PEPTIDE-BASED QUORUM SENSING INHIBITORS FOR THE ATTENUATION OF VIRULENCE IN STAPHYLOCOCCUS AUREUS

摘要

Compounds that affect quorum sensing (QS) in Staphylococcus aureus and related Staphylococcus species (e.g., S. epidermidis). Compounds which modulate one or more of the four AgrC receptors of Staphylococcus species, particularly of Staphylococcus aureus. Modulation includes inhibition or activation of one or more of these four AgrC receptors. These compounds are useful for bacterial interference and are useful for treating bacterial infections, particularly staphylococcal infection. Treatment can include combination of one or more of the compounds of the invention in combination with one or more antibiotics.

主权项

1. A compound of formula:and salts thereof where:
L is a divalent linker moiety 3 to 10 atoms in length; Z is a divalent linker moiety 3 to 12 atoms in length; R1 and R2 are independently selected from hydrogen, an optionally substituted alkyl group having 1-6 carbon atoms, an optionally substituted aryl group or an optionally substituted heteroaryl group; R6 and R7 are independently selected from hydrogen, an optionally substituted alkyl group having 1-8 carbon atoms, an optionally substituted aryl group or an optionally substituted heteroaryl group; where, when R1 is a group other than hydrogen or a methyl group, R6 is a hydrogen or a methyl group and when R2 is a group other than hydrogen or a methyl group, R7 is a hydrogen or a methyl group; R10 is hydrogen or a methyl group; R5 is an optionally substituted alkyl group having 1-8 carbon atoms, an optionally substituted aryl group, an optionally substituted heteroaryl group or R5 is:
H2N—CHR12—, H2N—CHR12—CO—NR14—, H2N—CHR12—CO—NR14—CHR12—, R15—CO—NR14—, or R15—CO—NR14—CHR12, where each R12 is hydrogen, an optionally substituted alkyl group having 1-6 carbon atoms, an optionally substituted aryl group or an optionally substituted heteroaryl group; R14 is hydrogen, an optionally substituted alkyl group having 1-8 carbon atoms, an optionally substituted aryl group or an optionally substituted heteroaryl group; and R15 is an optionally substituted alkyl group having 1-8 carbon atoms, an optionally substituted aryl group or an optionally substituted heteroaryl group where, when R5 is H2N—CHR12—CO—NR14— and R12 is a group other than hydrogen or a methyl, R14 is hydrogen or a methyl group.