Synthesis and antibacterial activity of 6-ethylsulfonyl-3-acylmethylene-1,4-benzoxazin-2-ones

Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: Novel antibacterial agents against Mycobacterium tuberculosis

“…In addition, the MIC values increased 5-fold for 14 and 16 , and 2.5-fold for 17 , (Table 3), compared to the analogous compounds in Table 2, suggesting that while a portion of their antibacterial activity could stem from an ability to inhibit MenB, there must be additional targets for these compounds in the cell. Many antibacterial benzoxazines previously reported also have bulky side chains and relatively poor activity against M. tuberculosis 19 as well as other bacteria 17, 20. Thus, again we would suggest that activity might be improved in the latter cases by reducing the size of the side chain.…”

“…Since the methyl group is electron donating, we speculate that the effect on activity results primarily from the size of the substituent and not from electronic effects. Interestingly, a series of benzoxazines bearing an ethylsulfonyl group (similar to compound 7 ), had poor antibacterial activity against E. coli and S. aureus ,17 raising the possibility that a reduction in substituent size in the latter case might lead to an increase in compound activity. The data in Table 2 also demonstrate that the benzoxazine core is essential for antibacterial activity as well as enzyme inhibition, since compounds with quinoxaline ( 12 ) or benzothiozine ( 13 ) cores had greatly reduced MIC and IC 50 values compared to the parent compounds.…”

Benzoylpyruvates in heterocyclic chemistry

“…Cyclic N,O ‐dinucleophiles appended by a two‐unit linker are restricted to 2‐aminophenols. Thus, when a benzoylpyruvate 55 reacts with 2‐aminophenol 67 itself, the result is formation of the corresponding 1,4‐benzoxazine‐2‐one 68 (Scheme ) [46–48].…”

Reaction of substituted o-aminophenols with acylpyruvic acid esters and α-ketoglutaric acid. Antibacterial activity of the products

“…Several of these compounds and their derivatives possess various types of biological activity [2,3]. We have previously studied the reaction of methyl esters of acylpyruvic acids with 2-amino-4-ethylsulfonylphenol and shown that 6-ethylsulfonyl-3-acylmethylene-1,4-benzoxazin-2-ones that possess antimicrobial activity were formed [4]. In continuation of the search for biologically active compounds among substituted benzoxazin-2-ones and their derivatives, we synthesized compounds of this series containing a methyl and Cl in the 6-position and a nitro and methyl in the 7-position.…”