US 12,391,679 B2
Benzamide-substituted bicyclic imidazo- and pyrazolo-fused -pyridine, -pyrimide, and -pyridazine compounds for treatment of inflammatory diseases
Luke Jonathan Alvey, Romainville (FR); Denis Bucher, Rheinfelden (CH); Nicolas Desroy, Romainville (FR); Hélène Marie Jary, Romainville (FR); Christophe Peixoto, Romainville (FR); Taoues Temal-Laïb, Romainville (FR); Amynata Tirera, Romainville (FR); Florence Marie-Emilie Bonnaterre, Romainville (FR); and Béranger Duthion, Romainville (FR)
Assigned to ONCO3R Therapeutics BV, Brussels (BE)
Appl. No. 17/614,854
Filed by ONCO3R Therapeutics BV, Brussels (BE)
PCT Filed May 25, 2020, PCT No. PCT/EP2020/064368
§ 371(c)(1), (2) Date Nov. 29, 2021,
PCT Pub. No. WO2020/239658, PCT Pub. Date Dec. 3, 2020.
Claims priority of application No. 1907616 (GB), filed on May 29, 2019.
Prior Publication US 2022/0340548 A1, Oct. 27, 2022
Int. Cl. C07D 405/10 (2006.01); A61P 1/00 (2006.01); A61P 9/00 (2006.01); A61P 11/00 (2006.01); A61P 19/02 (2006.01); A61P 37/00 (2006.01); C07D 235/16 (2006.01); C07D 401/10 (2006.01); C07D 471/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 405/10 (2013.01) [A61P 1/00 (2018.01); A61P 9/00 (2018.01); A61P 11/00 (2018.01); A61P 19/02 (2018.01); A61P 37/00 (2018.01); C07D 235/16 (2013.01); C07D 401/10 (2013.01); C07D 471/04 (2013.01); C07D 519/00 (2013.01)] 15 Claims
 
1. A compound according to Formula I:

OG Complex Work Unit Chemistry
wherein,
W1 is N or CR3 and W2 is N or CH, with the proviso that W1 and W2 cannot both be N;
one of X1, X2 and X3 is N and the other two are C;
Y is N or CR2b;
Z is
—NR4aR4b,
—R4c—, wherein the N atom and R2a together with the atoms onto which they are attached form a fused 5-6 membered heterocycloalkenyl comprising one double bond, or
N-linked 4-7 membered monocyclic or spirocyclic heterocycloalkyl further comprising zero, one, or two additional heteroatoms independently selected from N, O, and S, optionally substituted with one or more independently selected R5 groups;
R1a is selected from
H,
halo,
—OH,
—CN,
C1-6 alkyl optionally substituted with one or more independently selected R6,
C1-4 alkoxy optionally substituted with one or more —OH or 5-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S,
—C(O)—R7,
—NR8aR8b,
—S(═O)2—C1-4 alkyl,
5-6 membered monocyclic heteroaryl comprising one, two or three heteroatoms independently selected from N, O, and S, which heteroaryl is optionally substituted with one or more independently selected C1-4 alkyl, and
4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S;
R1b and R1c are independently selected from
halo,
—OH,
—CN,
C1-4 alkyl optionally substituted with one or more independently selected —OH, —CN, or C2-4 alkenyl,
C3-7 cycloalkyl,
4-8 membered monocyclic or spirocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more independently selected R9 groups, and
—NR10aR10b,
or R1b and R1c together with the atom onto which they are attached form a C3-6 cycloalkyl,
or R1b and R1c together with the atom onto which they are attached form a 4-6 membered monocyclic heterocycloalkyl comprising one, two, or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more independently selected R11 groups;
R2a and R2b are independently selected from
halo,
C1-4 alkyl,
C1-4 alkoxy optionally substituted with one or more independently selected halo, —OH, or C1-4 alkoxy,
—NR12aR12b, and
—OH;
R3 is H, halo, or C1-4 alkoxy optionally substituted with one or more independently selected —OH or C1-4 alkoxy;
R4a is H or C1-4 alkyl;
R4b is selected from
C1-6 alkyl optionally substituted with one or more independently selected R13,
C3-7 cycloalkyl optionally substituted with one or more independently selected R14a,
4-7 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more independently selected R14b, and
5-6 membered monocyclic heteroaryl comprising one, two or three heteroatoms independently selected from N, O, and S, which heteroaryl is optionally substituted with one or more independently selected C1-4 alkyl;
R4c is H, C3-7 cycloalkyl, or C1-6 alkyl optionally substituted with one or more independently selected halo or —CN;
each R5 is independently selected from
oxo,
halo,
—CN,
—OH,
—NR15aR15b,
phenyl,
C3-7 cycloalkyl,
C2-4 alkynyl,
—C(═O)—C1-4 alkoxy,
C1-4 alkoxy optionally substituted with one or more independently selected halo or phenyl,
C1-4 alkyl optionally substituted with one or more independently selected halo, —OH, or C1-4 alkoxy, and
4-7 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S;
each R6 is independently selected from
halo,
—O—R16,
—NR17aR17b,
5-6 membered monocyclic heteroaryl comprising one, two or three heteroatoms independently selected from N, O, and S, and
4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more independently selected halo;
R7 is —OH, C1-4 alkyl, C1-4 alkoxy, —NR18aR18b, or 4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more —OH;
R8a and R8b are independently H, —C(═O)—C1-4 alkoxy, or C1-4 alkyl optionally substituted with one or more independently selected halo, —CN or —OH;
each R9 is independently halo, —OH, or C1-4 alkyl optionally substituted with one or more —OH;
each R10a and R10b is independently H or C1-4 alkyl optionally substituted with one or more —OH;
each R11 is independently selected from
C1-4 alkyl optionally substituted with one or more independently selected-CN or C1-4 alkoxy,
—C(═O)—C1-6 alkyl, and
—C(═O)—C1-6 alkoxy;
each R12a and R12b is independently H or C1-4 alkyl optionally substituted with one —OH or C1-4 alkoxy;
each R13 is independently selected from
halo,
—CN,
—NR19aR19b,
—OH,
C1-4 alkoxy,
C3-7 cycloalkyl,
—S(═O)2—C1-4 alkyl,
4-7 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S, and
5-6 membered monocyclic heteroaryl comprising one, two or three heteroatoms independently selected from N, O, and S, which heteroaryl is optionally substituted with one or more independently selected C1-4 alkyl;
each R14a and R14b is independently selected from
halo,
oxo,
C1-4 alkyl optionally substituted with one or more independently selected halo, —OH, or C1-4 alkoxy,
—OH,
C1-4 alkoxy, and
—NR20aR20b;
each R15a and R15b is independently H, C1-4 alkyl, or —C(═O)—C1-4 alkoxy;
each R16 is independently selected from
H,
—S(═O)2—C1-4 alkyl,
C1-4 alkyl optionally substituted with one or more —C(═O)—NR21aR21b or 4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S, and
4-6 membered monocyclic heterocycloalkyl comprising one, two or three heteroatoms independently selected from N, O, and S;
each R17a and R17b is independently H or C1-4 alkyl optionally substituted with one or more independently selected-OH or C1-4 alkoxy;
R18a and R18b are independently H or C1-4 alkyl optionally substituted with one or more independently selected —OH or C1-4 alkoxy;
each R19a, R19b, R20a, R20b, R21a, and R21b is independently H or C1-4 alkyl;
or a pharmaceutically acceptable salt thereof.