[go: up one dir, main page]

WO2024245193A1 - Composé cyclique hétéroaromatique, composition pharmaceutique de celui-ci et utilisation associée - Google Patents

Composé cyclique hétéroaromatique, composition pharmaceutique de celui-ci et utilisation associée Download PDF

Info

Publication number
WO2024245193A1
WO2024245193A1 PCT/CN2024/095527 CN2024095527W WO2024245193A1 WO 2024245193 A1 WO2024245193 A1 WO 2024245193A1 CN 2024095527 W CN2024095527 W CN 2024095527W WO 2024245193 A1 WO2024245193 A1 WO 2024245193A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
substituted
independently
membered
halogen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/CN2024/095527
Other languages
English (en)
Chinese (zh)
Inventor
姜佳俊
罗会兵
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shanghai Allist Pharmaceuticals Inc
Original Assignee
Shanghai Allist Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shanghai Allist Pharmaceuticals Inc filed Critical Shanghai Allist Pharmaceuticals Inc
Publication of WO2024245193A1 publication Critical patent/WO2024245193A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the invention relates to a heteroaromatic ring compound, a pharmaceutical composition thereof and application thereof.
  • the fibroblast growth factor receptor (FGFR) family belongs to receptor tyrosine protein kinases (RTKs), including four receptor subtypes (FGFR1, FGFR2, FGFR3 and FGFR4).
  • RTKs receptor tyrosine protein kinases
  • FGFR dimerization after fibroblast growth factor binds to the FGFR receptor, it induces FGFR dimerization and phosphorylates the tyrosine at the end of the FGFR cytoplasmic structure, activating the downstream FRS2-Ras-MAPK, PLC ⁇ and PI3K-AKT/PKB signaling pathways.
  • the FGFR signaling pathway is involved in regulating multiple processes such as embryonic development, cell proliferation and migration, and angiogenesis.
  • the FGF in the human body is divided into 6 subfamilies, which are divided into two categories: classical FGFs and hormone FGFs.
  • Classical FGFs include FGF1-10, 16-18, 20, and 22, which can bind to FGFR1-4
  • hormone FGFs include FGF19, 21, and 23, which mainly bind to FGFR1 and FGFR4.
  • FGF19-FGFR4 regulates bile acid metabolism
  • FGF23-FGFR1 regulates calcium, phosphorus, and vitamin D levels in the blood (C. Degirolamo et al., Nat Rev Drug Discov. 2016; 15: 51-69). This makes the inhibition of FGFR1 and FGFR4 cause target-related toxicity, causing severe adverse reactions such as hyperphosphatemia and diarrhea.
  • FGFR mutation activation or high expression is closely related to the occurrence and development of human tumors.
  • FGFR activation mutation or overexpression in cells can lead to the persistence and overactivation of the FGFR signaling pathway, causing cells to acquire carcinogenic functions such as excessive proliferation and apoptosis escape.
  • FGFR abnormalities including FGFR1 (49%), FGFR2 (19%), FGFR3 (26%) and FGFR4 (7%).
  • the incidence of FGFR2 abnormalities is higher in endometrial cancer, bile duct cancer and gastric cancer (T. Helsten et al., Clin Cancer Res. 2016, 22: 259-267).
  • pan-FGFR inhibitors on the market, such as the pan-FGFR inhibitors Erdatinib and Pemigatinib, both of which cause severe adverse reactions such as hyperphosphatemia and diarrhea due to the inhibition of FGFR1 and FGFR4.
  • pan-FGFR inhibitors can also develop drug resistance during treatment. These adverse reactions and acquired drug resistance problems greatly limit the application of pan-FGFR inhibitors.
  • RLY-4008 is the first selective FGFR2 inhibitor developed by RELAY THERAPEUTICS, INC. and is currently in the clinical stage. Its structure is disclosed in WO2020231990 A1 as follows:
  • the technical problem to be solved by the present invention is to overcome the defect of insufficient types of FGFR2 inhibitors in the prior art, and to provide a novel heteroaromatic compound, a pharmaceutical composition thereof and its application.
  • the compound of the present invention has good inhibitory activity and selectivity against FGFR2 abnormality, and has good proliferation inhibitory activity against human gastric cancer cell SNU-16, and has good selectivity against human small cell lung cancer cell DMS114 and human bladder cancer cell RT112/84.
  • the present invention solves the above technical problems through the following methods.
