Synthesis of benzo[b][1,4]oxazin-3(4H)-ones via smiles rearrangement for antimicrobial activity

Medicinal Chemistry Research (Impact Factor: 1.4). 07/2011; 20(6):670-677. DOI: 10.1007/s00044-010-9360-z


The benzo[b][1,4]oxazin-3(4H)-one derivs., e.g., I (R=-CH2Ph,cyclohexyl,hexyl) carrying F, Br, and Cl on the benzene ring, or benzyl, cyclohexyl, n-hexyl, and tetrafuryl methylene groups attached to nitrogen atom were synthesized via Smiles rearrangement and assayed in vitro for their antimicrobial activity against Gram-pos., Gram-neg. bacteria, and fungi. The antimicrobial activity of the benzo[b][1,4]oxazin-3(4H)-ones showed, on the whole, potency toward all the tested Gram-pos. and Gram-neg. microorganism (MIC ranging from 16 to 64 micro g/mL), whereas weak effectiveness was exhibited against fungi. Data obtained suggest that fluorine atom in the compds., I (R=-CH2Ph,cyclohexyl,hexyl) plays an important role in enhancing the antimicrobial properties of this class of compds. These observations provide some predictions to design further antimicrobial active compds. prior to their synthesis according to mol. modeling studies.

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    ABSTRACT: Novel 2H-benzo[b][1,4]oxazin-3(4H)-ones have been synthesized by condensation, reduction, O-alkylation and Smiles rearrangement using 3-bromo-4-hydroxy benzaldehyde, anilines, and chloroacetyl chloride as starting materials. All the synthesized compounds have been characterized by (1)H NMR, (13)C NMR, and HRMS, and tested for the inhibitory ability on platelet aggregation. The results have shown that the ADP (adenosine 5'-diphosphate)-induced platelet aggregation was inhibited by 7a-g with the IC(50) value at 10.14-18.83 μmol/L. Compound 7a exhibited the most potent inhibitory effect (IC(50)=10.14 μmol/L) among all the compounds, but less potent than the control drug ticlopidine (3.18 μmol/L) and aspirin (6.07 μmol/L). The preliminary structure-activity relationship (SAR) was initially investigated in the study.
    Bioorganic & medicinal chemistry letters 11/2011; 22(1):204-6. DOI:10.1016/j.bmcl.2011.11.027 · 2.42 Impact Factor