Amide bond containing heterocyclic compound, preparation method and application thereof

A technology for heterocyclic compounds and compounds, which is applied in the fields of amide bond-containing heterocyclic compounds and their preparation and application, and can solve the problems of poor curative effect of leukemia and the like

Inactive Publication Date: 2016-12-07
TIANJIN INT JOINT ACADEMY OF BIOTECH & MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] In order to solve the problem of poor curative effect of drugs used to treat leukemia in the prior art, according to one aspect of the present invention,

Method used

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  • Amide bond containing heterocyclic compound, preparation method and application thereof
  • Amide bond containing heterocyclic compound, preparation method and application thereof
  • Amide bond containing heterocyclic compound, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Example 1 Chemical Synthesis and Structure Identification of Heterocyclic Compounds Containing Amide Bonds with General Formula One

[0062] 1. General formula one structural formula is as follows:

[0063]

[0064] In the above general formula one, the substituent-R includes the following structures:

[0065]

[0066] 2. The chemical synthesis experimental procedure of the heterocyclic compound containing amide bond with general formula one (experimental procedure of the example compound contained in general formula one)

example 1

[0067] Example 1 Compound 7a: 4-((4-(2-aminoethyl)piperazin-1-yl)methyl)-N-(4-methyl-3-((4-(pyridine-3-yl) Synthesis and Structure Identification of Pyrimidin-2-yl)amino)phenyl)-3-(trifluoromethyl)benzamide

[0068]

[0069] 2.2.1.1: Compound 4: 4-bromomethyl-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amine}phenyl)-3-trifluoro Synthesis of methyl benzamide

[0070]

[0071] Compound 2 (621mg, 2.16mmol) was dissolved in 12mL of anhydrous dichloromethane, stirred at 0°C for 5 minutes, 553uL oxalyl chloride and 20uL DMF were added to the reaction solution in turn, the reaction solution was stirred at 0°C for 3 hours, and the reaction solvent was removed with a rotary evaporator , the residue was dissolved in 10 mL of anhydrous THF, 598 mg of potassium carbonate was added, compound 1 (500 mg, 1.8 mmol) was dissolved in 20 mL of THF and added dropwise to the reaction system, and stirred at room temperature for 6 hours. After the reaction was completed, 100 mL of water w...

example 2

[0081] Example 2 compound 7b: 4-((4-(2-isothiocyanate ethyl) piperazin-1-yl) methyl)-N-(4-methyl-3-((4-(pyridine- Synthesis and Structure Identification of 3-yl)pyrimidin-2-yl)amino)phenyl)-3-(trifluoromethyl)benzamide

[0082]

[0083] Under nitrogen protection, 8ml THF was added to a 25mL three-necked flask, stirred at 0°C for 5 minutes, compound 7a (270mg, 0.457mmol), carbon disulfide (348mg, 4.57mmol) and DCC (N,N'-dicyclohexylcarbonyl Amine, 94.3mg, 0.457mmol), react at 0°C for 2 hours. After the reaction, the solvent was removed by spin, and the residue was purified by column chromatography to obtain 191.5 mg of white solid, yield: 66.2%.

[0084] HRMS-ESI(+): C 32 h 31 f 3 N 8 The calculated value of OSH is 633.2549, and the measured value is 633.2485;

[0085] 1 H NMR (400MHz, CDCl 3 ): δppm 9.23(d, J=1.6Hz, 1H), 8.67(dd, J=1.2, 4.8Hz, 1H), 8.59(s, 1H), 8.49(d, J=5.2Hz, 1H), 8.46( d,J=8.0Hz,1H),8.16(s,1H),8.12(s,1H),8.01(d,J=8.0Hz,1H),7.92(d,J=7.6Hz,1H),7.3...

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Abstract

The invention provides an amide bond containing heterocyclic compound, a preparation method and application thereof. Specifically, the amide bond containing heterocyclic compound has a structural general formula shown as the specification. Cellular level experiments find that the amide bond containing heterocyclic compound provided by the invention can inhibit proliferation of K562-3d, HL60, and KG1a cells, especially the example 1-5 compounds (compounds 7a to 7e) also can realize the effect of inhibiting the proliferation of K562-3d, HL60, and KG1a cells under a drug concentration lower than that of the positive control drug imatinib. Therefore, the amide bond containing heterocyclic compound provided by the invention can be used for treating leukemia.

Description

technical field [0001] The invention relates to a heterocyclic compound containing an amide bond, a preparation method and application thereof. Background technique [0002] Leukemia, also known as blood cancer, is a kind of clonal malignant disease with abnormal hematopoietic stem cells. The leukemia cells in its clones lose the ability to further differentiate and mature and stagnate at different stages of cell development. In the bone marrow and other hematopoietic tissues, a large number of leukemia cells proliferate and accumulate and infiltrate other organs and tissues, and at the same time inhibit normal hematopoiesis. The clinical manifestations are anemia, bleeding, infection and infiltration of various organs. [0003] Leukemia is usually divided into: 1) acute leukemia; 2) chronic leukemia; 3) special types of leukemia. [0004] Acute leukemia is a clonal malignant disease with abnormal hematopoietic stem cells. The leukemia cells in its clones lose the ability...

Claims

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Application Information

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IPC IPC(8): C07D401/04A61K31/506A61P35/02
Inventor 饶子和杨诚陈悦白翠改郭宇李永涛王静晗孟凡非潘成文
Owner TIANJIN INT JOINT ACADEMY OF BIOTECH & MEDICINE
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