US 12,404,275 B2
Pyrazolopyrazine derived compounds, pharmaceutical composition and use thereof
Liguang Dai, Beijing (CN); Li Zhu, Beijing (CN); Hui Zhang, Beijing (CN); Wei Wu, Beijing (CN); Yanqing Yang, Beijing (CN); and Wei Hu, Beijing (CN)
Assigned to PrimeGene (Beijing) Co., Ltd., Beijing (CN)
Appl. No. 17/601,843
Filed by PrimeGene (Beijing) Co., Ltd., Beijing (CN)
PCT Filed Apr. 10, 2020, PCT No. PCT/CN2020/084243
§ 371(c)(1), (2) Date Oct. 6, 2021,
PCT Pub. No. WO2020/207476, PCT Pub. Date Oct. 15, 2020.
Claims priority of application No. 201910294408.7 (CN), filed on Apr. 12, 2019.
Prior Publication US 2022/0204513 A1, Jun. 30, 2022
Int. Cl. C07D 487/04 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [C07D 519/00 (2013.01)] 12 Claims
 
1. A compound represented by general formula (AI) or a pharmaceutically acceptable salt, polymorph, isotopically labelled compound or isomer thereof,

OG Complex Work Unit Chemistry
wherein,
WR1 represents —(CR5R1)— or —(NR1)—;
A represents —OR″ or

OG Complex Work Unit Chemistry
where X′, Y and Z1 independently represent —O—, —S—, —(CO)—, —(CS)—, —(CR6)═, —(CR6R7)—, —N═ or —(NR6)—, and make the formed five-membered ring an unsaturated ring; R6, R7 independently represent substituted or unsubstituted hydrogen, halogen, C1˜6 alkyl, C1˜6 alkoxy, C1˜6 haloalkyl, hydroxy, mercapto, amino, cyano, C1˜4 hydroxyalkylene, C1˜4 mercaptoalkylene, C1˜4 aminoalkylene, C1˜4 cyanoalkylene, —NR9COR10, —COR9 or —CONR9R10;
R″ represents C1-C6 alkyl substituted with hydroxy, methoxy or amino;
R represents substituted or unsubstituted-NR9R10, or R′ and R and the atoms on the ring to which they are connected together form a six-membered heteroaromatic ring;
XR′ represents —(N)— or —(CR′)—; when XR′ represents —(CR′)—, R′ and R and the atoms on the ring to which they are connected together form a six-membered or five-membered aromatic ring or heteroaromatic ring;
YR3 represents —(N)— or —(CR3)—;
Z represents —N— or —CR3—;
R1 represents —(CH2)n—R1′, where R1′ represents substituted or unsubstituted hydrogen, halogen, C1˜6 alkyl, C1˜6 alkoxy, C1˜6 haloalkyl, hydroxy, mercapto, amino, cyano, C3˜8 cycloalkyl, C3˜8 heterocyclyl, C6˜20 aryl, C3˜20 heteroaryl, —NR9COR10, —CONR9R10, —COR9, —SOR9 or —SO2R9, and n represents an integer from 0 to 4;
R2˜R5 independently represent substituted or unsubstituted hydrogen, halogen, C1˜6 alkyl, C1˜6 alkoxy, C1˜6 haloalkyl, hydroxy, mercapto, amino or cyano;
R8 represents —(CH2)n—R8′, where R8′ represents substituted or unsubstituted hydrogen, halogen, C1˜6 alkyl, C1˜6 alkoxy, C1˜6 haloalkyl, hydroxy, mercapto, cyano or —NR9R10, and n represents an integer from 0 to 4;
R9, R10 independently represent substituted or unsubstituted C1˜6 alkyl, C1˜6 alkoxy, or C1˜6 haloalkyl;
the substituents of the above groups, if any, may be selected from halogen, C1˜6 alkyl, C1˜6 haloalkyl, C1˜6 alkoxy, C1˜6 alkylsulfanyl, C3˜8 cycloalkyl, C3˜8 heterocyclyl, C6˜20 aryl, C3˜20 heteroaryl, C1˜6 alkyl ester group, C1˜6 alkyl acyl, C1˜6 alkylsufonyl, amino, hydroxyl, mercapto, carboxyl, nitro, amido, or cyano.