5-[3-[piperazin-1-yl]-3-oxo-propyl]-imidazolidine-2,4-dione derivatives as adamts 4 and 5 inhibitors for treating e.g. 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, and 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, and 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, and S, optionally substituted with one or more independently selected R5 groups;
• R2 is independently selected from:
• H,
• —OH,
• C1-4 alkoxy, and
• C1-4 alkyl optionally substituted with one
• OH,
• —CN,
• C1-4 alkoxy optionally substituted with one phenyl, and
• 5-6 membered monocyclic heteroaryl comprising 1 or 2 heteroatoms independently selected from N, O, and S, optionally substituted with one or more independently selected C1-4 alkyl;
• each R3a, and R3b is independently selected from H, and C1-4 alkyl optionally substituted with one or more halo;
• Cy is
• 6-10 membered monocyclic or fused bicyclic aryl,
• 5-10 membered monocyclic or fused bicyclic heteroaryl comprising 1, 2 or 3 heteroatoms independently selected from N, O, and S;
• R4 is
• halo,
• OH,
• —CN,
• C1-4 alkyl,
• C1-4 alkoxy optionally substituted with one C1-4 alkoxy, or phenyl,
• C1-4 thioalkoxy,
• 4-7-membered monocyclic heterocycloalkyl comprising one or more heteroatoms independently selected from N, S, and 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
• —NR8aR8b;
• each R5 is
• halo,
• OH,
• —CN,
• C1-4 alkyl optionally substituted with one or more independently selected halo, —NR9aR9b, or —C(═O)NR9cR9d,
• C1-4 alkoxy optionally substituted with —NR9eR9f, or
• —S(═O)2C1-4 alkyl;
• each R6a is
• C2-4 alkyl optionally substituted with one or more halo,
• C1-4 alkoxy optionally substituted with one or more halo,
• the subscript n is 0, 1, 2 or 3
• each R6b is independently selected from
• halo,
• —CN,
• —NO2,
• —C1-4 alkyl,
• —C1-4 alkoxy
• 5-10 membered monocyclic or fused bicyclic heteroaryl comprising 1, 2 or 3 heteroatoms independently selected from N, O, and S, optionally substituted with one or more independently selected halo, C1-4 alkyl, or C1-4 alkoxy, and
• —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, and C1-4 alkyl optionally substituted with OH, C1-4 alkoxy, or phenyl;
• each R9a, R9b, R9c, R9d, R9e, R9f, R9g, R9h is independently selected from H, and
• 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 when R1, R2, R3a and R3b are H, Cy is phenyl and R6a is —OCH3, then the subscript n is not 0, and the compound is not (5R)-5-[3-[(3S)-4-(4-chloro-3-methoxy-5-methyl-phenyl)-3-methyl-piperazin-1-yl]-3-oxo-propyl]-5-methyl-imidazolidine-2,4-dione.