The present invention relates to solid phase pharmaceutical compositions of 6-fluoro-N-(4-fluorobenzyl)-4-oxo-3,4-dihydro-1H-spiro[piperidine-4,2-quinoline]-1-carboxamide that is useful as a AKR1C3 dependent KARS inhibitor. The present invention also relates to processes for the preparation of said pharmaceutical compositions of said compound, methods of using said pharmaceutical compositions in the treatment of various diseases and disorders, and their use in diseases and disorders mediated by an AKR1C3 dependent KARS inhibitor.

The present invention relates to solid phase pharmaceutical compositions of 6-fluoro-N-(4-fluorobenzyl)-4-oxo-3,4-dihydro-1H-spiro[piperidine-4,2-quinoline]-1-carboxamide that is useful as a AKR1C3 dependent KARS inhibitor. The present invention also relates to processes for the preparation of said pharmaceutical compositions of said compound, methods of using said pharmaceutical compositions in the treatment of various diseases and disorders, and their use in diseases and disorders mediated by an AKR1C3 dependent KARS inhibitor.

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The present invention concerns new tricyclic spirolactams (TriSLas) compounds and their use as a drug, in particular for the prevention and/or treatment of a mycobacterial infection or for the treatment of a disease caused by infection with a Mycobacterium. The tuberculosis drug development pipeline requires further supplementation with additional candidates, ideally acting on novel targets (to minimize cross-resistance) and impacting on drug-tolerant bacilli to shorten treatment. The inventors of the present invention have identified new tricyclic spirolactams (TriSLas) compounds with particular activity against M. tuberculosis.

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The present invention concerns new tricyclic spirolactams (TriSLas) compounds and their use as a drug, in particular for the prevention and/or treatment of a mycobacterial infection or for the treatment of a disease caused by infection with a Mycobacterium. The tuberculosis drug development pipeline requires further supplementation with additional candidates, ideally acting on novel targets (to minimize cross-resistance) and impacting on drug-tolerant bacilli to shorten treatment. The inventors of the present invention have identified new tricyclic spirolactams (TriSLas) compounds with particular activity against M. tuberculosis.

The present invention relates to methods of identifying a subject for treatment with or treating a subject with a tricyclic AKR1C3 dependent KARS inhibitor of formula (I), or a pharmaceutically acceptable salt thereof. The methods may comprise determining in a subject sample a level of at least one of the following biomarkers: AKR1C3, NFE2L2, KEAP1, or CUL3, wherein an elevated level of the biomarker identifies the subject as being in need of treatment; or detecting in a subject sample a somatic mutation in at least one of the following genes: NFE2L2, KEAP1, or CUL3, wherein detecting the somatic mutation identifies the subject as being in need of treatment.

The present invention relates to methods of identifying a subject for treatment with or treating a subject with a tricyclic AKR1C3 dependent KARS inhibitor of formula (I), or a pharmaceutically acceptable salt thereof. The methods may comprise determining in a subject sample a level of at least one of the following biomarkers: AKR1C3, NFE2L2, KEAP1, or CUL3, wherein an elevated level of the biomarker identifies the subject as being in need of treatment; or detecting in a subject sample a somatic mutation in at least one of the following genes: NFE2L2, KEAP1, or CUL3, wherein detecting the somatic mutation identifies the subject as being in need of treatment.