Oga inhibitor compounds
AssigneeJanssen Pharmaceutica NV
InventorsJosé Manuel Bartolomé-Nebreda, Andrés Avelino Trabanco-Suárez, Carlos Manuel Martinez Viturro
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Abstract
The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations.
Claims14
A compound of Formula (I)
- or a stereoisomeric form thereof, wherein
- m and n each independently represent 0 or 1, with the proviso that they are not both simultaneously 0;
- LA is a covalent bond or CHR;
- wherein
- R is hydrogen or C1-4alkyl optionally substituted with 1, 2 or 3 independently selected halo substituents;
- RA represents a 6-membered aryl or heteroaryl radical selected from the group consisting of phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazin-3-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, and pyrazin-2-yl, each of which may be optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo;
- cyano;
- C1-4alkyl optionally substituted with 1, 2 or 3 independently selected halo substituents;
- C3-7cycloalkyl;
- C1-4alkyloxy optionally substituted with 1, 2 or 3 independently selected halo substituents;
- and NRaRaa, wherein Ra is hydrogen or C1-4alkyl optionally substituted with 1, 2, or 3 independently selected halo substituents, and Raa is selected from the group consisting of hydrogen, C1-4alkyl optionally substituted with 1, 2, or 3 independently selected halo substituents, and
- —C(═O)C1-4alkyl;
- LB is CHR1;
- wherein R1 is hydrogen or C1-4alkyl optionally substituted with 1, 2 or 3 independently selected halo substituents;
- and
- RB represents a heterocyclic ring or ring system selected from the group consisting of (b-1), (b-2), (b-3), (b-4), (b-5), (b-6), (b-7), (b-8), (b-9), (b-10), (b-11) and (b-12):
- wherein
- Z1 is O, NR1z or S;
- wherein R1z is hydrogen or C1-4alkyl;
- Z2 and Z3 each independently represent CH or N;
- R3 is C1-4alkyl;
- R2, R4, R5 and R6 each independently represent hydrogen or C1-4alkyl;
- or
- -LB-RB is a radical of formula (b-13)
- wherein R7 is hydrogen or C1-4alkyl;
- or a pharmaceutically acceptable addition salt or a solvate thereof.
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A compound of Formula (II)
- or a stereoisomeric form thereof, wherein
- m and n each independently represent 0 or 1, with the proviso that they are not both simultaneously 0;
- LA is a covalent bond or CHR;
- wherein
- R is hydrogen or C1-4alkyl optionally substituted with 1, 2 or 3 independently selected halo substituents;
- and
- RA represents a 6-membered aryl or heteroaryl radical selected from the group consisting of phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyridazin-3-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, and pyrazin-2-yl, each of which may be optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halo;
- cyano;
- C1-4alkyl optionally substituted with 1, 2 or 3 independently selected halo substituents;
- C3-7cycloalkyl;
- C1-4alkyloxy optionally substituted with 1, 2 or 3 independently selected halo substituents;
- and NRaRaa, wherein Ra is hydrogen or C1-4alkyl optionally substituted with 1, 2, or 3 independently selected halo substituents, and Raa is selected from the group consisting of hydrogen, C1-4alkyl optionally substituted with 1, 2, or 3 independently selected halo substituents, and
- —C(═O)C1-4alkyl;
- or a pharmaceutically acceptable addition salt or a solvate thereof, for use as an OGA inhibitor.
Dependencies are inferred from the claim text.