  • the present invention provides a compound represented by formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:
  • X is CR X or N
  • RX is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N( R6 ) 2 , C1-6 alkyl, -OC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkyl substituted by one or more halogens;
  • each R 6 is independently hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 6a , C 3-8 cycloalkyl substituted by one or more R 6b , 3-10 membered heterocycloalkyl substituted by one or more R 6c , C 6-10 aryl substituted by one or more R 6d , or 5-10 membered heteroaryl substituted by one or more R 6e ;
  • R 6 or two R 6 together with the nitrogen atom to which they are commonly attached form a 3-10 membered heterocyclic hydrocarbon group or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 6f ;
  • R 6a , R 6b , R 6c , R 6d , R 6e and R 6f is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • R 1 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N(R 6 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, -C(O)N(R 6 ) 2 , -C(O)R 6 , -C(O)OR 6 , -SO 2 R 6 , -SO 2 N(R 6 ) 2 , C 1-6 alkyl substituted by one or more R 1a , -OC 1-6 alkyl substituted by one or more R 1b , C 2-6 alkenyl substituted by one or more R 1c , C 2-6 alkynyl substituted by one or more R 1d , C 3-8 cycloalkyl substituted by one or more R 1e
  • R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , R 1g and R 1h is independently deuterium, halogen, cyano, hydroxyl, -N(R 6 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 1-a , -OC 1-6 alkyl substituted by one or more R 1-b , C 2-6 alkenyl substituted by one or more R 1-c , C 2-6 alkynyl substituted by one or more R 1-d , C 3-8 cycloalkyl substituted by one or more R 1-e , 1-f substituted 3-10 membered heterocyclic hydrocarbon group, C 6-10 aryl group
  • R 1-a , R 1-b , R 1-c , R 1-d , R 1-e , R 1-f , R 1-g and R 1-h is independently deuterium, halogen, cyano, —NH 2 , hydroxyl, C 1-6 alkyl or —OC 1-6 alkyl;
  • Ring A is a C 3-8 cycloalkyl, a 3-10 membered heterocycloalkyl, a C 6-10 aryl or a 5-10 membered heteroaryl;
  • each R2 is independently halogen, cyano, C1-6 alkyl, -OC1-6 alkyl, -SC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, nitro, -N( R8 ) 2 , -S(O) 2 ( R8 ), -S(O) 2N ( R8 ) 2 , -S(O)( R8 ), -S(O)N( R8 ) 2 , -C(O)( R8 ), -C(O)O( R8 ), -C(O)O( R8 ), -C(O)N( R8 ) 2 , -OC(O)( R8 ), -OC(O)N( R8 ) 2 , -N( R8 )C(O)O( R8 ), -N( R8 )C(O)O( R8 ), -N( R8 )C(O)( R8 ), -N( R
  • Each R 2a is independently deuterium, halogen, cyano, -N(R 2-a ) 2 , hydroxy, C 1-6 alkyl or -OC 1-6 alkyl;
  • Each R 2-a is independently hydrogen or C 1-6 alkyl
  • n 0, 1, 2, 3, 4 or 5;
  • Each R 8 is independently hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, C 1-6 alkyl substituted by one or more R 8a , or C 3-8 cycloalkyl substituted by one or more R 8b ;
  • each R 8a and R 8b is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted by one or more R 8-a , C 3-8 cycloalkyl, or C 3-8 cycloalkyl substituted by one or more R 8-b ;
  • R 8-a and R 8-b are independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • Ring B is a C 3-8 cycloalkylene group, a 3-10 membered heterocycloalkylene group, a C 6-10 arylene group, or a 5-10 membered heteroarylene group;
  • each R3 is independently deuterium, halogen, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, nitro, -O( R6 ), -S( R6 ), -N( R6 ) 2, -S(O)2 ( R6 ), -S(O) 2N ( R6 ) 2 , -S(O)( R6 ), -S(O)N( R6 ) 2 , -C(O)(R6), -C(O)O( R6 ), -C(O)N( R6 ) 2 , -OC(O)( R6 ), -OC(O)N( R6 ) 2 , -N( R6 )C(O)O( R6 ) , -N(R6)C(O)( R6 ), -N( R6 )C(O)O( R6 ) 2 , -N(R6)C(O)( R6
  • Each R 3a is independently deuterium, halogen, cyano, -N(R 6 ) 2 , hydroxy, C 1-6 alkyl or -OC 1-6 alkyl;
