Jin, Wen Bin; Xu, Chen; Cheung, Qipeng; Gao, Wei; Zeng, Ping; Liu, Jun; Chan, Edward W. C.; Leung, Yun-Chung; Chan, Tak Hang; Wong, Kwok-Yin; Chen, Sheng; Chan, Kin-Fai published the artcile< Bioisosteric investigation of ebselen: Synthesis and in vitro characterization of 1,2-benzisothiazol-3(2H)-one derivatives as potent New Delhi metallo-β-lactamase inhibitors>, Synthetic Route of 21725-69-9, the main research area is benzoisothiazolone preparation metallo beta lactamase inhibitor SAR; 1,2-benzisothiazol-3(2H)-one; Bioisosteric replacement; Carbapenem-resistant Enterobacteriaceae; Ebselen; New Delhi metallo-β-lactamase inhibitors.
In the present study, by employing the concept of bioisosteric replacement of the selenium moiety of ebselen, a small compound library of 2-substituted 1,2-benzisothiazol-3(2H)-ones, compounds I [R = 4-lCC6H4, 4-HOCH2C6H4, cyclohexyl, etc.] were designed, synthesized and evaluated their cytotoxicity and synergistic activity in combination with meropenem against the E. coli Tg1 (NDM-1) strain. The most promising compound I [R = 4-lCC6H4] demonstrated potent synergistic activity against a panel of clin. isolated NDM-1 pos. CRE strains with FICI as low as 0.09. Moreover, its IC50 value and inhibition mechanism were also confirmed by using the enzyme inhibition assay and the ESI-MS anal. resp. Importantly, compound I [R = 4-lCC6H4] has acceptable toxicity and is not a PAINS. Because of its structural simplicity and potent synergistic activity in combination with meropenem, we propose that compound 3a may be a promising meropenem adjuvant and a new series of such compounds may worth further investigations.
Bioorganic Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 21725-69-9 belongs to class isoxazole, and the molecular formula is C7H5NO2, Synthetic Route of 21725-69-9.
Referemce:
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem