Myxopyronin B analogs as inhibitors of RNA polymerase, synthesis and biological evaluation.
A series of myxopyronin B analogs has been prepared via a convergent synthetic route and were tested for in vitro inhibitory activity against DNA-dependent RNA polymerase and antibacterial activity against E. coli and S. aureus. The parent lead compound proved to be very sensitive to even small changes. Only the achiral desmethyl myxopyronin B (1a) provided enhanced potency.
Doundoulakis
Thomas
T
Department of Medicinal Chemistry, Anadys Pharmaceuticals Inc., 3115 Merryfield Row, San Diego, CA 92121, USA.
Xiang
Alan X
AX
Lira
Ricardo
R
Agrios
Konstantinos A
KA
Webber
Stephen E
SE
Sisson
Wes
W
Aust
Robert M
RM
Shah
Amit M
AM
Showalter
Richard E
RE
Appleman
James R
JR
Simonsen
Klaus B
KB
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000187:drug effects; D005069:Evaluation Studies as Topic; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology*; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007783:Lactones; C040323:myxopyronin B; D012321:DNA-Directed RNA Polymerases