1606-75-3Relevant articles and documents
Phosphonodifluoropyruvate is a mechanism-based inhibitor of phosphonopyruvate decarboxylase from Bacteroides fragilis
Pallitsch, Katharina,Rogers, Megan P.,Andrews, Forest H.,Hammerschmidt, Friedrich,McLeish, Michael J.
, p. 4368 - 4374 (2017)
Bacteroides fragilis, a human pathogen, helps in the formation of intra-abdominal abscesses and is involved in 90% of anaerobic peritoneal infections. Phosphonopyruvate decarboxylase (PnPDC), a thiamin diphosphate (ThDP)-dependent enzyme, plays a key role in the formation of 2-aminoethylphosphonate, a component of the cell wall of B. fragilis. As such PnPDC is a possible target for therapeutic intervention in this, and other phosphonate producing organisms. However, the enzyme is of more general interest as it appears to be an evolutionary forerunner to the decarboxylase family of ThDP-dependent enzymes. To date, PnPDC has proved difficult to crystallize and no X-ray structures are available. In the past we have shown that ThDP-dependent enzymes will often crystallize if the cofactor has been irreversibly inactivated. To explore this possibility, and the utility of inhibitors of phosphonate biosynthesis as potential antibiotics, we synthesized phosphonodifluoropyruvate (PnDFP) as a prospective mechanism-based inhibitor of PnPDC. Here we provide evidence that PnDFP indeed inactivates the enzyme, that the inactivation is irreversible, and is accompanied by release of fluoride ion, i.e., PnDFP bears all the hallmarks of a mechanism-based inhibitor. Unfortunately, the enzyme remains refractive to crystallization.
Synthesis of phosphonated carbocyclic 2′-oxa-3′-aza- nucleosides: Novel inhibitors of reverse transcriptase
Chiacchio, Ugo,Balestrieri, Emanuela,Macchi, Beatrice,Iannazzo, Daniela,Piperno, Anna,Rescifina, Antonio,Romeo, Roberto,Saglimbeni, Monica,Sciortino, M. Teresa,Valveri, Vincenza,Mastino, Antonio,Romeo, Giovanni
, p. 1389 - 1394 (2005)
Phosphonated carbocyclic 2′-oxa-3′-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of the obtained compounds have been investigated. Phosphonated carbocyclic 2′-oxa- 3′-aza-nucleosides, while showing low levels of cytotoxicity, exert a specific inhibitor activity on two different reverse transcriptases, which is comparable with that of AZT, opening new perspectives on their possible use as therapeutic agents, in anti-retroviral and anti-HBV chemotherapy.
Preparation method of diethyl (formylmethyl) phosphonate
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Paragraph 0053; 0060-0064; 0071-0075; 00582-0085, (2019/07/04)
The invention discloses a preparation method of diethyl (formylmethyl) phosphonate, which comprises the following steps: under the protection of inert gas, tetraethyl methylene disphosphonate is mixedwith a reaction solvent, carbanion is generated under the action of a base, and HWE condensation reaction is carried out with ethyl formate to obtain 2-ethoxy vinyl phosphonate diethyl ester; hydrolysis reaction: diethyl (formylmethyl) phosphonate is synthesized by hydrolysis of 2-ethoxy vinyl phosphonate diethyl ester under acidic conditions in the airtight condition. The preparation method of the invention is simple and easy to obtain reaction raw materials, and can be used for obtaining diethyl (formylmethyl) phosphonate by an industrialized method.
Process for Preparing Cinacalcet and Pharmaceutically Acceptable Salts Thereof
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Paragraph 0093, (2015/10/05)
The present patent application relates to a process for preparing, cinacalcet or a pharmaceutically acceptable salt thereof, which comprises reacting 3-trifluoromethylbenzaldehyde having the following formula (II) with the phosphorus-comprising derivative having the following formula all) in which R1 and R2, which may he identical or different, are each a (C1-C6)alkyl group. The present invention also relates to the phosphorus-comprising derivative having the formula (III), to the use thereof and to the process for preparing same. The present invention also relates to the phosphate salt of cinacalcet and to uses thereof.