  • n 0, 1, 2, 3 or 4;
  • L is a covalent bond, C 1-6 alkylene, -N( RL )-, -N( RL )C(O)-, -C(O)N( RL )-, -N( RL )S(O) 2- , -S(O)2N( RL )-, -O-, -C(O)-, -OC(O)-, -C(O )O-, -S-, -S(O)-, or -S(O)2- ;
  • each RL is independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C1-6 alkyl substituted by one or more RL , C3-8 cycloalkyl substituted by one or more RLb , 3-10 membered heterocycloalkyl substituted by one or more RLc , C6-10 aryl substituted by one or more RLd , or 5-10 membered heteroaryl substituted by one or more RLe ;
  • R La , R Lb , R Lc , R Ld and R Le is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • R7 is halogen, cyano,
  • R 7a , R 7b and R 7c are each independently hydrogen, deuterium, halogen, cyano, —C(O)(R 6 ), —C(O)O(R 6 ), —C(O)N(R 6 ) 2 , C 1-6 alkyl, C 1-6 alkyl substituted by one or more R 7-a , C 2-6 alkenyl, C 2-6 alkenyl substituted by one or more R 7-b, C 2-6 alkynyl, C 2-6 alkynyl substituted by one or more R 7-c, C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 7-d , 3-10 membered heterocycloalkyl , 3-10 membered heterocycloalkyl substituted by one or more R 7-e , C 6-10 aryl, C 6-10 aryl substituted by one or more R 7-f , 5-10 membered heteroaryl, or substituted by one or more
  • R 7-a , R 7-b , R 7-c , R 7-d , R 7-e , R 7-f and R 7-g is independently deuterium, halogen, cyano, -N(R 6 ) 2 , hydroxyl, C 1- 6 alkyl, -OC 1-6 alkyl, C 3-8 cycloalkyl or 3-10 membered heterocycloalkyl;
  • R 4 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N(R 6 ) 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 4a , C 2-6 alkenyl substituted by one or more R 4b , C 2-6 alkynyl substituted by one or more R 4c , C 3-8 cycloalkyl substituted by one or more R 4d , 3-10 membered heterocycloalkyl substituted by one or more R 4e , C 6-10 aryl substituted by one or more R 4f , or 5-10 membered heteroaryl substituted by one or more R 4g ;
  • each of R 4a , R 4b , R 4c , R 4d , R 4e , R 4f and R 4g is independently deuterium, halogen, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, nitro, -O(R 6 ), -S(R 6 ), -N(R 6 ) 2 , -S(O) 2 (R 6 ) , -S(O) 2 N(R 6 ) 2 , -S(O)(R 6 ), -S(O)N(R 6 ) 2 , -C(O)(R 6 ), -C(O)O(R 6 ), -C(O)O(R 6 ), -C(O)N(R 6 ) 2 , -OC(O)(R 6 ), -OC(O)N(R 6 ) 2 , -N(R 6 )C(O)O(R 6 ), -
  • R 5 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -NR 9 R 10 , -S(R 9 ), -S(O) 2 (R 11 ), -S(O) 2 N(R 9 ) 2 , -S(O)(R 11 ), -S(O)N(R 9 ) 2 , -C(O)(R 11 ), -C(O)O(R 9 ), -C( -P(O)(R 18 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl , C 2-6 alkenyl , C 2-6 alkynyl , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl , C 6-10 aryl, 5-10 membered heteroaryl , C 1-6 alkyl substituted by one or more R 5a, C 1-6 alkyl substituted by one or more R 5a -OC 1-6 alkyl substituted by one
  • each of R 5a , R 5b , R 5c , R 5d , R 5e , R 5f , R 5g and R 5h is independently deuterium, halogen, hydroxy, cyano, nitro, -NR 9 R 10 , -S(R 9 ), -S(O) 2 (R 11 ), -S(O) 2 N(R 9 ) 2 , -S(O)(R 11 ), -S(O)N(R 9 ) 2 , -C(O)(R 11 ), -C(O)O(R 9 ), -C(O)N(R 9 ) 2 , -OC(O)(R 9 ), -OC(O)N(R 9 ) 2 , -N(R 9 )C(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -N(R 9
  • Each R 15 is independently C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 15a , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted by one or more R 15b ;
  • R 15a and R 15b are independently deuterium, halogen, cyano, hydroxy, -NH 2 , C 1-6 alkyl or -OC 1-6 alkyl;
  • each of R 5-a , R 5-b , R 5-c , R 5-d , R 5-e , R 5-f , R 5-g and R 5-h is independently deuterium, halogen, cyano, hydroxyl, oxo ( ⁇ O), —N(R 12 ) 2 , C 1-6 alkyl, —OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 5-a-1 , —OC 1-6 alkyl substituted by one or more R 5-a-2 , C 3-8 cycloalkyl substituted by one or more R 5-a-3 , or 3-12 membered heterocycloalkyl substituted by one or more R 5-a-4 ;
