title: Synthesis and antibacterial evaluation of a novel series of rifabutin-like spirorifamycins.
abstract: A novel series of spirorifamycins was synthesized and their antibacterial activity evaluated both in vitro and in vivo. This new series of rifamycins shows excellent activity against Staphylococcus aureus that is equivalent to rifabutin. However, some compounds of the series exhibit lower MICs than rifabutin against rifampin-resistant strains of S. aureus. Further, compound 2e exhibits comparable efficacy in vivo in a murine model of S. aureus septicemia model following administration by either oral or parenteral dosing routes.
authors.affiliation: Department of Medicinal Chemistry, Cumbre Pharmaceuticals Inc., 1502 Viceroy Dr., Dallas, TX 75235, USA.
authors.forename: In Ho
authors.initials: IH
authors.lastname: Kim
authors.forename: Keith D
authors.initials: KD
authors.lastname: Combrink
authors.forename: Zhenkun
authors.initials: Z
authors.lastname: Ma
authors.forename: Katrina
authors.initials: K
authors.lastname: Chapo
authors.forename: Dalai
authors.initials: D
authors.lastname: Yan
authors.forename: Paul
authors.initials: P
authors.lastname: Renick
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Morris
authors.forename: Mark
authors.initials: M
authors.lastname: Pulse
authors.forename: Jerry W
authors.initials: JW
authors.lastname: Simecka
authors.forename: Charles Z
authors.initials: CZ
authors.lastname: Ding
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D004333:Drug Administration Routes; D051379:Mice; D008826:Microbial Sensitivity Tests; D017828:Rifabutin / Q000138:chemical synthesis* / Q000494:pharmacology*; D012294:Rifamycins / Q000138:chemical synthesis / Q000494:pharmacology; D018805:Sepsis / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D012294:Rifamycins; D017828:Rifabutin