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 document relates to substituted pyrrolo[3,2-c]quinoline compounds and 2,3-dihydro derivatives, including compounds according to Formula I and related Formulae Ia-Ic/Ib, for killing clinically latent microorganisms. Clinically latent microorganisms are described as viable but non-culturable and phenotypically tolerant, including low-growth and metabolically active microorganisms.

The document defines broad structural substitution patterns for pyrrolo[3,2-c]quinoline derivatives, including substituents R1, R2, R3, X and heterocyclic/aryl groups, together with exclusion lists of specific prior and undesired structures. The compounds are presented as members that are novel per se for certain formula members, alongside representative allowed compounds described within the structural families.

The invention is presented with multiple medicament and use aspects for treating infections. A medicament preparation is described for killing clinically latent microorganisms and treating microbial infections in mammals, including an ex vivo use described for sterilising and preservative purposes, and combination products with conventional antimicrobial agents to reduce the required dose of conventional antimicrobials.

Claims Coverage

Two independent claims are identified. Both claims rely on administering an effective amount of a selected compound from a large enumerated group of substituted 2,3-dihydro pyrrolo[3,2-c]quinoline derivatives (or pharmaceutically acceptable salts), with the key difference being whether the target is specified as clinically latent fungal microorganisms (killing method) or treatment of a microbial infection in general limited to fungal infection (treatment method).

Across both independent claims, the inventive scope is centered on administering enumerated substituted 2,3-dihydro pyrrolo[3,2-c]quinoline compounds (or pharmaceutically acceptable salts). The first claim additionally requires the microorganisms to be clinically latent and associated with a fungal infection, while the second claim requires only that the microbial infection be a fungal infection.

Stated Advantages

Documented Applications