US 12,240,812 B2
Compound for inhibiting PGE2/EP4 signaling transduction inhibiting, preparation method therefor, and medical uses thereof
Yongqi Deng, Hong Kong (CN); and Jian Sun, Hong Kong (CN)
Assigned to Keythera (Suzhou) Pharmaceuticals Co. Ltd., Jiangsu (CN)
Appl. No. 17/423,248
Filed by Keythera (Suzhou) Pharmaceuticals Co. Ltd., Jiangsu (CN)
PCT Filed Jan. 16, 2020, PCT No. PCT/CN2020/072487
§ 371(c)(1), (2) Date Jul. 15, 2021,
PCT Pub. No. WO2020/151566, PCT Pub. Date Jul. 30, 2020.
Claims priority of application No. 201910057555.2 (CN), filed on Jan. 22, 2019.
Prior Publication US 2022/0064113 A1, Mar. 3, 2022
Int. Cl. C07D 209/10 (2006.01); A61K 45/06 (2006.01); A61P 35/00 (2006.01); C07D 401/06 (2006.01); C07D 401/14 (2006.01); C07D 405/06 (2006.01); C07D 413/06 (2006.01); C07D 417/06 (2006.01); C07D 471/04 (2006.01)
CPC C07D 209/10 (2013.01) [A61K 45/06 (2013.01); A61P 35/00 (2018.01); C07D 401/06 (2013.01); C07D 401/14 (2013.01); C07D 405/06 (2013.01); C07D 413/06 (2013.01); C07D 417/06 (2013.01); C07D 471/04 (2013.01)] 12 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Chemistry
or a tautomer, mesomer, racemate, enantiomer, diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof,
wherein:
M1, M2, M3, M5, and M6 are a C—R4;
M4 is a C atom;
M7 is an N-atom:
ring A is selected from the group consisting of C6-10 aryl, C3-6 cycloalkyl, 5 to 10 membered heteroaryl and 3 to 6 membered heterocyclyl;

OG Complex Work Unit Chemistry
Y is selected from the group consisting of a bond, C1-4 alkylene, —CR5R6—, —O—, —OC1-4 alkylene-, —NR9C1-4 alkylene- and —NR9—, wherein the C1-4 alkylene is optionally substituted by one or more substituents selected from the group consisting of H atom, D atom, halogen, hydroxy, cyano, amino, nitro, C1-4 alkyl, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy, hydroxyC1-4 alkyl, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl;
R1 and R2 are identical or different and are each independently selected from the group consisting of H atom, D atom, cyano, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, —C(O)OR4, C(O)NR7R8, —COR4, —S(O)mR4, —NR7R8, C6-10 aryl and 5 to 10 membered heteroaryl, wherein the C1-4 alkyl and C1-4 alkoxy are each independently optionally substituted by one or more substituents selected from the group consisting of H atom, D atom, halogen, hydroxy, cyano, amino, nitro, C1-4 alkyl, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy, hydroxyC1-4 alkyl, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, —C(O)OR4, C(O)NR7R8, —COR4, —NR4C(O)NR7R8, —OC(O)NR7R8, —NR7C(O)OR4, —S(O)mR4, —NR7R8, C6-10 aryl and 5 to 10 membered heteroaryl; or, R1 and R2 together with the atom to which they are attached form a C3-6 cycloalkyl or 3 to 6 membered heterocyclyl, wherein the C3-6 cycloalkyl and 3 to 6 membered heterocyclyl are each independently optionally substituted by one or more substituents selected from the group consisting of D atom, halogen, hydroxy, cyano, amino, nitro, —C(O)OR4, C(O)NR7R8, —COR4, —NR4C(O)NR7R8, —OC(O)NR7R8, —NR7C(O)OR4, —S(O)mR4, —NR7R8, C1-4 alkyl, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy, hydroxyC1-4 alkyl, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl;
each R3 is identical or different and each is independently selected from the group consisting of H atom, D atom, halogen, hydroxy, cyano, amino, nitro, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl, 5 to 10 membered heteroaryl, —C(O)R4, —C(O)OR4, —OC(O)NR7R8, —NR7C(O)OR4, —S(O)mR4, —NR7R8 and —C(O)NR7R8, wherein the C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of C1-4 alkyl, hydroxyC1-4 alkyl, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy, halogen, hydroxy, cyano, amino and nitro;
R4 is selected from the group consisting of H atom, D atom, halogen, hydroxy, amino, C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl, wherein the C1-4 alkyl, C1-4 alkoxy, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of C1-4 alkyl, hydroxyC1-4 alkyl, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy, halogen, hydroxy, cyano, amino and nitro;
R5 and R6 are each independently selected from the group consisting of H atom, D atom, C1-4 alkyl, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl, wherein the C1-4 alkyl, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of C1-4 alkyl, hydroxyC1-4 alkyl, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy, halogen, hydroxy, cyano, amino and nitro; or, R5 and R6 together with the atom to which they are attached form a C3-6 cycloalkyl or 3 to 6 membered heterocyclyl, wherein the C3-6 cycloalkyl and 3 to 6 membered heterocyclyl are each independently optionally substituted by one or more substituents selected from the group consisting of halogen, hydroxy, cyano, amino, nitro, C1-4 alkyl, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy, hydroxyC1-4 alkyl, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl;
R7 and R8 are each independently selected from the group consisting of H atom, D atom, C1-4 alkyl, haloC1-4 alkyl, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl, wherein the C1-4 alkyl, haloC1-4 alkyl, C3-6 cycloalkyl, 3 to 6 membered heterocyclyl, C6-10 aryl and 5 to 10 membered heteroaryl are each independently optionally substituted by one or more substituents selected from the group consisting of C1-4 alkyl, hydroxyC1-4 alkyl, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy, halogen, hydroxy, cyano, amino and nitro;
R9 is selected from the group consisting of H atom, D atom and C1-4 alkyl, wherein the C1-4 alkyl is optionally substituted by one or more substituents selected from the group consisting of hydroxyC1-4 alkyl, C1-4 alkoxy, haloC1-4 alkyl, haloC1-4 alkoxy, halogen, hydroxy, cyano, amino and nitro;
m is 0, 1 or 2; and
n is 0, 1, 2, 3 or 4.