  • R 5-a-1 , R 5-a-2 , R 5-a-3 and R 5-a-4 is independently deuterium, C 1-6 alkyl, halogen, cyano, hydroxyl or -N(R 12 ) 2 ;
  • Each R 12 is independently hydrogen or C 1-6 alkyl
  • each R 9 and R 10 is independently hydrogen, hydroxy, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 9a , C 3-8 cycloalkyl substituted by one or more R 9b , 3-12 membered heterocycloalkyl substituted by one or more R 9c , C 6-10 aryl substituted by one or more R 9d , or 5-10 membered heteroaryl substituted by one or more R 9e ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9a , R 9b , R 9c , R 9d , R 9e and R 9f is independently —S(O) 2 (R 19 ), deuterium, halogen, cyano, —N(R 14 ) 2 , hydroxy, oxo ( ⁇ O), C 1-6 alkyl, —OC 1-6 alkyl, C 1-6 alkyl substituted by one or more R 9-a , —OC 1-6 alkyl substituted by one or more R 9-b , 3-12 membered heterocyclic hydrocarbon group, 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9-c, C 3-8 cycloalkyl group, or substituted by one or more R 9-c ; a C 3-8 cycloalkyl group substituted with multiple R 9-d ;
  • R 9-a , R 9-b , R 9-c and R 9-d is independently deuterium, C 1-6 alkyl, hydroxyl, halogen, cyano, -S(O) 2 (R 17 ), -NH 2 , -NH(R 16 ) or -N(R 16 ) 2 ;
  • each R 11 is independently hydrogen, halogen, hydroxy, C 1-6 alkyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 11a , C 3-8 cycloalkyl substituted by one or more R 11b , 3-10 membered heterocycloalkyl substituted by one or more R 11c , C 6-10 aryl substituted by one or more R 11d , or 5-10 membered heteroaryl substituted by one or more R 11e ;
  • R 11a , R 11b , R 11c , R 11d and R 11e is independently deuterium, halogen, cyano, —NH 2 , hydroxyl, C 1-6 alkyl or —OC 1-6 alkyl;
  • Each R 13 is independently hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, or 3-10 membered heterocycloalkyl;
  • Each R 14 is independently hydrogen or C 1-6 alkyl
  • Each R 16 is independently C 1-6 alkyl, C 3-8 cycloalkyl or 3-10 membered heterocycloalkyl;
  • Each R 17 is independently hydrogen, halogen, hydroxy, C 1-6 alkyl, C 3-8 cycloalkyl or 3-10 membered heterocycloalkyl;
  • Each R 18 is independently hydrogen, hydroxy, C 1-6 alkyl, C 3-8 cycloalkyl, or 3-10 membered heterocycloalkyl;
  • Each R 19 is independently hydrogen, halogen, hydroxy, C 1-6 alkyl, C 3-8 cycloalkyl or 3-10 membered heterocycloalkyl;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2, 3 or 4;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • the present invention provides a compound represented by formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:
  • X is CR X or N
  • RX is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N( R6 ) 2 , C1-6 alkyl, -OC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkyl substituted by one or more halogens;
  • each R 6 is independently hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 6a , C 3-8 cycloalkyl substituted by one or more R 6b , 3-10 membered heterocycloalkyl substituted by one or more R 6c , C 6-10 aryl substituted by one or more R 6d , or 5-10 membered heteroaryl substituted by one or more R 6e ;
  • R 6 or two R 6 together with the nitrogen atom to which they are commonly attached form a 3-10 membered heterocyclic hydrocarbon group or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 6f ;
  • R 6a , R 6b , R 6c , R 6d , R 6e and R 6f is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • R 1 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N(R 6 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, -C(O)N(R 6 ) 2 , -C(O)R 6 , -C(O)OR 6 , -SO 2 R 6 , -SO 2 N(R 6 ) 2 , C 1-6 alkyl substituted by one or more R 1a , -OC 1-6 alkyl substituted by one or more R 1b , C 2-6 alkenyl substituted by one or more R 1c , C 2-6 alkynyl substituted by one or more R 1d , C 3-8 cycloalkyl substituted by one or more R 1e
