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3,5-dinitrobenzamide compound containing isoindoline segment and preparation method thereof

A technology of benzamide and isoindoline, applied in the field of medicinal chemistry, can solve the problems of no in-depth research value, poor water solubility, unsatisfactory pharmacokinetic properties and the like

Inactive Publication Date: 2020-01-17
BEIJING TUBERCULOSIS & THORACIC TUMOR RES INST +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although some of the compounds showed good anti-tuberculosis activity in vitro, further studies found that the water solubility of these compounds was poor, which led to unsatisfactory pharmacokinetic properties, so there is no further research value

Method used

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  • 3,5-dinitrobenzamide compound containing isoindoline segment and preparation method thereof
  • 3,5-dinitrobenzamide compound containing isoindoline segment and preparation method thereof
  • 3,5-dinitrobenzamide compound containing isoindoline segment and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 13

[0062] Example 1 3,5 Dinitro-N-[(2-benzylisoindoline-5-yl)methyl]benzamide

[0063] Under argon protection, 3,5-dinitrobenzoic acid (100mg, 0.47mmol), bis(2-oxo-3-oxazolidinyl)phosphoryl chloride (BOP-Cl, 144mg, 0.56mmol) was dissolved in Anhydrous dichloromethane (DCM, 5mL), was added isoindol-5-ylmethylamine (84mg, 0.56mmol) and triethylamine (130mL, 0.94mmol) to the reaction solution, and stirred at temperature for 8h. After the reaction was completed, it was washed with water (10mLx3), and then the organic layer was washed with saturated sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was separated by column chromatography to obtain 84 mg of white solid (52% yield), mp: 103-105°C.

[0064] 1 H NMR (500MHz, CD 3 OD)δ9.14(s,1H),9.07(s,2H),7.46-7.39(m,5H),6.95-7.02(m,3H),4.65(s,2H),4.60(brs,4H), 3.65(s,2H).

[0065] MS-ESI(m / z):343.4(M+H) + .

[0066] HRMS-ESI:m / z Calcd...

Embodiment 2

[0067] Example 2 3,5-Dinitro-N-[(2-(2-fluorobenzyl)isoindoline-5-yl)methyl]benzamide

[0068] Same as the preparation method of the compound in Example 1, 3,5-dinitrobenzoic acid was reacted with 2-(2-fluorobenzyl)isoindol-5-yl)methylamine to obtain a light yellow solid (yield 42%), mp: 112-114°C.

[0069] 1 H NMR (500MHz, CDCl 3 )δ9.15(s,1H),8.95(s,2H),7.35(s,2H),7.18-7.15(m,3H),7.02(s,2H),6.76(brs,1H),4.55(d , J=5.28Hz, 2H), 4.91(brs, 4H), 3.88(s, 2H).

[0070] MS-ESI(m / z):451.4(M+H) + .

[0071] HRMS-ESI:m / z Calcd.for C 23 h 19 FN 4 o 5 (M+H) + : 451.41916; Found 451.41882.

Embodiment 3

[0072] Example 3 3,5-Dinitro-N-[(2-(3-fluorobenzyl)isoindoline-5-yl)methyl]benzamide

[0073] Same as the preparation method of the compound in Example 1, 3,5-dinitrobenzoic acid was reacted with 2-(3-fluorobenzyl)isoindol-5-yl)methylamine to obtain a light yellow solid (yield 58.1%), mp: 114-116°C.

[0074] 1 H NMR (500MHz, CDCl 3 )δ9.15(s,1H),8.97(s,2H),7.35(s,1H),7.18-7.15(m,5H),7.02(s,1H),6.76(brs,1H),4.58(d , J=5.28Hz, 2H), 4.92(brs, 4H), 3.88(s, 2H).

[0075] MS-ESI(m / z):451.4(M+H) + .

[0076] HRMS-ESI:m / z Calcd.for C 23 h 19 FN 4 o 5 (M+H) + : 451.41916; Found 451.41982.

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Abstract

The invention relates to a 3,5-dinitrobenzene formamide compound containing an isoindoline fragment, a preparation method and medical application thereof and anti-tuberculosis drug composition using the same as an effective ingredient, in particular to N-(isoindoline-5-methyl)-3,5-dinitrobenzene formamide compound. 2-potential N atoms in the isoindoline fragment of the compound are connected withan aromatic (heterocyclic) ring fragment or is connected with the aromatic (heterocyclic) ring fragment through methyne, n represents 0 and 1, and W represents the aromatic (heterocyclic) ring fragment in a formula (I).

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to 3,5-dinitrobenzamide compounds containing isoindoline fragments with anti-tuberculosis activity and a preparation method thereof, and an anti-tuberculosis drug composition containing them; more specifically Speaking, the present invention relates to a class of N-(isoindoline-5-ylmethyl)-3,5-dinitrobenzamide compounds, the 2-position N atom in its isoindoline segment directly Linked to the aromatic (hetero) ring segment or connected to the aromatic (hetero) ring segment through the methine group. Background technique [0002] Tuberculosis (TB) is one of the major infectious diseases caused by Mycobacterium tuberculosis (MTB), which seriously endangers human health. Since the 1980s, the incidence of drug-resistant TB, especially multi-drug-resistant TB (MDR-TB), has been increasing and the combination of TB and HIV / AIDS has caused the TB epidemic to rise again, becoming a major pu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/44C07D403/04C07D401/04C07D417/04C07D413/04A61K31/4439A61K31/506A61K31/422A61K31/427A61P31/06
CPCC07D209/44C07D401/04C07D403/04C07D413/04C07D417/04
Inventor 陆宇刘明亮吕凯黄国成汪阿鹏王洪建陶泽宇郭慧元
Owner BEIJING TUBERCULOSIS & THORACIC TUMOR RES INST