Myxopyronin B analogs as inhibitors of RNA polymerase, synthesis and biological evaluation

Thomas Doundoulakis; Alan X Xiang; Ricardo Lira; Konstantinos A Agrios; Stephen E Webber; Wes Sisson; Robert M Aust; Amit M Shah; Richard E Showalter; James R Appleman; Klaus B Simonsen

doi:10.1016/j.bmcl.2004.08.045

Myxopyronin B analogs as inhibitors of RNA polymerase, synthesis and biological evaluation

Bioorg Med Chem Lett. 2004 Nov 15;14(22):5667-72. doi: 10.1016/j.bmcl.2004.08.045.

Authors

Thomas Doundoulakis¹, Alan X Xiang, Ricardo Lira, Konstantinos A Agrios, Stephen E Webber, Wes Sisson, Robert M Aust, Amit M Shah, Richard E Showalter, James R Appleman, Klaus B Simonsen

Affiliation

¹ Department of Medicinal Chemistry, Anadys Pharmaceuticals Inc., 3115 Merryfield Row, San Diego, CA 92121, USA.

PMID: 15482944
DOI: 10.1016/j.bmcl.2004.08.045

Abstract

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.

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / pharmacology*
DNA-Directed RNA Polymerases / antagonists & inhibitors*
Escherichia coli / drug effects
Evaluation Studies as Topic
Lactones / chemical synthesis*
Lactones / pharmacology*
Molecular Structure
Staphylococcus aureus / drug effects
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Lactones
myxopyronin B
DNA-Directed RNA Polymerases