  • R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , R 1g and R 1h is independently deuterium, halogen, cyano, hydroxyl, -N(R 6 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 1-a , -OC 1-6 alkyl substituted by one or more R 1-b , C 2-6 alkenyl substituted by one or more R 1-c , C 2-6 alkynyl substituted by one or more R 1-d , C 3-8 cycloalkyl substituted by one or more R 1-e , 1-f substituted 3-10 membered heterocyclic hydrocarbon group, C 6-10 aryl group
  • R 1-a , R 1-b , R 1-c , R 1-d , R 1-e , R 1-f , R 1-g and R 1-h is independently deuterium, halogen, cyano, —NH 2 , hydroxyl, C 1-6 alkyl or —OC 1-6 alkyl;
  • Ring A is a C 3-8 cycloalkyl, a 3-10 membered heterocycloalkyl, a C 6-10 aryl or a 5-10 membered heteroaryl;
  • each R2 is independently halogen, cyano, C1-6 alkyl, -OC1-6 alkyl, -SC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, nitro, -N( R8 ) 2 , -S(O) 2 ( R8 ), -S(O) 2N ( R8 ) 2 , -S(O)( R8 ), -S(O)N( R8 ) 2 , -C(O)( R8 ), -C(O)O( R8 ), -C(O)O( R8 ), -C(O)N( R8 ) 2 , -OC(O)( R8 ), -OC(O)N( R8 ) 2 , -N( R8 )C(O)O( R8 ), -N( R8 )C(O)O( R8 ), -N( R8 )C(O)( R8 ), -N( R
  • Each R 2a is independently deuterium, halogen, cyano, -N(R 2-a ) 2 , hydroxy, C 1-6 alkyl or -OC 1-6 alkyl;
  • Each R 2-a is independently hydrogen or C 1-6 alkyl
  • n 0, 1, 2, 3, 4 or 5;
  • Each R 8 is independently hydrogen, C 1-6 alkyl, or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • Ring B is a C 3-8 cycloalkylene group, a 3-10 membered heterocycloalkylene group, a C 6-10 arylene group, or a 5-10 membered heteroarylene group;
  • each R3 is independently deuterium, halogen, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, nitro, -O( R6 ), -S( R6 ), -N( R6 ) 2 , -S(O) 2 ( R6 ), -S(O) 2N ( R6 ) 2 , -S(O)( R6 ), -S(O)N( R6 ) 2 , -C(O)( R6 ), -C(O)O( R6 ), -C(O)N( R6 ) 2 , -OC(O)( R6 ), -OC(O)N( R6 ) 2 , -N( R6 )C(O)O( R6 ), -N(R6)C(O)( R6 ), -N( R6 )C(O)N( R6 )2, R 6 ) 2 , -N(R 6
  • Each R 3a is independently deuterium, halogen, cyano, -N(R 6 ) 2 , hydroxy, C 1-6 alkyl or -OC 1-6 alkyl;
  • n 0, 1, 2, 3 or 4;
  • L is a covalent bond, C 1-6 alkylene, -N( RL )-, -N( RL )C(O)-, -C(O)N( RL )-, -N( RL )S(O) 2- , -S(O)2N( RL )-, -O-, -C(O)-, -OC(O)-, -C(O )O-, -S-, -S(O)-, or -S(O)2- ;
  • each RL is independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C1-6 alkyl substituted by one or more RL , C3-8 cycloalkyl substituted by one or more RLb , 3-10 membered heterocycloalkyl substituted by one or more RLc , C6-10 aryl substituted by one or more RLd , or 5-10 membered heteroaryl substituted by one or more RLe ;
  • R La , R Lb , R Lc , R Ld and R Le is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • R7 is halogen, cyano,
  • R 7a , R 7b and R 7c are each independently hydrogen, deuterium, halogen, cyano, —C(O)(R 6 ), —C(O)O(R 6 ), —C(O)N(R 6 ) 2 , C 1-6 alkyl, C 1-6 alkyl substituted by one or more R 7-a , C 2-6 alkenyl, C 2-6 alkenyl substituted by one or more R 7-b, C 2-6 alkynyl, C 2-6 alkynyl substituted by one or more R 7-c, C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 7-d , 3-10 membered heterocycloalkyl , 3-10 membered heterocycloalkyl substituted by one or more R 7-e , C 6-10 aryl, C 6-10 aryl substituted by one or more R 7-f , 5-10 membered heteroaryl, or substituted by one or more
  • R 7-a , R 7-b , R 7-c , R 7-d , R 7-e , R 7-f and R 7-g is independently deuterium, halogen, cyano, -N(R 6 ) 2 , hydroxyl, C 1- 6 alkyl or -OC 1-6 alkyl;
