title: Synthesis and application of [1,2,5]triazepane and [1,2,5]oxadiazepane as versatile structural units for drug discovery.
abstract: 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 N-protected 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.
authors.affiliation: Research Foundation Itsuu Laboratory, Tokyo, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Iwao
authors.initials: I
authors.lastname: Utsunomiya
authors.forename: Koichi
authors.initials: K
authors.lastname: Shudo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D055808:Drug Discovery; D007275:Injections, Intravenous; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D001381:Azepines