Synthesis and antibacterial evaluation of a novel series of rifabutin-like spirorifamycins.
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.
Kim
In Ho
IH
Department of Medicinal Chemistry, Cumbre Pharmaceuticals Inc., 1502 Viceroy Dr., Dallas, TX 75235, USA.
Combrink
Keith D
KD
Ma
Zhenkun
Z
Chapo
Katrina
K
Yan
Dalai
D
Renick
Paul
P
Morris
Timothy W
TW
Pulse
Mark
M
Simecka
Jerry W
JW
Ding
Charles Z
CZ
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
D000900:Anti-Bacterial Agents; D012294:Rifamycins; D017828:Rifabutin