Heteroaryl compounds and their use

A method of treating or preventing a lysosomal storage disease, comprising administering to a patient in need thereof an effective amount of a compound of formula (I):

• or a pharmaceutically acceptable salt or solvate thereof, wherein
• A1, A2, and A3 are each independently selected from the group consisting of N, CH and C(R4), provided that at least one of A1, A2, or A3 is N;
• each R4 is independent selected from the group consisting of halogen, —C1-4 alkyl, —C1-4 alkoxy, and —CN;
• n is 1 or 2, wherein the alkylene chain can be optionally substituted with one or more —C1-4 alkyl groups;
• R1 is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, and —C(═O)Ra, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, optionally substituted —O—(C6-10 aryl);
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• and
• R2 is selected from the group consisting of hydrogen, —C1-4 alkyl, and —C3-6 cycloalkyl, wherein said —C1-4 alkyl is optionally substituted with —O(C1-4)alkyl optionally substituted with —O(C1-4)NH2, hydroxy, —CN, halogen, or —N(Rb)2;
• or
• R1 and R2 together with the nitrogen atom to which they are attached form an optionally substituted 5- to 10-membered heterocyclic ring, wherein said heterocyclic ring optionally contains 1, 2, or 3 additional heteroatoms selected from the group consisting of N, S, or O, and wherein said heterocyclic ring is optionally fused to a phenyl ring;
• Ra is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, and —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, and -(5- to 10-membered)-C2-9 heterocyclyl;
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• each Rb is independently hydrogen, —C1-4 alkyl, —C3-10 cycloalkyl, or -(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl or heterocyclyl group is optionally substituted by 1, 2 or 3 fluorine atoms;
• and
• R3 is selected from the group consisting of —C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C3-10 cycloalkyl, and -(5- to 10-membered)-C2-9 heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, —ORb, and —N(Rb)2, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl and -(5- to 10-membered)-C2-9 heterocyclyl, and wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl is optionally fused to a further (second) ring.

A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment or prevention of lysosomal storage disease, the compound of formula (I) having the structure:

• wherein
• A1, A2, and A3 are each independently selected from the group consisting of N, CH and C(R4), provided that at least one of A1, A2, or A3 is N;
• each R4 is independently selected from the group consisting of halogen, —C1-4 alkyl, —C1-4 alkoxy, and —CN;
• n is 1 or 2, wherein the alkylene chain can be optionally substituted with one or more —C1-4 alkyl groups;
• R1 is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, and —C(═O)Ra, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, optionally substituted —O—(C6-10 aryl);
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• and
• R2 is selected from the group consisting of hydrogen, —C1-4 alkyl, and —C3-6 cycloalkyl, wherein said —C1-4 alkyl is optionally substituted with —O(C1-4)alkyl optionally substituted with —O(C1-4)NH2, hydroxy, —CN, halogen, or —N(Rb)2;
• or
• R1 and R2 together with the nitrogen atom to which they are attached form an optionally substituted 5- to 10-membered heterocyclic ring, wherein said heterocyclic ring optionally contains 1, 2, or 3 additional heteroatoms selected from the group consisting of N, S, or O, and wherein said heterocyclic ring is optionally fused to a phenyl ring;
• Ra is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, and —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, and -(5- to 10-membered)-C2-9 heterocyclyl;
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• each Rb is independently hydrogen, —C1-4 alkyl, —C3-10 cycloalkyl, or -(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl or heterocyclyl group is optionally substituted by 1, 2 or 3 fluorine atoms;
• and
• R3 is selected from the group consisting of —C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C3-10 cycloalkyl, and -(5- to 10-membered)-C2-9 heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, —ORb, and —N(Rb)2, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl and -(5- to 10-membered)-C2-9 heterocyclyl, and wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl is optionally fused to a further (second) ring.

