	US 12,264,156 B2
	Compounds and pharmaceutical compositions thereof for the treatment of diseases
David Amantini, Romainville (FR); Reginald Christophe Xavier Brys, Mechelen (BE); Denis Bucher, Rheinfelden (CH); Steve Irma Joel De Vos, Mechelen (BE); Nicolas Desroy, Romainville (FR); Agnès Marie Joncour, Romainville (FR); Christophe Peixoto, Romainville (FR); Taoues Temal-Laïb, Romainville (FR); and Amynata Tirera, Romainville (FR)
Assigned to GALAPAGOS NV, Mechelen (BE)
Appl. No. 17/252,146
Filed by GALAPAGOS NV, Mechelen (BE)
PCT Filed May 29, 2019, PCT No. PCT/EP2019/063956 § 371(c)(1), (2) Date Dec. 14, 2020, PCT Pub. No. WO2019/238424, PCT Pub. Date Dec. 19, 2019.
Claims priority of application No. 1809836 (GB), filed on Jun. 15, 2018; and application No. 1817344 (GB), filed on Oct. 25, 2018.
Prior Publication US 2022/0402911 A1, Dec. 22, 2022
Int. Cl. C07D 471/04 (2006.01); A61P 1/00 (2006.01); A61P 17/06 (2006.01); A61P 19/02 (2006.01)

CPC C07D 471/04 (2013.01) [A61P 1/00 (2018.01); A61P 17/06 (2018.01); A61P 19/02 (2018.01)]

20 Claims

1. A compound according to Formula I:

wherein,

X is N or CH;

Y is N or CR²b;

Z is

—NHR^3a,

N-linked 4-7 membered heterocycloalkyl further having zero, one, or two additional heteroatoms independently selected from N, O, and S, optionally substituted with one or more independently selected R¹⁵groups, or

—NR^3b—, wherein the N atom and R^2atogether with the atoms onto which they are attached form a fused 5-6 membered heterocycloalkenyl comprising one or two double bonds;

R¹is

C_1-8alkyl optionally substituted with one or more independently selected R⁴groups,

phenyl,

C_3-8monocyclic or bridged polycyclic cycloalkyl optionally substituted with one or more independently selected R⁵groups,

4-8 membered monocyclic, spirocyclic, or bridged polycyclic heterocycloalkyl having one, two, or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more independently selected C_1-4alkyl optionally substituted with one or more independently selected —CN or C(═O)—C_1-4alkoxy, or

5-6 membered monocyclic heteroaryl having one, two, or three heteroatoms independently selected from N, O, and S;

R^2aand R^2bare independently selected from

halo,

C_1-4alkyl,

C_1-4alkoxy optionally substituted with one or more independently selected halo or C_1-4alkoxy, and

NR^6aR^6b;

R^3ais

C_1-6alkyl optionally substituted with one or more independently selected halo or —CN, or

C_3-7cycloalkyl optionally substituted with one or more independently selected halo or —OH;

R^3bis selected from H, C_3-7cycloalkyl and C_1-6alkyl optionally substituted with one or more independently selected halo or —CN;

each R⁴is independently selected from

halo,

—OH,

—CN,

phenyl,

—C(═O)OH,

—O—C(═O)—C_1-4alkyl,

—O—S(═O)₂—C_1-4alkyl,

C_1-4alkoxy optionally substituted with one or more independently selected

—OH

C_1-4alkoxy,

4-8 membered monocyclic heterocycloalkyl having one, two, or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more independently selected C_1-4alkyl, or

NR^7aR^7b, wherein each R^7aand R^7bis independently selected from H and C_1-4alkyl,

C_3-7cycloalkyl optionally substituted with one or more independently selected halo, —C(═O)—C_1-4alkoxy, —NR^8aR^8b, or C_1-4alkyl optionally substituted with one or more independently selected —NR^9aR^9b,

5-6 membered monocyclic heterocycloalkyl comprising one or two N atoms fused to a 5-6 membered monocyclic heteroaryl having one, two, or three heteroatoms independently selected from N, O, and S, which heteroaryl is optionally substituted with one or more independently selected C_1-4alkyl,

5-6 membered monocyclic heteroaryl having one, two, or three heteroatoms independently selected from N, O, and S, which heteroaryl is optionally substituted with one or more independently selected C_1-4alkyl or C_3-7cycloalkyl,

4-1l membered monocyclic, spirocyclic, or bridged polycyclic heterocycloalkyl having one, two, or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more independently selected R¹⁰,

—NR^11aR^11b,

—C(═O)—C_1-4alkoxy, and

—C(═O)—NR^12aR^12b;

each R is selected from

halo,

—CN, and

—N^13aR^13b;

each R^6aand R^5bis independently selected from H and C_1-4alkyl;

each R¹⁰is selected from

—OH,

phenyl,

═NH,

halo,

oxo,

—CN,

—C(═O)H,

C(═O)NH₂,

—C(═O)OH,

NR^14aR^14b,

C_1-4alkyl optionally substituted with one or more independently selected halo, —CN, —OH, —C(═O)—C_1-4alkoxy, or C_1-4alkoxy,

C_3-7cycloalkyl,

4-6 membered monocyclic heterocycloalkyl having one, two, or three heteroatoms independently selected from N, O, and S,

—C(═O)—C_1-4alkyl,

—S(═O)₂—C_1-4alkyl, and

—C(═O)—C_1-6alkoxy;

each R^11a, R^11bis independently selected from

—H,

phenyl,

C_1-4alkyl optionally substituted with one or more independently selected halo, —OH, —CN, or C_1-4alkoxy,

C_3-7cycloalkyl,

—C(═O)—C_1-4alkoxy,

—C(═O)—C_1-4alkyl optionally substituted with one or more independently selected halo, and

5-6 membered monocyclic heteroaryl having one, two, or three heteroatoms independently selected from N, O, and S;

each R^8a, R^8b, R^9a, R^9b, R^12a, R^12bR^13a, and R^13bis independently selected from H and C_1-4alkyl;

each R^14aand R^14bis independently selected from 1, C_1-4alkyl, and —S(═O)₂—C_1-4alkyl; and

each R¹⁵is independently selected from —OH, —CN, and C_1-4alkyl optionally substituted with one or more independently selected halo or —CN.