- Synthesis and application of [1,2,5]triazepane and [1,2,5]oxadiazepane as versatile structural units for drug discovery
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Seven-membered heterocyclic [1,2,5]triazepane and [1,2,5]-oxadiazepane derivatives were synthesized as candidate structures for application in drug discovery in place of conventional piperazine or morpholine moieties, offering multiple sites for modification with functional groups. We first synthesized the Nprotected heterocycles, and then confirmed their utility by synthesizing analogues of the oxazolidinone antibacterial agent linezolid. The analogues exhibited potent in vitro and in vivo antibacterial activity. In particular, compound 10a exhibited good in vivo efficacy when administered intravenously in a murine model of systemic infection with methicillin-resistant Staphylococcus aureus SR3637. These seven-membered heterocycles are expected to be versatile structural units for drug discovery.
- Suzuki, Hideyuki,Utsunomiya, Iwao,Shudo, Koichi
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scheme or table
p. 1001 - 1002
(2010/09/17)
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- OXAZOLIDINONE DERIVATIVE HAVING 7-MEMBERED HETERO RING
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The present invention provides a novel oxazolidinone derivative of the formula (I): wherein Ring A is (A-1) a 7-membered monocyclic heterocycle containing three N atoms; (A-2) a 7-membered monocyclic heterocycle containing two N atoms and one O atom; or (A-3) a 7-membered monocyclic heterocycle containing two N atoms and one S atom, SO or SO2, wherein said monocyclic heterocycle is optionally substituted, optionally unsaturated and optionally fused with another ring; X1 is a single bond, or a heteroatom-containing group selected from the group consisting of -O-, -S-, -NR2-, -CO-, -CS-, -CONR3-, -NR4CO-, -SO2NR5-, and -NR6SO2-, wherein R2, R3, R4, R5 and R6 are independently hydrogen or lower alkyl, or lower alkylene or lower alkenylene each optionally interrupted by said heteroatom-containing group; Ring B is optionally substituted carbocycle or optionally substituted heterocycle; and R1 is hydrogen, or an organic residue which is able to bind to the 5-position of the oxazolidinone ring in oxazolidinone antimicrobial agents, pharmaceutically acceptable salts and solvates thereof which are useful as an antibacterial agent.
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Page/Page column 198
(2010/08/07)
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