Use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, for the manufacture of a medicament for the treatment or prevention of a lysosomal storage disease, the compound of formula (I) having the structure:

• wherein
• A1, A2, and A3 are each independently selected from the group consisting of N, CH and C(R4), provided that at least one of A1, A2, or A3 is N;
• each R4 is independent selected from the group consisting of halogen, —C1-4 alkyl, —C1-4 alkoxy, and —CN;
• n is 1 or 2, wherein the alkylene chain can be optionally substituted with one or more —C1-4 alkyl groups;
• R1 is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, and —C(═O)Ra, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, optionally substituted —O—(C6-10 aryl);
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• and
• R2 is selected from the group consisting of hydrogen, —C1-4 alkyl, and —C3-6 cycloalkyl, wherein said —C1-4 alkyl is optionally substituted with —O(C1-4)alkyl optionally substituted with —O(C1-4)NH2, hydroxy, —CN, halogen, or —N(Rb)2;
• or
• R1 and R2 together with the nitrogen atom to which they are attached form an optionally substituted 5- to 10-membered heterocyclic ring, wherein said heterocyclic ring optionally contains 1, 2, or 3 additional heteroatoms selected from the group consisting of N, S, or O, and wherein said heterocyclic ring is optionally fused to a phenyl ring;
• Ra is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, and —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, and -(5- to 10-membered)-C2-9 heterocyclyl;
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• each Rb is independently hydrogen, —C1-4 alkyl, —C3-10 cycloalkyl, or -(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl or heterocyclyl group is optionally substituted by 1, 2 or 3 fluorine atoms;
• and
• R3 is selected from the group consisting of —C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C3-10 cycloalkyl, and -(5- to 10-membered)-C2-9 heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, —ORb, and —N(Rb)2, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl and -(5- to 10-membered)-C2-9 heterocyclyl, and wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl is optionally fused to a further (second) ring.

A pharmaceutical composition, comprising an effective amount of a compound of formula (I):

• or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient, for use in the treatment or prevention of a lysosomal storage disease, wherein
• A1, A2, and A3 are each independently selected from the group consisting of N, CH and C(R4), provided that at least one of A1, A2, or A3 is N;
• each R4 is independent selected from the group consisting of halogen, —C1-4 alkyl, —C1-4 alkoxy, and —CN;
• n is 1 or 2, wherein the alkylene chain can be optionally substituted with one or more —C1-4 alkyl groups;
• R1 is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, and —C(═O)Ra, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, optionally substituted —O—(C6-10 aryl);
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• and
• R2 is selected from the group consisting of hydrogen, —C1-4 alkyl, and —C3-6 cycloalkyl, wherein said —C1-4 alkyl is optionally substituted with —O(C1-4)alkyl optionally substituted with —O(C1-4)NH2, hydroxy, —CN, halogen, or —N(Rb)2;
• or
• R1 and R2 together with the nitrogen atom to which they are attached form an optionally substituted 5- to 10-membered heterocyclic ring, wherein said heterocyclic ring optionally contains 1, 2, or 3 additional heteroatoms selected from the group consisting of N, S, or O, and wherein said heterocyclic ring is optionally fused to a phenyl ring;
• Ra is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, and —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, and -(5- to 10-membered)-C2-9 heterocyclyl;
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• each Rb is independently hydrogen, —C1-4 alkyl, —C3-10 cycloalkyl, or -(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl or heterocyclyl group is optionally substituted by 1, 2 or 3 fluorine atoms;
• and
• R3 is selected from the group consisting of —C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C3-10 cycloalkyl, and -(5- to 10-membered)-C2-9 heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, —ORb, and —N(Rb)2, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl and -(5- to 10-membered)-C2-9 heterocyclyl, and wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl is optionally fused to a further (second) ring.

A method of treating or preventing a disease or disorder selected from the group consisting of Parkinson's disease, Lewy body disease, dementia, multiple system atrophy, epilepsy, bipolar disorder, schizophrenia, an anxiety disorder, major depression, polycyctic kidney disease, type 2 diabetes, open angle glaucoma, multiple sclerosis, and multiple myeloma, comprising administering to a patient in need thereof an effective amount of a compound of formula (I):

