Oga inhibitor compounds

A method of treating or preventing a tauopathy, or an alpha synucleinopathy, comprising:

• administering to a subject in need thereof a prophylactically or therapeutically effective amount of a compound of Formula (I)
• or a tautomer or a stereoisomeric form thereof, wherein
• R1 is selected from the group consisting of —C1-4alkyl-C(═O)NRxRy C1-6alkyl optionally substituted with one or more substituents, each independently selected from the group consisting of halo, —CN, —OC1-4alkyl, OH, oxazolyl, C3-6cycloalkyl optionally substituted with one or more independently selected halo substituents;
• with the proviso that a —OC1-4alkyl or —OH substituent, when present, is at least two carbon atoms away from the nitrogen atom of the bicyclic core;
• wherein Rx and Ry are each independently selected from the group consisting of hydrogen, C1-4 alkyl, monohaloC1-4alkyl, polyhaloC1-4alkyl, and C3-6cycloalkyl;
• or Rx and Ry together with the nitrogen atom to which they are attached form a heterocyclyl ring selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl;
• R2 and R4 when present, are each independently selected from the group consisting of hydrogen, halo, C1-4alkyl and C3-6cycloalkyl;
• and
• R3 is a 5- or 6-membered monocyclic aryl or heteroaryl radical selected from the group consisting of pyrazolyl, phenyl and pyridyl;
• each of which is substituted with one or more substituents, each independently selected from the group consisting of halo, C1-4alkyl, —CN, monohaloC1-4alkyl, polyhaloC1-4alkyl, C1-4alkyloxy, monohaloC1-4alkyloxy, polyhaloC1-4alkyloxy, —(C═O)C1-4alkyl, and Het;
• and wherein at least one substituent is positioned at the carbon atom ortho- to the NH linker binding R4 to the bicyclic core;
• wherein
• Het is selected from the group consisting of pyrazolyl, phenyl, pyridyl optionally substituted with one or more substituents, each independently selected from the group consisting of halo, C1-4alkyl, —CN, C1-4alkyloxy;
• or a pharmaceutically acceptable addition salt or a solvate thereof.

A method for inhibiting O-GlcNAc hydrolase, comprising:

• administering to a subject in need thereof, a prophylactically or a therapeutically effective amount of a compound of Formula (I)
• or a tautomer or a stereoisomeric form thereof, wherein
• R1 is selected from the group consisting of —C1-4alkyl-C(═O)NRxRy;
• C1-6alkyl optionally substituted with one or more substituents, each independently selected from the group consisting of halo, —CN, —OC1-4alkyl, OH, oxazolyl, C3-6cycloalkyl optionally substituted with one or more independently selected halo substituents;
• with the proviso that a —OC1-4alkyl or —OH substituent, when present, is at least two carbon atoms away from the nitrogen atom of the bicyclic core;
• wherein Rx and Ry are each independently selected from the group consisting of hydrogen, C1-4 alkyl, monohaloC1-4alkyl, polyhaloC1-4alkyl, and C3-6cycloalkyl;
• or Rx and Ry together with the nitrogen atom to which they are attached form a heterocyclyl ring selected from the group consisting of azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl and morpholinyl;
• R2 and R4 when present, are each independently selected from the group consisting of hydrogen, halo, C1-4alkyl and C3-6cycloalkyl;
• and
• R3 is a 5- or 6-membered monocyclic aryl or heteroaryl radical selected from the group consisting of pyrazolyl, phenyl and pyridyl;
• each of which is substituted with one or more substituents, each independently selected from the group consisting of halo, C1-4alkyl, —CN, monohaloC1-4alkyl, polyhaloC1-4alkyl, C1-4alkyloxy, monohaloC1-4alkyloxy, polyhaloC1-4alkyloxy, —(C═O)C1-4alkyl, and Het;
• and wherein at least one substituent is positioned at the carbon atom ortho- to the NH linker binding R4 to the bicyclic core;
• wherein
• Het is selected from the group consisting of pyrazolyl, phenyl, pyridyl optionally substituted with one or more substituents, each independently selected from the group consisting of halo, C1-4alkyl, —CN, C1-4alkyloxy;
• or a pharmaceutically acceptable addition salt or a solvate thereof.