  • R 4 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N(R 6 ) 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 4a , C 2-6 alkenyl substituted by one or more R 4b , C 2-6 alkynyl substituted by one or more R 4c , C 3-8 cycloalkyl substituted by one or more R 4d , 3-10 membered heterocycloalkyl substituted by one or more R 4e , C 6-10 aryl substituted by one or more R 4f , or 5-10 membered heteroaryl substituted by one or more R 4g ;
  • each of R 4a , R 4b , R 4c , R 4d , R 4e , R 4f and R 4g is independently deuterium, halogen, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, nitro, -O(R 6 ), -S(R 6 ), -N(R 6 ) 2 , -S(O) 2 (R 6 ) , -S(O) 2 N(R 6 ) 2 , -S(O)(R 6 ), -S(O)N(R 6 ) 2 , -C(O)(R 6 ), -C(O)O(R 6 ), -C(O)O(R 6 ), -C(O)N(R 6 ) 2 , -OC(O)(R 6 ), -OC(O)N(R 6 ) 2 , -N(R 6 )C(O)O(R 6 ), -
  • R 5 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, - NR 9 R 10 , -S(R 9 ), -S(O) 2 (R 11 ), -S(O) 2 N(R 9 ) 2 , -S(O)(R 11 ), -S(O)N(R 9 ) 2 , -C(O)(R 11 ), -C(O)O(R 9 ), -C(O)N(R 9 ) 2 , -OC(O)(R 9 ), -OC(O)N(R 9 ) 2 , -N(R 9 )C(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -N(R 9 )C(O)(R 9 ), -N(R 9 )C(O)(R 9 ), -N(R 9 )C(O)(R 9 ), -N(R 9 )
  • each of R 5a , R 5b , R 5c , R 5d , R 5e , R 5f , R 5g and R 5h is independently deuterium, halogen, hydroxy, cyano, nitro, -NR 9 R 10 , -S(R 9 ), -S(O) 2 (R 11 ), -S(O) 2 N(R 9 ) 2 , -S(O)(R 11 ), -S(O)N(R 9 ) 2 , -C(O)(R 11 ), -C(O)O(R 9 ), -C(O)N(R 9 ) 2 , -OC(O)(R 9 ), -OC(O)N(R 9 ) 2 , -N(R 9 )C(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -N(R 9
  • Each R 15 is independently C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 15a , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted by one or more R 15b ;
  • R 15a and R 15b are independently deuterium, halogen, cyano, hydroxy, -NH 2 , C 1-6 alkyl or -OC 1-6 alkyl;
  • each of R 5-a , R 5-b , R 5-c , R 5-d , R 5-e , R 5-f , R 5-g and R 5-h is independently deuterium, halogen, cyano, hydroxyl, oxo ( ⁇ O), —N(R 12 ) 2 , C 1-6 alkyl, —OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 5-a-1 , —OC 1-6 alkyl substituted by one or more R 5-a-2 , C 3-8 cycloalkyl substituted by one or more R 5-a-3 , or 3-12 membered heterocycloalkyl substituted by one or more R 5-a-4 ;
  • R 5-a-1 , R 5-a-2 , R 5-a-3 and R 5-a-4 is independently deuterium, halogen, cyano, hydroxyl or -N(R 12 ) 2 ;
  • Each R 12 is independently hydrogen or C 1-6 alkyl
  • each R 9 and R 10 is independently hydrogen, hydroxy, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 9a , C 3-8 cycloalkyl substituted by one or more R 9b , 3-12 membered heterocycloalkyl substituted by one or more R 9c , C 6-10 aryl substituted by one or more R 9d , or 5-10 membered heteroaryl substituted by one or more R 9e ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9a , R 9b , R 9c , R 9d , R 9e and R 9f is independently -S(O) 2 (R 19 ), deuterium, halogen, cyano, -N(R 14 ) 2 , hydroxy, oxo ( ⁇ O), C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted by one or more R 9-a , C 1-6 alkyl substituted by one or more R 9-b -OC 1-6 alkyl, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 9-c , C 3-8 cycloalkyl, or C 3-8 cycloalkyl substituted by one or more R 9-d ;
  • R 9-a , R 9-b , R 9-c and R 9-d is independently deuterium, C 1-6 alkyl, hydroxyl, halogen, cyano, -S(O) 2 (R 17 ), -NH 2 , -NH(R 16 ) or -N(R 16 ) 2 ;
  • each R 11 is independently hydrogen, halogen, hydroxy, C 1-6 alkyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 11a , C 3-8 cycloalkyl substituted by one or more R 11b , 3-10 membered heterocycloalkyl substituted by one or more R 11c , C 6-10 aryl substituted by one or more R 11d , or 5-10 membered heteroaryl substituted by one or more R 11e ;
  • R 11a , R 11b , R 11c , R 11d and R 11e is independently deuterium, halogen, cyano, —NH 2 , hydroxyl, C 1-6 alkyl or —OC 1-6 alkyl;
  • Each R 13 is independently hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, or 3-10 membered heterocycloalkyl;
