Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Substituted polyamines as inhibitors of bacterial efflux pumps

a technology of bacterial efflux pump and substituted polyamine, which is applied in the direction of antibiotics, drug compositions, applications, etc., can solve problems such as therapeutic failures, and achieve the effects of increasing susceptibility to drugs, decreasing the translocation of these agents, and increasing the affinity of nitrogenous substrates

Inactive Publication Date: 2011-09-08
PARATEK PHARM INC
View PDF7 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The invention provides compounds that can inhibit the growth and infection of microbes by blocking the activity of efflux pumps. These compounds can be used alone or in combination with other drugs to treat bacterial infections and reduce the virulence of microbes. The invention also includes methods for enhancing the antimicrobial activity of drugs and pharmaceutical compositions containing the inhibitor compounds. The invention can help address the growing problem of multidrug-resistant bacteria and can be used in combination with other drugs to increase their effectiveness.

Problems solved by technology

Drug efflux proteins in microbes can mediate resistance causing therapeutic failures.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Substituted polyamines as inhibitors of bacterial efflux pumps
  • Substituted polyamines as inhibitors of bacterial efflux pumps
  • Substituted polyamines as inhibitors of bacterial efflux pumps

Examples

Experimental program
Comparison scheme
Effect test

example 1

Preparation of Substituted Polyamines

[0151]In general, polyamines may be derivatized using by, e.g., reductive amination with aryl aldehydes. Suitable polyamines include spermidine, spermine, norspermidine, spergaulin, 1,3,5-triamimocyclohexane, agrbactin, acyria pigments, and other products possessing 2 or more chemically modifiable amines. The polyamine substitution pattern may reside on one, two or three or more ring systems interconnected and in any pattern in a 3-D array.

[0152]For example, paromomycin derivatives (FIG. 2 and Table 2) are aminoglycosides possessing five primary amino functional groups (FIG. 1 and Table 1) and were produced by 5-N-benzylation using unsubstituted or substituted benzaldehydes under reduction by sodium borohydride. Many of these polysubstituted paromomycins are substrates of the efflux system of Haemophilus influenzae (Table 3) and act in synergy with tetracycline, doxycycline, and gentamicin to increase antibiotic susceptibility in H. influenzae (T...

example 2

Susceptibility of Haemophilus influenzae to Various Paromomycin Derivatives

[0155]AcrAB deleted strains of H. influenzae were constructed (see, e.g., Provence, D. L. and R. Curtiss III. (1994) In P. Gerhardt, R. G. E. Murray, W. A. Wood, and N. R. Krieg. (ed.), “Methods for General and Molecular Bacteriology,” American Society for Microbiology, Washington. pp. 317-347). Deletion of acrAB was confirmed by the absence of intact target DNA in a PCR assay.

[0156]MICs of selected antimicrobial agents were determined by a standard broth microdilution procedure with cation adjusted Mueller Hinton broth (Becton Dickinson, Cockeysville, Md.) and an inoculum of 5×105 CFU / ml according to NCCLS performance and interpretive guidelines (NCCLS. 1997. Methods for dilution antimicrobial susceptibility. Tests for bacteria that grow aerobically, Fourth Edition; Approved Standard. NCCLS document M7 A4 (ISBN 1 56238 309 4). NCCLS, 940 West Valley Road, Suite 1400, Wayne, Pa. 19087). Antimicrobial agents t...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
melting temperature Tmaaaaaaaaaa
melting temperature Tmaaaaaaaaaa
Tmaaaaaaaaaa
Login to View More

Abstract

Disclosed are methods of treating bacterial infections including those caused by multidrug resistant bacteria using polyamine efflux pump inhibiting compounds, including for example N-benzylated polyazaalkanes, N-benzylated polyaminoalkanes, or mixed N-benzylated poly(aza / amino)alkanes, optionally in combination with other drugs such as antibiotics, as well as pharmaceutical compositions thereof.

Description

RELATED APPLICATIONS[0001]This application is a continuation application of U.S. application Ser. No. 10 / 754,041, filed on Jan. 7, 2004, issuing; which claims priority to U.S. Provisional Patent Application No. 60 / 438,754, “Substituted Polyamines as Inhibitors of Bacterial Efflux Pumps” filed on Jan. 8, 2003, U.S. Provisional Patent Application No. 60 / 438,653, “Substituted Polyamines as Inhibitors of Bacterial Efflux Pumps” filed on Jan. 8, 2003, and to U.S. Provisional Patent Application No. 60 / 438,725, “Substituted Polyamines as Inhibitors of Bacterial Efflux Pumps” filed on Jan. 7, 2003. The entire contents of each of these patent applications are hereby incorporated herein by reference in their entirety.BACKGROUND[0002]Microbes have developed several different mechanisms of resistance to antibiotics and chemotherapeutic agents. These mechanisms of resistance can be specific, e.g., for a molecule or a family of molecules (e.g., antibiotics), or can be non-specific and be involved...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/706A61K31/7036A61P31/00A61P31/16C12N1/00C07G11/00A61K31/00A61K31/132A61K31/133A61K31/70
CPCA61K31/00A61K31/132A61K31/133A61K31/70A61K31/7036A61K2300/00A61P31/00A61P31/16Y02A50/30
Inventor NELSON, MARK L.ALEKSHUN, MICHAEL N.
Owner PARATEK PHARM INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com