US 11,746,110 B2
Alkynyl (hetero) aromatic ring compounds used for inhibiting protein kinase activity
Yihan Wang, Guangdong (CN); Qingfeng Xing, Guangdong (CN); and Yixin Ai, Guangdong (CN)
Assigned to Shenzhen TargetRx, Inc., Guangdong (CN)
Appl. No. 17/260,787
Filed by Shenzhen TargetRx, Inc., Guangdong (CN)
PCT Filed Jul. 16, 2019, PCT No. PCT/CN2019/096062
§ 371(c)(1), (2) Date Jan. 15, 2021,
PCT Pub. No. WO2020/015615, PCT Pub. Date Jan. 23, 2020.
Claims priority of application No. 201810785390.6 (CN), filed on Jul. 17, 2018; and application No. 201810798080.8 (CN), filed on Jul. 19, 2018.
Prior Publication US 2021/0269448 A1, Sep. 2, 2021
Int. Cl. C07D 487/04 (2006.01)
CPC C07D 487/04 (2013.01) 12 Claims
 
1. A compound of formula (I-1), or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein,
X1, X2, X3 and Y are each independently selected from N and CH, and at least one of X1, X2, X3 and Y is N;
ring A is C6-10 aryl or 5- to 12-membered heteroaryl;
R1 and R3 are each independently absent or are H, halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, —NR12R13, C3-7 cycloalkyl or 4- to 7-membered heterocyclyl, wherein the said C1-6 alkyl is optionally substituted with one, two or three groups selected from C1-3 alkyl, hydroxy and C1-3 alkoxy;
R2 is absent or is C1-6 alkyl, C1-6 alkoxy, C3-7 cycloalkyl or 4- to 7-membered heterocyclyl; wherein the said C1-6 alkyl, C1-6 alkoxy, C3-7 cycloalkyl and 4- to 7-membered heterocyclyl are each optionally substituted by one, two or three R14;
wherein R1 and R2, or R2 and R3 can be combined to form a C5-7 cycloalkyl ring or 5- to 7-membered heterocyclyl ring, and wherein the said C5-7 cycloalkyl ring and 5- to 7-membered heterocyclyl ring are each independently substituted by one, two or three R14;
R4 is H, halogen, hydroxy, amino, C1-6 alkyl, C1-6 alkoxy, C3-7 cycloalkyl or 4- to 7-membered heterocyclyl;
L is selected from —C(O)NR9—, —NR9C(O)— and

OG Complex Work Unit Chemistry
ring B is C6-10 aryl or 5- to 12-membered heteroaryl;
R1 is absent or is H, halogen, cyano, hydroxy, amino, C1-6 alkyl or C1-6 alkoxy;
R6 and R7 are each independently absent or are H, halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C2-6 alkenyl, C2-6 alkynyl, —NR12R13, C3-7 cycloalkyl or 4- to 7-membered heterocyclyl, wherein the said C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C3-7 cycloalkyl and 4- to 7-membered heterocyclyl are optionally substituted by one, two or three R14;
R8 is absent or is H or 5- to 7-membered heteroaryl, wherein the said 5- to 7-membered heteroaryl is optionally substituted by one, two or three R15;
wherein R5 and R6, R6 and R7, or R7 and R8 can be combined to form a C5-7 cycloalkyl ring, 5- to 7-membered heterocyclyl ring, C6-10 aryl ring or 5- to 12-membered heteroaryl ring, and wherein the said C5-7 cycloalkyl ring, 5- to 7-membered heterocyclyl ring, C6-10 aryl ring and 5- to 12-membered heteroaryl ring are each independently substituted by one, two or three R14;
R12 and R13 are each independently H or C1-6 alkyl; or R12 and R13 together with the nitrogen to which they are attached form a 4- to 7-membered heterocyclyl ring, wherein the formed 4- to 7-membered heterocyclyl ring is optionally substituted by one, two or three R15;
each R14 is independently selected from halogen, cyano, hydroxy, C1-6 alkyl, C1-6 alkoxy, —NR16R17, —C(O)NR18R19, C3-7 cycloalkyl and 3- to 7-membered heterocyclyl, wherein the said C3-7 cycloalkyl and 3- to 7-membered heterocyclyl are optionally substituted by one, two or three R15;
each R15 is independently selected from halogen, hydroxy, C1-3 alkyl, C1-3 alkoxy and —NR20R21; and
R9, R16, R17, R18, R19, R20 and R21 are each independently H or C1-3 alkyl.