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Fluoroquinolone amido derivatives and application thereof

An alkyl and hydroxyl technology, applied in the field of fluoroquinolone amine derivatives, can solve the problems of increased risk of drug compatibility, poor patient compliance, and increased difficulty in dose control, shortening the treatment cycle and reducing the dosage , reducing the effect of the type of drug

Active Publication Date: 2020-05-01
SOUTHWEST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to the different compositions and targets, multi-targets can be divided into "multi-drug and multi-target" drugs (drug combination), "multi-drug single-target" drugs (multi-component drugs), "single-drug multi-target" drugs "Three types of drugs, the first two types of drug administration involve two or more drugs, due to the complexity of drug interactions, these two drug administration methods may have increased difficulty in dose control and increased risk of drug compatibility. Therefore, the design of single-drug multi-target compounds has gradually become a hot spot in the design of new drugs

Method used

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  • Fluoroquinolone amido derivatives and application thereof
  • Fluoroquinolone amido derivatives and application thereof
  • Fluoroquinolone amido derivatives and application thereof

Examples

Experimental program
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Effect test

preparation example 1-24

[0079] Add 1mmol Floxacin and 2mL DCM to a 100mL round bottom flask, cool in an ice bath, stir magnetically, add 3mmolNaHCO 3 After 20min, 2.5mmol chloroacyl chloride (Cl-(CH 2 ) n COCl, n=1, 2, 3) in DCM (2mL) solution (the drop rate is about 1d / 2s), the reaction continued under the ice bath (at 2-CC, moved to -5°C) after dropping, and TLC tracked and monitored to The reaction is over. Stirring was stopped and H was added 2 O 15mL and DCM 20mL, under stirring, use 1N HCl solution to adjust pH=3-4, if there is solid, then stand still, filter with suction, wash the filter cake 3 times with DCM, and keep the filter cake for further purification; the filtrate is transferred to a separatory funnel, The liquid was separated, the aqueous phase was extracted with DCM (15 mL×1), the organic phases were combined, washed with saturated NaCl solution (15 mL×1), the organic phase was collected, anhydrous NaCl 2 SO 4 dry. The crude product was spin-dried by a rotary evaporator, and t...

Embodiment 1-35

[0085] In the 100mL round bottom flask, add 1mmol of the intermediate of formula X, 5mL of toluene, 2mmol of Et 3 N, stir for 20-30min, add 2mmol isonicotinic acid (INA) or pyrazinecarboxylic acid (POA), after 10min, move to 110℃~120℃ oil bath for reflux reaction, monitor by TLC until the reaction is complete. Spin the reaction solution to dryness with a rotary evaporator, add 30mL DCM, stir to dissolve, filter with suction, wash the filter cake with DCM for 3 times, and wash the filtrate with 10% citric acid solution (15mL×1), collect the organic phase, anhydrous Na 2 SO 4 dry. The crude product was spin-dried by a rotary evaporator, the pure product was obtained by column chromatography, and the target product was obtained by vacuum drying.

[0086] Table 2 target compound formula XI synthetic result

[0087]

[0088]

[0089]

[0090] Table 3 target compound formula XI synthetic result

[0091]

[0092]

[0093]

[0094] Synthesis of formula XII serie...

Embodiment 36-41

[0097] Add 2mmol isoniazid, 4mmol NaHCO 3 and 5mL DCM, stirred at -5°C for 20min, then added dropwise 3mmol of chloroacetyl chloride solution (dropping rate is about 1d / 2s) with a constant pressure dropping funnel, and continued to react at -5°C, followed by TLC monitoring until the end of the reaction . While stirring, add DCM-CH 3 OH solution (V DCM : V CH3OH =2:1) ​​until the solids in the reaction flask no longer decrease, let stand, filter with suction, and use DCM-CH for the filter cake 3 OH solution was washed 3 times, and the filtrate was washed with anhydrous Na 2 SO 4 Dry and spin dry with a rotary evaporator to obtain a crude product, then add 5 mL of DCM and stir for 20 min, filter with suction, wash the filter cake 3 times with DCM, and dry in vacuo to obtain an intermediate for future use.

[0098] Add 1mmol of Floxacin and 4mmol of Et in a 100mL round bottom flask 3 N and 2mL DMF, after stirring for 20min, add the above-mentioned intermediate, and after 1...

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Abstract

The invention discloses fluoroquinolone amido derivatives and application thereof and belongs to the field of medicinal chemistry, and particularly relates to the fluoroquinolone derivative and application thereof. According to the invention, fluoroquinolone drugs are subjected to structural modification to obtain a compound shown as a formula I. The compound disclosed by the invention not only can be used for treating infection caused by mycobacterium tuberculosis and common bacteria, but also has inhibitory activity on persister bacteria, citrus pathogenic bacteria, nicotinamide N-methyltransferase (NNMT) and interleukin IL-17PPI. The preparation process of the compound is simple and convenient to operate and mild in condition, wherein numerous compounds with enhanced antibacterial activity, improved water solubility and reduced toxic and side effects are obtained, the dosage is expected to be reduced, the treatment period is shortened, the patient compliance is improved, and a new molecular type and research thought are provided for research of tuberculosis drugs and other diseases.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a fluoroquinolone amino derivative and its application. Background technique [0002] The present invention is a divisional application whose patent application number is 2017111028625. Tuberculosis (TB) is a chronic infectious disease mainly transmitted by respiratory tract caused by Mycobacterium tuberculosis (MTB). In addition to mainly causing tuberculosis, MTB can also affect all other organs of the human body. It is one of the major diseases that seriously endanger human health, and it is also a public health and social problem of global long-term common concern. Drug-resistant tuberculosis (DR-TB), especially multi-drug-resistant tuberculosis (DR-TB), is gradually increasing during the administration of anti-tuberculosis drugs, and curbing drug-resistant tuberculosis has become a very urgent research topic. [0003] The results and experience of global tube...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/14C07D401/04A61K31/4709A61K31/497A61P35/00A61P29/00A61P31/04A61P31/10A61P1/00A61P19/02A61P11/06A61P11/00A61P9/10A61P19/08A61P1/16A61P13/12A61P19/04A61P37/02
CPCC07D401/04C07D401/14A61P35/00A61P29/00A61P31/04A61P31/10A61P1/00A61P19/02A61P11/06A61P11/00A61P9/10A61P19/08A61P1/16A61P13/12A61P19/04A61P37/02Y02A50/30
Inventor 杨大成冯计周范莉黄敏谢建平胡军华牟希徐兴然郭思瑶付彬龙艳玲王帆张书虹
Owner SOUTHWEST UNIV
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