5-[(piperazin-1-yl)-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as adamts inhibitors for the treatment of osteoarthritis

A compound according to Formula I:

• wherein
• R1 is:
• H,
• C1-4 alkyl optionally substituted with one or more independently selected R4 groups,
• C3-7 monocyclic cycloalkyl optionally substituted with one or more independently selected R4 groups,
• 4-7 membered monocyclic heterocycloalkyl comprising 1 to 2 heteroatoms independently selected from N, O, or S, optionally substituted with one or more independently selected C1-4 alkyl, —C(═O)C1-4 alkyl, or —C(═O)OC1-4 alkyl,
• phenyl optionally substituted with one or more independently selected R5 groups,
• phenyl fused to a 5-6 membered monocyclic heterocycloalkyl comprising 1, 2 or 3 heteroatoms independently selected from N, O, or S, which heterocycloalkyl is optionally substituted with one or more ═O,
• 5-6 membered monocyclic heteroaryl comprising 1 or 2 heteroatoms independently selected from N, O, or S, optionally substituted with one or more independently selected R5 groups;
• R2 is independently selected from:
• H,
• OH,
• C1-4 alkoxy, or
• C1-4 alkyl optionally substituted with one
• OH,
• —CN,
• C1-4 alkoxy optionally substituted with one phenyl, or
• 5-6 membered monocyclic heteroaryl comprising 1 or 2 heteroatoms independently selected from N, O, or S, optionally substituted with one or more independently selected C1-4 alkyl;
• each R3a, and R3b is independently selected from:
• H, or
• C1-4 alkyl;
• Cy is
• 6-10 membered monocyclic or fused bicyclic aryl optionally substituted with one or more independently selected R6 groups,
• 5-10 membered monocyclic or fused bicyclic heteroaryl comprising 1, 2 or 3 heteroatoms independently selected from N, O, or S, optionally substituted with one or more independently selected R6 groups;
• R4 is
• halo,
• OH,
• —CN,
• C1-4 alkyl,
• C1-4 alkoxy optionally substituted with C1-4 alkoxy, or phenyl,
• C1-4 thioalkoxy,
• 4-7-membered monocyclic heterocycloalkyl comprising one or more heteroatoms independently selected from N, S, or O, optionally substituted with one or more halo, or
• —C(═O)OC1-4 alkyl,
• phenyl,
• —S(═O)2C1-4 alkyl
• —C(═O)OR7a
• —C(═O)NR7bR7c
• —NHC(═O)OR7d
• —NHC(═O)R7e, or
• —NR8aR8b;
• each R5 is
• halo,
• OH,
• —CN,
• C1-4 alkyl optionally substituted with one or more independently selected halo, —NR9aR9b, or —C(═O)NR9cR9y,
• C1-4 alkoxy optionally substituted with —NR9eR9f, or
• —S(═O)2C1-4 alkyl;
• each R6 is
• halo,
• —CN,
• —NO2,
• —CH3,
• 5-10 membered monocyclic or fused bicyclic heteroaryl comprising 1, 2 or 3 heteroatoms independently selected from N, O, or S, optionally substituted with one or more independently selected halo, C1-4 alkyl, or C1-4 alkoxy, or
• —NR9gR9h;
• each R7a, R7b, R7c, R7d, or R7e, is
• H, or
• C1-4 alkyl optionally substituted with OH, or C1-4 alkoxy;
• each R8a, or R8b is independently selected from
• H, or
• C1-4 alkyl optionally substituted with OH, C1-4 alkoxy, or phenyl;
• each R9a, R9b, R9c, R9d, R9e, R9f, R9g, and R9h is independently selected from H, or C1-4 alkyl;
• or a pharmaceutically acceptable salt, or a solvate, or a pharmaceutically acceptable salt of a solvate thereof;
• or a biologically active metabolite thereof;
• provided that:
• R1 and R2 are not simultaneously H, and
• when R1 is Me, and R2 is H, then Cy is not
• or a pharmaceutically acceptable salt, or a solvate, or the salt of the solvate thereof.