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Flavin derivatives

A compound and alkyl technology, applied in the field of flavin derivatives, can solve the problems of not identifying the type of nuclear switch, not identifying FMN, etc.

Inactive Publication Date: 2012-05-23
BIORELIX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Furthermore, no instances of FMN, TPP, nor any other nuclear switch type have been identified in humans so far

Method used

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preparation example Construction

[1036] The preparation method of the compound of the present invention:

[1037] The compounds of the invention can be prepared using methods described and exemplified herein and methods analogous thereto and methods well known in the chemical arts. These methods include, but are not limited to, those described below. In the description of the synthetic methods described herein, it is understood that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of experiment and work-up method, are chosen as standard conditions for this reaction, which are readily determined by recognized by those skilled in the art. Therefore, sometimes the reaction may need to be carried out at elevated temperatures or for longer or shorter periods of time. Those skilled in the art of organic synthesis understand that the functional groups present on different parts of the molecule must be compatible with the reagents and reactions propo...

Embodiment 1

[1059] In-line probing assays are described by Regulski and Breaker in "In-line probing analysis of riboswitches", (2008), Methods in Molecular Biology, Vol 419, pp 53-67, the content of which is incorporated by reference in its entirety. This in-line probing assay was used to evaluate the dissociation binding constants for each ligand described herein interacting with either the FMN riboswitch amplified from the B. subtilis genome or the CD3299 riboswitch amplified from C. difficile. By PCR and [5'- 32 P]-label generated templates were in vitro transcribed to prepare pre-mRNA leaders (Regulski and Breaker, In-line probing analysis of riboswitches (2008), Methods in Molecular Biology Vol 419, pp 53-67). Dissolve approximately 5 nM labeled RNA precursor in 20 mM MgCl at 25 °C 2 , 50 mM Tris HCl (pH 8.3, at 25°C) in the presence or absence of increasing concentrations of the respective ligands for 41 hours. Online cleavage products were separated by 10% polyacrylamide gel elec...

Embodiment 2

[1064] MIC determinations were performed in 96-well clear round bottom culture plates in a final volume of 100 μL according to the method established by the Clinical Laboratory Standards Institute (CLSI). Briefly, test compounds suspended in 100% DMSO (or another suitable solubilization buffer) are added to aliquots of media appropriate for the indicated pathogens to a total volume of 50 [mu]L. Serial 2-fold dilutions of this solution into successive tubes in the same medium yielded the test compound concentration range suitable for the assay. To each dilution of test compound in medium was added 50 [mu]l of bacterial suspension from overnight culture growth in medium appropriate for the indicated pathogen. The final bacterial inoculum was approximately 10 5 -10 6 CFU / well. After 18-24 hours of growth at 37°C, the MIC was defined as the lowest concentration of an antimicrobial detectable with the naked eye that completely inhibited the growth of the microorganism relative t...

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Abstract

The present invention relates novel flavin derivatives and other flavin derivatives, their use and compositions for use as riboswitch ligands and / or anti-infectives. The invention also provides method of making novel flavin derivatives.

Description

[0001] This application claims priority to Provisional Application No. 61 / 221,937, filed June 30, 2009, and Provisional Application No. 61 / 303,237, filed February 10, 2010, both of which are incorporated by reference in their entirety. technical field [0002] The present invention relates to flavin derivatives, uses thereof and compositions used as riboswitch ligands and / or anti-infectives. The invention also provides a preparation method of the neoflavin derivative. Background of the invention [0003] The rapid rate of increase in antibiotic resistance over the past few decades has raised serious concerns that currently available antibiotic treatment options will soon be ineffective. Due to the widespread use of antibiotics and the rapid rate of increase in bacterial resistance, in contrast to the decades-old availability of therapeutic chemical platforms, new drugs must be developed against bacterial pathogens. [0004] In many bacteria and fungi, RNA structures called ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D237/00
CPCC07D487/04A61P31/00A61P31/04A61K31/4985
Inventor P·D·G·克伊施P·威肯斯S·埃沃拉N·巴布拉斯A·拜罗J·伯曼H·考尔D·穆恩V·彭A·拉夫顿J·威尔森P·A·阿里斯托夫K·F·布鲁恩特B·R·狄克逊J·明D·奥斯特曼T·R·贝利奥蒂R·A·克鲁西尔B·R·伊万斯J·A·雷比H·J·朔斯塔莱兹D·昂德伍德M·纳维阿F·希尔沃利诺
Owner BIORELIX
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