  • Each R 14 is independently hydrogen or C 1-6 alkyl
  • Each R 16 is independently C 1-6 alkyl, C 3-8 cycloalkyl or 3-10 membered heterocycloalkyl;
  • Each R 17 is independently hydrogen, halogen, hydroxy, C 1-6 alkyl, C 3-8 cycloalkyl or 3-10 membered heterocycloalkyl;
  • Each R 18 is independently hydrogen, hydroxy, C 1-6 alkyl, C 3-8 cycloalkyl, or 3-10 membered heterocycloalkyl;
  • Each R 19 is independently hydrogen, halogen, hydroxy, C 1-6 alkyl, C 3-8 cycloalkyl or 3-10 membered heterocycloalkyl;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • the present invention provides a compound represented by formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:
  • X is CR X or N
  • RX is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N( R6 ) 2 , C1-6 alkyl, -OC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkyl substituted by one or more halogens;
  • each R 6 is independently hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 6a , C 3-8 cycloalkyl substituted by one or more R 6b , 3-10 membered heterocycloalkyl substituted by one or more R 6c , C 6-10 aryl substituted by one or more R 6d , or 5-10 membered heteroaryl substituted by one or more R 6e ;
  • R 6 or two R 6 together with the nitrogen atom to which they are commonly attached form a 3-10 membered heterocyclic hydrocarbon group or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 6f ;
  • R 6a , R 6b , R 6c , R 6d , R 6e and R 6f is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • R 1 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N(R 6 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, -C(O)N(R 6 ) 2 , -C(O)R 6 , -C(O)OR 6 , -SO 2 R 6 , -SO 2 N(R 6 ) 2 , C 1-6 alkyl substituted by one or more R 1a , -OC 1-6 alkyl substituted by one or more R 1b , C 2-6 alkenyl substituted by one or more R 1c , C 2-6 alkynyl substituted by one or more R 1d , C 3-8 cycloalkyl substituted by one or more R 1e
  • R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , R 1g and R 1h is independently deuterium, halogen, cyano, hydroxyl, -N(R 6 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 1-a , -OC 1-6 alkyl substituted by one or more R 1-b , C 2-6 alkenyl substituted by one or more R 1-c , C 2-6 alkynyl substituted by one or more R 1-d , C 3-8 cycloalkyl substituted by one or more R 1-e , 1-f substituted 3-10 membered heterocyclic hydrocarbon group, C 6-10 aryl group
  • R 1-a , R 1-b , R 1-c , R 1-d , R 1-e , R 1-f , R 1-g and R 1-h is independently deuterium, halogen, cyano, —NH 2 , hydroxyl, C 1-6 alkyl or —OC 1-6 alkyl;
  • Ring A is a C 3-8 cycloalkyl, a 3-10 membered heterocycloalkyl, a C 6-10 aryl or a 5-10 membered heteroaryl;
  • each R2 is independently halogen, cyano, C1-6 alkyl, -OC1-6 alkyl, -SC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, nitro, -N( R8 ) 2 , -S(O) 2 ( R8 ), -S(O) 2N ( R8 ) 2 , -S(O)( R8 ), -S(O)N( R8 ) 2 , -C(O)( R8 ), -C(O)O( R8 ), -C(O)O( R8 ), -C(O)N( R8 ) 2 , -OC(O)( R8 ), -OC(O)N( R8 ) 2 , -N( R8 )C(O)O( R8 ), -N( R8 )C(O)O( R8 ), -N( R8 )C(O)( R8 ), -N( R
  • Each R 2a is independently deuterium, halogen, cyano, -N(R 2-a ) 2 , hydroxy, C 1-6 alkyl or -OC 1-6 alkyl;
  • Each R 2-a is independently hydrogen or C 1-6 alkyl
  • n 0, 1, 2, 3, 4 or 5;
  • Each R 8 is independently hydrogen, C 1-6 alkyl, or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • Ring B is a C 3-8 cycloalkylene group, a 3-10 membered heterocycloalkylene group, a C 6-10 arylene group, or a 5-10 membered heteroarylene group;
  • each R3 is independently deuterium, halogen, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, nitro, -O( R6 ), -S( R6 ), -N( R6 ) 2 , -S(O) 2 ( R6 ), -S(O) 2N ( R6 ) 2 , -S(O)( R6 ), -S(O)N( R6 ) 2 , -C(O)( R6 ), -C(O)O( R6 ), -C(O)N( R6 ) 2 , -OC(O)( R6 ), -OC(O)N( R6 ) 2 , -N( R6 )C(O)O( R6 ), -N(R6)C(O)( R6 ), -N( R6 )C(O)N( R6 )2, R 6 ) 2 , -N(R 6
