also provides the preparation method of the above compound, including the following steps:

[0134] S101: Provides structural compounds shown in formula (I-1);

[0135]

[0136] Where P represents a halogen;

[0137] Among them, the definition of each group in the structural compound shown in Formula (I-1) is as described above, and will no longer be described later.

[0138] S102: Provides a structural compound shown in formula (I-2);

[0139]

[0140] The definition of each group in the structural compound shown in Formula (I-2) is as described above, and will not be described herein.

[0141] Further, step S102 includes the following steps:

[0142] S1021: Cry compound A and amino acid NH 2 R 1 CHCOOH reacts to obtain compound B;

[0143] S1022: Compound C is obtained by reducing the compound B.

[0144] S1023: Aminate the compound C and the corresponding ketone reducing the compound D;

[0145] S1024: Reacting compound D with a haloalkyl group ...

Example Embodiment

[0194] Example 1

[0195]

[0196] (a) Compound 1A (25 g, 113.64 mmol), D-alanine (11.12 g, 125.0 mmol), potassium carbonate (17.25 g, 125.0 mmol) is dissolved in 500 ml of ethanol: water = 3: 1 mixed solvent, 80 The heating was refluxed for 8 hours, and the reaction was monitored with a TLC plate. After the reaction was completed, the solvent was cooled to room temperature, evaporated in water, dissolved in water, and adjusted pH to 1-2 with 1N HCl, with a large amount of yellow solid precipitation, filtered, washed with 200 mL The solid, the yellow solid was dried in a vacuum drying tank, i.e., Compound 1b, yield 88%.

[0197] 1 H NMR (400MHz, CDCL 3 Δ8.35 (D, J = 6.9 Hz, 1H), 8.06 (D, J = 9.1 Hz, 1H), 6.90 (S, 1H), 6.85 (D, J = 9.2 Hz, 1H), 4.33 (P, J = 7.0Hz, 1H), 1.67 (D, J = 7.0 Hz, 3H).

[0198] (b) Compound 1b (28.7 g, 99.31 mmol), potassium carbonate (27.41 g, 198.62 mmol) was dissolved in 500 ml of water, and the sodium sulfate (86.45 g, 496.55 mmol) was slowly added, ...

Example Embodiment

[0216] Example 2

[0217]

[0218] Example 2 is prepared from the same method in Example 1, in addition to pyridin-3-boric acid in step (j) in Example 1, the compound of Example 2 was prepared using the same method as in Example 1.

[0219] 1 H NMR (400MHz, DMSO-D 6 Δ9.67 (S, 1H), 9.35 (D, J = 2.2 Hz, 1H), 8.74 (DD, J = 4.8, 1.6 Hz, 1H), 8.59 (D, J = 5.2 Hz, 1H), 8.49 ( DT, J = 8.0, 2.0 Hz, 1H), 7.63-7.54 (M, 2H), 7.47 (D, J = 5.1 Hz, 1H), 7.30 (DD, J = 8.7, 2.1 Hz, 1H), 7.03 (D , J = 8.7Hz, 1H), 4.11 (Q, J = 6.7 Hz, 1H), 3.89 (p, j = 6.6 Hz, 1H), 3.26 (S, 3H), 1.28 (D, J = 6.6Hz, 3H ), 1.21 (d, j = 6.5 Hz, 3H), 0.99 (D, J = 6.7 Hz, 3H) .LC-MS (ESI) [M + H] + : 388.22.

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Abstract

The invention relates to a compound with a multi-target inhibition effect, a composition, a functional molecule and application of the compound. The compound has a structure shown in a formula (I), wherein K in the formula is as shown in the specification. The compound has an inhibition effect on BET and kinase double targets and can simultaneously act on different signal channels of tumor cell growth to achieve a better treatment effect.

Description

[0001] This application claims the priority of the Chinese patent application submitted to the China Patent Office on January 15, 2020, with the application number 2020100400404, and the title of the invention is "multi-target inhibitory compound, composition, functional molecule and its application", all of which The contents are incorporated by reference in this application. technical field [0002] The invention relates to the technical field of medicinal chemistry, in particular to multi-target inhibitory compounds, compositions, functional molecules and applications thereof. Background technique [0003] Complex diseases can often be attributed to the dysregulation of multiple signaling pathways and physiological processes, which are difficult to be cured by the specific modulation of a single target. Multidrug inhibition, as an effective strategy, has received extensive attention in current anticancer drug development. Compared with single-target or combination therap...

Claims

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Application Information

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IPC IPC(8): C07D471/04C07D403/12C07D487/04C07D403/14C07D401/12C07D401/14C07D413/12C07D413/14A61K31/506A61K31/498A61P35/00A61P43/00
CPCC07D471/04C07D403/12C07D487/04C07D403/14C07D401/12C07D401/14C07D413/12C07D413/14A61P35/00A61P43/00A61K31/498A61K31/506A61K31/497A61K31/422A61P35/04
Inventor 熊兵沈竞康缪泽鸿陈丹琦吕铠铠曹丹燕李艳莲王昕陈驎
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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