• or a pharmaceutically acceptable salt or solvate thereof, wherein
• A1, A2, and A3 are each independently selected from the group consisting of N, CH and C(R4), provided that at least one of A1, A2, or A3 is N;
• each R4 is independent selected from the group consisting of halogen, —C1-4 alkyl, —C1-4 alkoxy, and —CN;
• n is 1 or 2, wherein the alkylene chain can be optionally substituted with one or more —C1-4 alkyl groups;
• R1 is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, and —C(═O)Ra, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, optionally substituted —O—(C6-10 aryl);
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• and
• R2 is selected from the group consisting of hydrogen, —C1-4 alkyl, and C3-6 cycloalkyl, wherein said C1-4 alkyl is optionally substituted with —O(C1-4)alkyl optionally substituted with —O(C1-4)NH2, hydroxy, —CN, halogen, or —N(Rb)2;
• or
• R1 and R2 together with the nitrogen atom to which they are attached form an optionally substituted 5- to 10-membered heterocyclic ring, wherein said heterocyclic ring optionally contains 1, 2, or 3 additional heteroatoms selected from the group consisting of N, S, or O, and wherein said heterocyclic ring is optionally fused to a phenyl ring;
• Ra is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, and —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, and -(5- to 10-membered)-C2-9 heterocyclyl;
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• each Rb is independently hydrogen, —C1-4 alkyl, —C3-10 cycloalkyl, or -(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl or heterocyclyl group is optionally substituted by 1, 2 or 3 fluorine atoms;
• and
• R3 is selected from the group consisting of —C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C3-10 cycloalkyl, and -(5- to 10-membered)-C2-9 heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, —ORb, and —N(Rb)2, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl and -(5- to 10-membered)-C2-9 heterocyclyl, and wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl is optionally fused to a further (second) ring.

A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment or prevention of a disease or disorder selected from the group consisting of Parkinson's disease, Lewy body disease, dementia, multiple system atrophy, epilepsy, bipolar disorder, schizophrenia, an anxiety disorder, major depression, polycyctic kidney disease, type 2 diabetes, open angle glaucoma, multiple sclerosis, and multiple myeloma, the compound of formula (I) having the structure:

• wherein
• A1, A2, and A3 are each independently selected from the group consisting of N, CH and C(R4), provided that at least one of A1, A2, or A3 is N;
• each R4 is independently selected from the group consisting of halogen, —C1-4 alkyl, —C1-4 alkoxy, and —CN;
• n is 1 or 2, wherein the alkylene chain can be optionally substituted with one or more —C1-4 alkyl groups;
• R1 is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, and —C(═O)Ra, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, optionally substituted —O—(C6-10 aryl);
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• and
• R2 is selected from the group consisting of hydrogen, —C1-4 alkyl, and —C3-6 cycloalkyl, wherein said —C1-4 alkyl is optionally substituted with —O(C1-4)alkyl optionally substituted with —O(C1-4)NH2, hydroxy, —CN, halogen, or —N(Rb)2;
• or
• R1 and R2 together with the nitrogen atom to which they are attached form an optionally substituted 5- to 10-membered heterocyclic ring, wherein said heterocyclic ring optionally contains 1, 2, or 3 additional heteroatoms selected from the group consisting of N, S, or O, and wherein said heterocyclic ring is optionally fused to a phenyl ring;
• Ra is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, and —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, and -(5- to 10-membered)-C2-9 heterocyclyl;
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• each Rb is independently hydrogen, —C1-4 alkyl, —C3-10 cycloalkyl, or -(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl or heterocyclyl group is optionally substituted by 1, 2 or 3 fluorine atoms;
• and
• R3 is selected from the group consisting of —C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C3-10 cycloalkyl, and -(5- to 10-membered)-C2-9 heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, —ORb, and —N(Rb)2, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl and -(5- to 10-membered)-C2-9 heterocyclyl, and wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl is optionally fused to a further (second) ring.

Use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, for the manufacture of a medicament for the treatment or prevention of a disease or disorder selected from the group consisting of Parkinson's disease, Lewy body disease, dementia, multiple system atrophy, epilepsy, bipolar disorder, schizophrenia, an anxiety disorder, major depression, polycyctic kidney disease, type 2 diabetes, open angle glaucoma, multiple sclerosis, and multiple myeloma, the compound of formula (I) having the structure:

• wherein
• A1, A2, and A3 are each independently selected from the group consisting of N, CH and C(R4), provided that at least one of A1, A2, or A3 is N;
• each R4 is independent selected from the group consisting of halogen, —C1-4 alkyl, —C1-4 alkoxy, and —CN;
• n is 1 or 2, wherein the alkylene chain can be optionally substituted with one or more —C1-4 alkyl groups;
• R1 is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, and —C(═O)Ra, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, optionally substituted —O—(C6-10 aryl);
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• and
• R2 is selected from the group consisting of hydrogen, —C1-4 alkyl, and —C3-6 cycloalkyl, wherein said —C1-4 alkyl is optionally substituted with —O(C1-4)alkyl optionally substituted with —O(C1-4)NH2, hydroxy, —CN, halogen, or —N(Rb)2;
• or
• R1 and R2 together with the nitrogen atom to which they are attached form an optionally substituted 5- to 10-membered heterocyclic ring, wherein said heterocyclic ring optionally contains 1, 2, or 3 additional heteroatoms selected from the group consisting of N, S, or O, and wherein said heterocyclic ring is optionally fused to a phenyl ring;
• Ra is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, and —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, and -(5- to 10-membered)-C2-9 heterocyclyl;
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• each Rb is independently hydrogen, —C1-4 alkyl, —C3-10 cycloalkyl, or -(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl or heterocyclyl group is optionally substituted by 1, 2 or 3 fluorine atoms;
• and
• R3 is selected from the group consisting of —C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C3-10 cycloalkyl, and -(5- to 10-membered)-C2-9 heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, —ORb, and —N(Rb)2, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl and -(5- to 10-membered)-C2-9 heterocyclyl, and wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl is optionally fused to a further (second) ring.

