Granted Patent B2

US 12,606,554 · App. 17/614,814 · Granted Apr 21, 2026

Inventor: Taoues Temal-Laïb (Romainville, FR)

Assignee: ONCO3R Therapeutics BV

C07D471/04A61P1/04A61P11/00A61P19/02C07D487/04

Abstract

Claims (96)

1 . A compound according to Formula I:

wherein,

W is N or CH;

one of X 1 and X 2 is N and the other one is C, with the proviso that when W is CH, X 2 is not N;

Y is N or CR 2b ;

Z is

—NHR 3a ,

N-linked 4-7 membered heterocycloalkyl with zero, one, or two additional heteroatoms independently selected from N, O, and S, optionally substituted with one or more independently selected R 15 groups, or

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

R 1 is

C 1-8 alkyl optionally substituted with one or more independently selected R 4 groups,

phenyl,

C 3-8 monocyclic or bridged polycyclic cycloalkyl optionally substituted with one or more independently selected R 5 groups,

4-8 membered monocyclic, spirocyclic, or bridged polycyclic heterocycloalkyl with one, two, or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more independently selected C 1-4 alkyl optionally substituted with one or more independently selected —CN or —C(═O)—C 1-4 alkoxy, or

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

R 2a and R 2b are independently selected from

halo,

C 1-4 alkyl,

C 1-4 alkoxy optionally substituted with one or more independently selected halo or C 1-4 alkoxy, and

—NR 6a R 6b ;

R 3a is

C 1-6 alkyl optionally substituted with one or more independently selected halo or —CN, or

C 3-7 cycloalkyl optionally substituted with one or more independently selected halo or —OH;

R 3b is selected from H, C 3-7 cycloalkyl and C 1-6 alkyl optionally substituted with one or more independently selected halo or —CN;

each R 4 is independently selected from

halo,

—OH,

—CN,

phenyl,

—C(═O) OH,

—O—C(═O)—C 1-4 alkyl,

—O—S(═O) 2 -C 1-4 alkyl,

C 1-4 alkoxy optionally substituted with one or more independently selected

—OH,

C 1-4 alkoxy,

4-8 membered monocyclic heterocycloalkyl with one, two, or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more independently selected C 1-4 alkyl, or

—NR 7a R 7b , wherein each R 7a and R 7b is independently selected from H and C 1-4 alkyl,

C 3-7 cycloalkyl optionally substituted with one or more independently selected halo, —C(═O)—C 1-4 alkoxy, —NR 8a R 8b , or C 1-4 alkyl optionally substituted with one or more independently selected —NR 9a R 9b ,

5-6 membered monocyclic heterocycloalkyl with one or two N atoms fused to a 5-6 membered monocyclic heteroaryl with one, two, or three heteroatoms independently selected from N, O, and S, which heteroaryl is optionally substituted with one or more independently selected C 1-4 alkyl,

5-6 membered monocyclic heteroaryl with one, two, or three heteroatoms independently selected from N, O, and S, which heteroaryl is optionally substituted with one or more independently selected C 1-4 alkyl or C 3-7 cycloalkyl,

4-11 membered monocyclic, spirocyclic, or bridged polycyclic heterocycloalkyl with one, two, or three heteroatoms independently selected from N, O, and S, which heterocycloalkyl is optionally substituted with one or more independently selected R 10 ,

—NR 11a R 11b ,

—C(═O)—C 1-4 alkoxy, and

—C(═O)—NR 12a R 12b ;

each R 5 is selected from

halo,

—CN, and

—NR 13a R 13b :

each R 6a and R 6b is independently selected from H and C 1-4 alkyl;

each R 10 is selected from

—OH,

phenyl,

═NH,

halo,

oxo,

—CN,

—C(═O) H,

—C(═O)NH 2 ,

—C(═O) OH,

—NR 14a R 14b ,

C 1-4 alkyl optionally substituted with one or more independently selected halo, —CN, —OH, —C(═O)—C 1-4 alkoxy, or C 1-4 alkoxy,

C 3-7 cycloalkyl,

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

—C(═O)C 1-4 alkyl,

—S(═O) 2 -C 1-4 alkyl, and

—C(═O)—C 1-6 alkoxy;

each R 11a , R 11b is independently selected from

H,

phenyl,

C 1-4 alkyl optionally substituted with one or more independently selected halo, —OH, —CN, or C 1-4 alkoxy,

C 3-7 cycloalkyl,

—C(═O)—C 1-4 alkoxy,

—C(═O)—C 1-4 alkyl optionally substituted with one or more independently selected halo, and

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

each R 8a , R 8b , R 9a , R 9b , R 12a , R 12b , R 13a and R 13b is independently selected from H and C 1-4 alkyl;

each R 14a and R 14b is independently selected from H, C 1-4 alkyl, and —S(═O) 2 -C 1-4 alkyl; and

each R 15 is independently selected from —OH, —CN, and C 1-4 alkyl optionally substituted with one or more independently selected halo or —CN,

or a pharmaceutically acceptable salt thereof.

2 . A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein Y is CR 2b and R 2b is C 1-4 alkoxy.

3 . A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 2a is —O—CH 3 , substituted with one, two, or three independently selected halo.

4 . A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein Z is —NR 3b , wherein the N atom and R 2a together with the atoms onto which they are attached form a fused 1,2,3,6-tetrahydropyridine.

5 . A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein the compound is according to any one of Formulae IIIa-IIIh:

6 . A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 1 is —CH 3 or —CH 2 CH 3 , each of which is substituted with one R 4 group.

7 . A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein the compound is according to any one of Formulae IVa-IVp:

8 . A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 4 is —NH—CH 3 , —N(CH 3 ) 2 , —NH—CH 2 CH 3 , —N(CH 2 CH 3 ) 2 , —N(CH(CH 3 ) 2 ) 2 , or —N(CH 3 )—CH 2 CHF 2 .

9 . A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 4 is azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, tetrahydropyranyl, morpholinyl, dioxanyl, 2-oxa-5-azabicyclo[2.2.1]heptanyl, 3-oxa-8-azabicyclo[3.2.1]octanyl, or 8-oxa-3-azabicyclo[3.2.1]octanyl.

10 . A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 4 is morpholinyl.

11 . A compound or pharmaceutically acceptable salt thereof, according to claim 1 , wherein R 4 is dioxanyl.

12 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of a compound or pharmaceutically acceptable salt thereof according to claim 1 .

13 . A method for treatment of inflammatory bowel disease, psoriasis, systemic lupus erythematosus, atopic dermatitis, fibrosis, or osteoarthritis, comprising administering a compound or pharmaceutically acceptable salt thereof, according to claim 1 , to a human in need thereof.

14 . The method of claim 13 , wherein the method is for treatment of inflammatory bowel disease.

15 . The method of claim 13 , wherein the method is for treatment of psoriasis.

16 . The method of claim 13 , wherein the method is for treatment of systemic lupus erythematosus.

17 . The method of claim 13 , wherein the method is for treatment of atopic dermatitis.

18 . The method of claim 13 , wherein the method is for treatment of fibrosis.

19 . The method of claim 13 , wherein the method is for treatment of osteoarthritis.

Assignments (7)

Priority Claims (1)

Continuity (1)

References Cited (53)