Non-lactone carbocyclic and heterocyclic antagonists and agonists of bacterial quorum sensing

Patent metadata

Field	Value
Publication number	US-9758472-B2
Application number	US-201314104235-A
Country	US
Kind code	B2
Filing date	Dec 12, 2013
Priority date	Jun 30, 2009
Publication date	Sep 12, 2017
Grant date	Sep 12, 2017

Abstract

Non-lactone carbocyclic and heterocyclic antagonists and agonists of bacterial quorum sensing. Pharmaceutical composition containing antagonists. Methods employing antagonists and agonists for modulation of quorum sensing. Compounds are exemplified by those of formula:

A-[Z] n -L1-[Y] q -W-[V] m -L2-HG,

where A is an acyclic aliphatic group, and HG is an optionally substituted phenyl group. Compounds include those where m and n are both 0, W is —NH—, Y is present and is —CO—CH 2 —CO—, and L1 and L2 independently are —[CH 2 ] p1 — and —[CH 2 ] p2 —, where p1 and p2, independently, are 0 or integers ranging from 1-10.

First claim

We claim:

1. A compound having formula:
A-CO—CH 2 —CO—NH—HG

wherein A is an unsubstituted alkyl group having 9 or 10 carbon atoms and HG is an unsubstituted phenyl group.

2. The compound of claim 1 wherein A is an unsubstituted straight-chain alkyl group having 9 carbon atoms.

3. A compound selected from:

4. A pharmaceutical composition comprising a quorum sensing antagonist of claim 1 in an amount effective for obtaining a therapeutic effect and a pharmaceutically acceptable carrier.

5. The composition of claim 4 further comprising an antimicrobial compound, an antibacterial compound, an antiviral agent or an antibiotic, other than a quorum sensing antagonist.

6. A method for inhibiting quorum sensing bacteria which comprising the step of contacting the quorum sensing bacteria with an amount of a quorum sensing compound of claim 1 effective for inhibition of quorum sensing.

7. The method of claim 6 wherein bacterial biofilm formation is disrupted which comprises the step of contacting the biofilm or an environment containing the biofilm with the compound of claim 1 .

Assignees

• Wisconsin Alumni Res Found

Inventors

• Blackwell Helen E
• Mcinnis Christine E

Classifications

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07C235/80

  having carbon atoms of carboxamide groups and keto groups bound to the same carbon atom, e.g. acetoacetamides · CPC title

• C07D231/40

  Acylated on said nitrogen atom · CPC title

• A61K31/404

  Indoles, e.g. pindolol · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title