(3-(1H-1,2,3-triazole)phenyl)phosphoric acid derivative as well as preparation method and application thereof

Abstract

The invention relates to the technical field of medicinal chemistry, and discloses a (3-(1H-1,2,3-triazole)phenyl)phosphoric acid derivative derivative as shown in a formula X which is described in the specification. The derivative has good and broad-spectrum inhibitory activity on MBL and / or SBL enzyme, and can be used for preparing an MBL and / or SBL inhibitor. In addition, the compound provided by the invention can reverse the drug resistance of bacteria to carbapenem antibiotics. The (3-(1H-1,2,3-triazole)phenyl)phosphoric acid derivative disclosed by the invention has great potential in preparation of drugs for overcoming drug resistance of beta-lactam antibiotics (the carbapenem antibiotics).

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to (3-(1H-1,2,3-triazole)phenyl)phosphoric acid derivatives and a preparation method and application thereof. Background technique [0002] β-lactam antibiotics refer to a large class of antibiotics that contain a four-atom lactam ring in their chemical structure, including the most commonly used clinical penicillins, cephalosporins, carbapenems, and cephamycins, thiomycetes Atypical β-lactam antibiotics such as steroids and monocyclic β-lactams. β-lactam antibiotics are small-molecule antibacterial drugs widely used in clinical practice. They interfere with the synthesis of bacterial cell walls by inhibiting the activity of penicillin-binding proteins (PBPs), thereby leading to the death of bacteria. However, the efficacy of β-lactams is decreasing due to the rapid evolution and spread of bacterial resistance. The efficacy of carbapenem antibiotics, which are used as ...

AI Technical Summary

Problems solved by technology

However, the above-mentioned SBL inhibitors are ineffective against MBLs-regulated drug-resistant strains, so people continue to develop MBL inhibitors in order to obtain drugs against MBLs-producing drug-resistant strains

Although studies in recent years have found many compounds with good inhibitory activity on SBL or MBL, so far there is no MBL inhibitor on the market, and the existing inhibitors are not enough to solve the problem of bacterial resistance

In addition, because the structures and catalytic mechanisms of MBL and SBL are different, and carbapenem-resistant strains expressing both MBL and SBL have only emerged and spread in recent years, few compounds that jointly inhibit MBL and SBL have been reported so far.

Images