A pharmaceutical composition, comprising an effective amount of a compound of formula (I):

• or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient, for use in the treatment or prevention of a disease or disorder selected from the group consisting of Parkinson's disease, Lewy body disease, dementia, multiple system atrophy, epilepsy, bipolar disorder, schizophrenia, an anxiety disorder, major depression, polycyctic kidney disease, type 2 diabetes, open angle glaucoma, multiple sclerosis, and multiple myeloma, wherein
• A1, A2, and A3 are each independently selected from the group consisting of N, CH and C(R4), provided that at least one of A1, A2, or A3 is N;
• each R4 is independent selected from the group consisting of halogen, —C1-4 alkyl, —C1-4 alkoxy, and —CN;
• n is 1 or 2, wherein the alkylene chain can be optionally substituted with one or more —C1-4 alkyl groups;
• R1 is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, and —C(═O)Ra, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, optionally substituted —O—(C6-10 aryl);
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• and
• R2 is selected from the group consisting of hydrogen, —C1-4 alkyl, and —C3-6 cycloalkyl, wherein said —C1-4 alkyl is optionally substituted with —O(C1-4)alkyl optionally substituted with —O(C1-4)NH2, hydroxy, —CN, halogen, or —N(Rb)2;
• or
• R1 and R2 together with the nitrogen atom to which they are attached form an optionally substituted 5- to 10-membered heterocyclic ring, wherein said heterocyclic ring optionally contains 1, 2, or 3 additional heteroatoms selected from the group consisting of N, S, or O, and wherein said heterocyclic ring is optionally fused to a phenyl ring;
• Ra is selected from the group consisting of —C1-4 alkyl, —C3-10 cycloalkyl, —C1-4 alkyl-C3-10 cycloalkyl, —C6-10 aryl, —C1-4 alkyl-C6-10 aryl, (5- to 10-membered)-C1-9 heteroaryl, —C1-4 alkyl-(5- to 10-membered)-C1-9 heteroaryl, -(5- to 10-membered)-C2-9 heterocyclyl, and —C1-4 alkyl-(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, —CN, —ORb, —SRb, —N(Rb)2, —C1-4 alkyl optionally substituted with 1, 2, or 3 halogen atoms, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl, and -(5- to 10-membered)-C2-9 heterocyclyl;
• and wherein said cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heteroaryl, alkylheteroaryl, heterocyclyl and alkylheterocyclyl is optionally fused to a further (second) ring;
• each Rb is independently hydrogen, —C1-4 alkyl, —C3-10 cycloalkyl, or -(5- to 10-membered)-C2-9 heterocyclyl, wherein said alkyl, cycloalkyl or heterocyclyl group is optionally substituted by 1, 2 or 3 fluorine atoms;
• and
• R3 is selected from the group consisting of —C6-10 aryl, -(5- to 10-membered)-C1-9 heteroaryl, —C3-10 cycloalkyl, and -(5- to 10-membered)-C2-9 heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl groups are optionally substituted with 1, 2 or 3 substituents each independently selected from the group consisting of halogen, hydroxy, CN, —ORb, —SRb, —N(Rb)2, —C1-4alkyl optionally substituted with 1, 2, or 3 substituents each independently selected from the group consisting of halogen, —CN, —ORb, and —N(Rb)2, optionally substituted —C6-10 aryl, optionally substituted -(5- to 10-membered)-C1-9 heteroaryl and -(5- to 10-membered)-C2-9 heterocyclyl, and wherein said aryl, heteroaryl, cycloalkyl, and heterocyclyl is optionally fused to a further (second) ring.