Preparation and in vitro anti-staphylococcal activity of novel 11-deoxy-11-hydroxyiminorifamycins.
We report herein the preparation and anti-staphylococcal activity of a series of novel 11-deoxy-11-hydroxyiminorifamycins. Many of the compounds synthesized exhibit potent activity against wild-type Staphylococcus aureus with MICs equivalent to, or better than, rifamycin reference agents. In addition, some of the compounds retain potent activity against an intermediate rifamycin-resistant strain of Staphylococcus aureus. For instance, compound 5k exhibits an MIC of 0.12 microg/mL against an intermediate rifamycin-resistant strain, while the rifamycin reference agents, rifampin and rifalazil, exhibit MICs of 16 microg/mL and 2 microg/mL, respectively, against the same strain.
Li
Jing
J
Department of Medicinal Chemistry, Cumbre Pharmaceuticals Inc., 1502 Viceroy Drive, Dallas, TX 75235, USA.
Ma
Zhenkun
Z
Chapo
Katrina
K
Yan
Dalai
D
Lynch
A Simon
AS
Ding
Charles Z
CZ
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006900:Hydroxylation; D007097:Imines / Q000737:chemistry*; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D012294:Rifamycins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship