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

Helperby Therapeutics Ltd

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 substituted 2,3-dihydro-1H-pyrrolo[3,2-c]quinoline derivatives and pharmaceutically acceptable salts. In particular, the disclosed compounds include 4-methyl-1-(2-phenylethyl)-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-c]-quinoline or a pharmaceutically acceptable salt thereof, and the compounds include pharmaceutically acceptable derivatives, including salts, solvates, N-oxides, and quaternary ammonium salts.

The compounds are described for use in killing clinically latent microorganisms and for treatment of protozoal diseases. Clinically latent microorganisms are described as viable/non-culturable microorganisms, phenotypically tolerant microorganisms, and metabolically active but slow-growing microorganisms, while protozoal disease use cases include Leishmania, Plasmodium, Trypanosoma, Giardia, coccidia/Cryptosporidium, Toxoplasma, Balantidium, amoebae such as Entamoeba, and Microsporidia.

The disclosure also addresses pharmaceutically acceptable formulations for administering the described compounds, including topical pharmaceutical compositions and combination products for topical administration. Combination concepts include the described compound or its salt together with a conventional antibiotic agent or an antimicrobial agent, formulated in admixture with a pharmaceutically acceptable adjuvant, diluent, or carrier.

The disclosure further describes therapeutic and non-therapeutic uses, including medicament preparations for latent killing and treatment of microbial infection, and ex vivo use as a sterilising agent and preservative. A kit-of-parts concept is also described.

Claims Coverage

The independent claim coverage centers on 2 specific inventive features: a pyrrolo[3,2-c]quinoline compound and a combination product with an antimicrobial agent. Dependent claim coverage adds hydrochloride salt narrowing and extends to carrier or topical administration elements, with selectable antimicrobial agents including telithromycin and other named antimicrobial options.

Coverage centers on the specific 4-methyl-1-(2-phenylethyl)-8-phenoxy-2,3-dihydro-1H-pyrrolo[3,2-c]quinoline, including hydrochloride, and extends to combination products with an antimicrobial agent formulated with a pharmaceutically acceptable adjuvant, diluent, or carrier, including topical administration.

Stated Advantages

Documented Applications