88824-37-7Relevant academic research and scientific papers
Structure-based development of (1-(3′-Mercaptopropanamido)methyl)boronic Acid Derived Broad-Spectrum, Dual-Action Inhibitors of Metallo- And Serine-β-lactamases
Wang, Yao-Ling,Liu, Sha,Yu, Zhu-Jun,Lei, Yuan,Huang, Meng-Yi,Yan, Yu-Hang,Ma, Qiang,Zheng, Yang,Deng, Hui,Sun, Ying,Wu, Chengyong,Yu, Yamei,Chen, Qiang,Wang, Zhenling,Wu, Yong,Li, Guo-Bo
, p. 7160 - 7184 (2019/08/28)
The emergence and spread of bacterial pathogens acquired metallo-β-lactamase (MBL) and serine-β-lactamase (SBL) medicated β-lactam resistance gives rise to an urgent need for the development of new dual-action MBL/SBL inhibitors. Application of a pharmacophore fusion strategy led to the identification of (2′S)-(1-(3′-mercapto-2′-methylpropanamido)methyl)boronic acid (MS01) as a new dual-action inhibitor, which manifests broad-spectrum inhibition to representative MBL/SBL enzymes, including the widespread VIM-2 and KPC-2. Guided by the VIM-2:MS01 and KPC-2:MS01 complex structures, further structural optimization yielded new, more potent dual-action inhibitors. Selectivity studies indicated that the inhibitors had no apparent inhibition to human angiotensin-converting enzyme-2 and showed selectivity across serine hydrolyases in E. coli and human HEK293T cells labeled by the activity-based probe TAMRA-FP. Moreover, the inhibitors displayed potentiation of meropenem efficacy against MBL- or SBL-positive clinical isolates without apparent cytotoxicity. This work will aid efforts to develop new types of clinically useful dual-action inhibitors targeting MBL/SBL enzymes.
Synthesis of 1-amino-2-phenylethane-1-boronic acid derivatives
Matteson, Donald S.,Sadhu, Kizhakethil Mathew
, p. 614 - 618 (2008/10/08)
The boron analogue of N-acetylphenylalanine, (R)-1-acetamido-2-phenylethane-1-boronic acid (5b), has been synthesized from (+)-pinanediol phenylmethane-1-boronate (1b), which was converted by (dichloromethyl)lithium to the (S)-1-chloro-2-phenylethane-1-boronate (2b), then with N-lithiohexamethyldisilazane to the silylated 1-amino-2-phenylethane-1-boronic ester 3b, which was desilylated and acetylated in situ to (+)-pinanediol (R)-1-acetamido-2-phenylethane-1-boronate (4b) and then cleaved to the free boronic acid 5b with boron trichloride. 1-Amino-2-phenylethane-1-boronic esters (6) were found to be isolable but unstable, deboronating to 2-phenylethylamine under the influence of heat or hydroxylic solvents. 1-Amino-2-phenylethane-1-boronic acid, though not isolable, partially survives for an hour in cold aqueous solution. Attempts to synthesize the stable α-acetamido boronic esters (4) directly by reaction of lithioacetamide with 1-halo-2-phenylethane-1-boronic esters (2) have resulted in a major proportion of O-alkylation to form imino esters. Pinacol 1-acetamidino-2-phenylethane-1-boronate (8) has been obtained from the α-iodo boronic ester 2d and acetamidine.
