The present invention relates to novel spiro-quinazolinone derivatives as positive allosteric modulators for modulating metabotropic glutamate receptor subtype 4 (mGluR4) and/or altering glutamate level or glutamatergic signalling.

The present invention relates to compounds of formula (I) ##STR00001##
or a pharmaceutically acceptable salt form thereof, wherein the substituents are as defined in the specification; to intermediates in the preparation of the compounds, to pharmaceutical compositions comprising the compounds and to the use of the compounds in the treatment of disease.

The present invention relates to compounds of formula (I) ##STR00001##
or a pharmaceutically acceptable salt form thereof, wherein the substituents are as defined in the specification; to intermediates in the preparation of the compounds, to pharmaceutical compositions comprising the compounds and to the use of the compounds in the treatment of disease.

The present embodiments relate to compounds with physiological effects, such as the activation of hematopoietic growth factor receptors. The present embodiments also relate to use of the compounds to treat a variety of conditions, diseases and ailments such as hematopoietic conditions and disorders.

The present embodiments relate to compounds with physiological effects, such as the activation of hematopoietic growth factor receptors. The present embodiments also relate to use of the compounds to treat a variety of conditions, diseases and ailments such as hematopoietic conditions and disorders.

Pharmaceutical compositions for oral administration comprising the drug substance (S)-1-chloro-8-(difluoromethoxy)-8,8-difluoro-6-(trifluoromethyl)-7,8-dihydro-3H,6H-spiro[imidazo[1,2-]pyridine-2,5-isoquinoline], or a pharmaceutically acceptable salt thereof, or a free form thereof are described. Further, processes for preparing said pharmaceutical 5 compositions for oral administration and uses of said pharmaceutical compositions in the manufacture of a medicament are described.

Pharmaceutical compositions for oral administration comprising the drug substance (S)-1-chloro-8-(difluoromethoxy)-8,8-difluoro-6-(trifluoromethyl)-7,8-dihydro-3H,6H-spiro[imidazo[1,2-]pyridine-2,5-isoquinoline], or a pharmaceutically acceptable salt thereof, or a free form thereof are described. Further, processes for preparing said pharmaceutical 5 compositions for oral administration and uses of said pharmaceutical compositions in the manufacture of a medicament are described.

The present invention relates to novel tricyclic compounds that are AKR1C3 dependent KARS inhibitor, processes for their preparation, pharmaceutical compositions, and medicaments containing them, and their use in diseases and disorders mediated by an AKR1C3 dependent KARS inhibitor.

A method for treating BRCA gene-mutated cancer. In the method, a drug containing hypoxia-activated prodrug compounds of formulas (1), (2) and (3) or AKR1C3 enzyme-activated prodrug compounds of formulas (4), (5), (6), (7), (8), (9), (10), (11) and (12) and salts, esters, solvates and isotopic isomers thereof, is used alone or in combination with other drugs to treat patients with BRCA gene-mutated cancer and tumors.

A method for treating BRCA gene-mutated cancer. In the method, a drug containing hypoxia-activated prodrug compounds of formulas (1), (2) and (3) or AKR1C3 enzyme-activated prodrug compounds of formulas (4), (5), (6), (7), (8), (9), (10), (11) and (12) and salts, esters, solvates and isotopic isomers thereof, is used alone or in combination with other drugs to treat patients with BRCA gene-mutated cancer and tumors.