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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Antibacterial oxazolidinone analogues having a N-hydroxyacetyl-substituted seven-membered [1,2,5]triazepane or
Hideyuki Suzuki1, Iwao Utsunomiya, Koichi Shudo
1Research Foundation Itsuu Laboratory, 2-28-10 Tamagawa, Tokyo 158-0094, Japan. hsuzuki@itsuu.or.jp
Abstract:
We synthesized a series of oxazolidinone analogues bearing a N-hydroxyacetyl-substituted [1,2,5]triazepane or [1,2,5]oxadiazepane C-ring unit as homologues of an earlier drug candidate, eperezolid. Several of these compounds exhibited potent in vitro antibacterial activities towards not only Gram-positive, but also Gram-negative and linezolid-resistant pathogens. Compounds 21a and 21b, bearing a thiocarbamate side chain, showed high in vivo activity against methicillin-resistant Staphylococcus aureus SR3637, together with a promising safety profile in terms of weak inhibition of monoamine oxidase and cytochrome P450 isozymes.
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