Use of pyrroloquinoline compounds to kill clinically latent microorganisms
Inventors
Beck, Petra Helga • Brown, Marc Barry • Clark, David Edward • Coates, Anthony • Dyke, Hazel Joan • Hu, Yanmin • Londesbrough, Derek John • Mills, Keith • Pallin, Thomas David • Reid, Gary Patrick • Stoddart, Gerlinda
Assignees
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Publication Number
US-9694006-B2
Publication Date
2017-07-04
Expiration Date
Abstract
There is provided the use of compounds of formula I wherein R1, R2, R3 and X have meanings given in the description, for the preparation of a medicament for killing clinically latent microorganisms. There is also provided the use of compounds of formula I for treating microbial infections, as well as certain compounds of formula I per se.
Core Innovation
The invention relates to pyrrolo[3,2-c]quinoline and related 2,3-dihydro derivatives as compounds used to prepare medicaments for killing clinically latent microorganisms. Clinically latent microorganisms are described as viable but non-culturable microorganisms and phenotypically tolerant microorganisms, including persisters and stationary-phase and biofilm-associated subpopulations. The medicaments are described for use in connection with clinically latent microorganisms associated with microbial infections in a mammal.
The disclosure provides a broad chemical scope for compounds of formula I and includes specified heterocyclic and aryl substituents, along with excluded or non-covered example substructures. It also includes pharmaceutically acceptable derivatives, including salts, solvates, quaternary ammonium salts and N-oxides, and describes certain compounds as novel per se as formula I, Ia, Ib, and Ic.
The invention expands therapeutic scope to treating microbial infections, including bacterial infections and fungal infections, and the document also lists organism classes including protozoa. It further describes non-therapeutic uses including sterilisation and preservation, and combination products or kits with conventional antibiotic agents or sterilising agents.
Claims Coverage
The consolidated independent claims include four inventive claim sets. They cover killing clinically latent microorganisms and treating microbial infections in a mammal, with the microbial indication narrowed at the independent-claim level to bacterial infection, fungal infection caused by Candida, and an infection disease panel. Across the claim sets, the core coverage is administering an effective amount of an enumerated substituted pyrrolo[3,2-c]quinoline derivative compound.
Killing clinically latent bacterial microorganisms by administering selected pyrrolo[3,2-c]-quinolines
Administering to a mammal in need thereof a compound selected from the enumerated substituted 2,3-dihydro-1H-pyrrolo[3,2-c]-quinolines and related salts, wherein the clinically latent microorganisms are associated with a bacterial infection.
Treating a microbial infection in a mammal with selected pyrrolo[3,2-c]-quinolines for bacterial infection
Administering to a mammal in need thereof an effective amount of a compound selected from the enumerated substituted 2,3-dihydro-1H-pyrrolo[3,2-c]-quinolines and related structures, wherein the microbial infection is a bacterial infection.
Treating an afflicted mammal disease by administering selected pyrrolo[3,2-c]-quinolines
Administering to an afflicted mammal an effective amount of a compound selected from the enumerated substituted 2,3-dihydro-1H-pyrrolo[3,2-c]-quinolines, wherein the disease is an infection with listed bacterial species including S. aureus, Enterococcus, Pseudomonas, MRSA, Klebsiella aerogrenes, E. coli, Streptococcus pneumoniae, Streptococcus pyogenes Group A Streptococci, Group B streptococci (Streptococcus agalactiae), Streptococcus viridans, Haemophilus influenzae, or M. tuberculosis.
Killing clinically latent fungal microorganisms by administering selected pyrrolo[3,2-c]-quinolines for Candida-associated infection
Administering to a mammal in need thereof a compound selected from the enumerated substituted 2,3-dihydro-1H-pyrrolo[3,2-c]-quinolines and related salts, wherein the clinically latent microorganisms are associated with a fungal infection caused by Candida.
The independent claims are directed to administering enumerated substituted pyrrolo[3,2-c]quinoline compounds to a mammal to kill clinically latent microorganisms or treat microbial infections. The microbial target is specified as clinically latent microorganisms associated with bacterial infection, bacterial infection, an infection disease panel, or a fungal infection caused by Candida.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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