Modulation of pathogenicity

Abstract

The present invention relates to the use of compounds of the general Formula (XIII):

• • wherein
  • A⁷ is C═O, C═S, SO₂, CH—OR¹³, C═NR¹², or CH₂—CHOR¹³;
  • A⁸ is C(R¹⁴)₂, O, S, or NR¹²;
  • A⁹ is C═O, C═S, SO₂, CH—OR¹³, C═NR¹², or CH₂—CHOR¹³;
  • m is 0, or 1
  • q is 0, or 1
  • r is 0, or 1
  • R¹² is H, CH₃, CH₂—CH₃, C₆H₅, OCH₃, OCH₂—CH₃, OH, or SH;
  • R¹³ is H, CH₃, or CH₂—CH₃;
  • R¹⁴ is H, alkyl, alkoxy, OH, or SH;

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]The present application is a continuation of co-pending application Ser. No. 10 / 839,221, filed May 6, 2004, which is a continuation-in-part of application Ser. No. 10 / 429,875, filed May 6, 2003, which is a continuation in part of application Ser. No. 10 / 094,301, filed Mar. 8, 2002, now abandoned, the contents of each are herein incorporated by reference in their entirety.BACKGROUND OF THE INVENTION[0002]The present invention relates to the use of compounds such as amide, carbazide and hydrazide derivatives as selective inhibitors of bacterial pathogens. In particular the invention refers to a family of compounds that block the quorum sensing system of Gram-negative bacteria, a process for their manufacture, pharmaceutical compositions containing them and to their use for the treatment and prevention of microbial damages and diseases, in particular for diseases where there is an advantage in inhibiting quorum sensing regulated phenotypes o...

AI Technical Summary

Benefits of technology

[0018]Accordingly, we have been able to find compounds that can significantly reduce virulence gene expression and biofilm formation of several human pathogens. In contrast to the furanones the compounds of this invention do not show any toxic effect and are therefore suitable for applications in a wide area. Such applications could be the use of the compounds for instance as new antibiotic therapeutics, disinfectants, antifouling coatings or coatings of medical devices. In contrast to traditional antibacterial agents (like amide or 1,2-acylhydrazine derivatives in WO 01/51456; for the synthesis of amide or 1,2-acylhydrazine derivatives see also EP 638545 and EP 982292), the compound

Problems solved by technology

Many microorganisms, including bacteria, fungi, protozoa and algae cause severe damages or diseases in different areas such as industry, agriculture, environment and medicine.

Especially bacteria as human pathogens cause tremendous costs in public health systems worldwide.

The latter approach has, however, lacked specific targets for rational drug design.

Biofilms represent a severe problem as bacteria integrated in such a polymer matrix develop resistance to conventional antimicrobial agents.

Furthermore, microbial biofilms growing for example on ship hulls increase fuel consumption through enhanced frictional resistance and simultaneously reduce maneuverability.

Since biofi

Images