Pyrazole-containing polycyclic derivative inhibitor, preparation method therefor and application thereof

A compound of formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:

• wherein:
• L1 is selected from the group consisting of a bond, —(CH2)n1—, —(CH2)n1C(O)(CRaaRbb)n2—, —(CH2)n1C(O)NRaa(CH2)n2—, —(CH2)n1(CRaaRbb)n2—, —(CRaaRbb)n1O(CH2)n2—, —(CH2)n1O(CRaaRbb)n2—, —(CRaaRbb)n1S(CH2)n2—, —(CH2)n1S(CRaaRbb)n2—, —(CRaaRbb)n1(CH2)n2NRcc—, —(CH2)n1NRaa(CRbbRcc)n2—, —(CH2)n1NRaaC(O)—, —(CH2)n1P(O)Raa—, —(CH2)n1S(O)n2—, —(CH2)n1S(O)n2NRaa— and —(CH2)n1NRaaS(O)n2—;
• Raa, Rbb, Rcc are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted;
• or, any two of Raa, Rbb, Rcc are bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally further substituted;
• L2 is selected from the group consisting of —(CH2)n3C(O)(CRddRee)n4—, (CH2)n3C(O)NRdd(CH2)n4—, —(CRddRee)n3O(CH2)n4—, —(CH2)n3O(CRddRee)n4—, —(CRddRee)n3S(CH2)n4—, —(CH2)n3S(CRddRee)n4—, —(CRddRee)n3(CH2)n4NRff—, —(CH2)n3NRdd(CReeRff)n4—, —(CH2)n3NRddC(O)—, —(CH2)n3P(O)Rdd—, —(CH2)n3S(O)n4—, —(CH2)n3S(O)n4NRdd— and —(CH2)n3NRddS(O)n4—;
• Rdd, Ree, Rff are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted;
• or, any two of Rdd, Ree, Rff are bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally further substituted;
• ring A is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl;
• R1 is selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted;
• ring B is selected from the group consisting of cycloalkyl, heterocyclyl and heteroaryl;
• R2 is selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted;
• R3 is selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl can be each optionally further substituted;
• Ra is selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, oxo, thioxo, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —(CH2)n5Rgg, —(CH2)n5ORgg, —(CH2)n5C(O)ORgg, —(CH2)n5SRgg, —(CH2)n5NRggC(O)(CH2)n6Rhh, —(CH2)n5NRggC(O)ORhh, —(CH2)n5NRggC(O)NRhhRii, —(CH2)n5NRggRhh, —NRgg(CH2)n5Rhh, —(CH2)n5C(O)NRgg(CH2)n6Rhh, —(CH2)n5C(O)Rgg, —(CH2)n5S(O)n6Rgg, —(CH2)n5NRggS(O)n6Rhh, —CH═CH(CH2)n5Rgg, —CH═CH(CH2)n5NRggRhh, —CH═CH(CH2)n5NRggC(O)Rhh and CH═CH(CH2)n5NRggC(O)NRhhRii, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl can be each optionally further substituted;
• Rgg, Rhh, Rii are each independently selected from the group consisting of hydrogen, deuterium, halogen, amino, nitro, hydroxy, cyano, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy, wherein the amino, alkyl, deuterated alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, heterocyclylalkyl, cycloalkyl, heterocyclyl, aryl, aryloxy, heteroaryl and heteroaryloxy can be each optionally further substituted;
• or, any two of Rgg, Rhh, Rii are bonded to form a cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl or heteroaryl can be optionally further substituted;
• x is an integer from 0 to 6;
• e is an integer from 0 to 6;
• n1, n3, and n5 are each independently an integer from 0 to 3;
• and
• n2, n4, and n6 are each independently an integer from 0 to 2.