  • Each R 3a is independently deuterium, halogen, cyano, -N(R 6 ) 2 , hydroxy, C 1-6 alkyl or -OC 1-6 alkyl;
  • n 0, 1, 2, 3 or 4;
  • L is a covalent bond, C 1-6 alkylene, -N( RL )-, -N( RL )C(O)-, -C(O)N( RL )-, -N( RL )S(O) 2- , -S(O)2N( RL )-, -O-, -C(O)-, -OC(O)-, -C(O )O-, -S-, -S(O)-, or -S(O)2- ;
  • each RL is independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C1-6 alkyl substituted by one or more RL , C3-8 cycloalkyl substituted by one or more RLb , 3-10 membered heterocycloalkyl substituted by one or more RLc , C6-10 aryl substituted by one or more RLd , or 5-10 membered heteroaryl substituted by one or more RLe ;
  • R La , R Lb , R Lc , R Ld and R Le is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • R7 is halogen, cyano,
  • R 7a , R 7b and R 7c are each independently hydrogen, deuterium, halogen, cyano, —C(O)(R 6 ), —C(O)O(R 6 ), —C(O)N(R 6 ) 2 , C 1-6 alkyl, C 1-6 alkyl substituted by one or more R 7-a , C 2-6 alkenyl, C 2-6 alkenyl substituted by one or more R 7-b, C 2-6 alkynyl, C 2-6 alkynyl substituted by one or more R 7-c, C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 7-d , 3-10 membered heterocycloalkyl , 3-10 membered heterocycloalkyl substituted by one or more R 7-e , C 6-10 aryl, C 6-10 aryl substituted by one or more R 7-f , 5-10 membered heteroaryl, or substituted by one or more
  • R 7-a , R 7-b , R 7-c , R 7-d , R 7-e , R 7-f and R 7-g is independently deuterium, halogen, cyano, -N(R 6 ) 2 , hydroxyl, C 1- 6 alkyl or -OC 1-6 alkyl;
  • R 4 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N(R 6 ) 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 4a , C 2-6 alkenyl substituted by one or more R 4b , C 2-6 alkynyl substituted by one or more R 4c , C 3-8 cycloalkyl substituted by one or more R 4d , 3-10 membered heterocycloalkyl substituted by one or more R 4e , C 6-10 aryl substituted by one or more R 4f , or 5-10 membered heteroaryl substituted by one or more R 4g ;
  • each of R 4a , R 4b , R 4c , R 4d , R 4e , R 4f and R 4g is independently deuterium, halogen, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, nitro, -O(R 6 ), -S(R 6 ), -N(R 6 ) 2 , -S(O) 2 (R 6 ) , -S(O) 2 N(R 6 ) 2 , -S(O)(R 6 ), -S(O)N(R 6 ) 2 , -C(O)(R 6 ), -C(O)O(R 6 ), -C(O)O(R 6 ), -C(O)N(R 6 ) 2 , -OC(O)(R 6 ), -OC(O)N(R 6 ) 2 , -N(R 6 )C(O)O(R 6 ), -
  • R5 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -NR9R10 , -S( R9 ), -S(O) 2 ( R11 ), -S(O) 2N ( R9 ) 2 , -S(O)( R11 ), -S(O)N( R9 ) 2 , -C(O)( R11 ), -C(O)O( R9 ), -C (O)N( R9 ) 2 , -OC(O)( R9 ), -OC(O)N( R9 ) 2 , -N( R9 )C(O)O( R9 ), -N( R9)C(O)(R9), -N(R9 ) C (O)N( R9 ) 2 , -N( R9 )S(O) 2N ( R9 ) 2 , -N(R 9 )S(O) 2 (R 9 ), C 1-6
  • each of R 5a , R 5b , R 5c , R 5d , R 5e , R 5f , R 5g and R 5h is independently deuterium, halogen, hydroxy, cyano, nitro, -NR 9 R 10 , -S(R 9 ), -S(O) 2 (R 11 ), -S(O) 2 N(R 9 ) 2 , -S(O)(R 11 ), -S(O)N(R 9 ) 2 , -C(O)(R 11 ), -C(O)O(R 9 ), -C(O)N(R 9 ) 2 , -OC(O)(R 9 ), -OC(O)N(R 9 ) 2 , -N(R 9 )C(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -N(R 9
  • Each R 15 is independently C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 15a , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted by one or more R 15b ;
  • R 15a and R 15b are independently deuterium, halogen, cyano, hydroxy, -NH 2 , C 1-6 alkyl or -OC 1-6 alkyl;
  • each of R 5-a , R 5-b , R 5-c , R 5-d , R 5-e , R 5-f , R 5-g and R 5-h is independently deuterium, halogen, cyano, hydroxyl, oxo ( ⁇ O), —N(R 12 ) 2 , C 1-6 alkyl, —OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 5-a-1 , —OC 1-6 alkyl substituted by one or more R 5-a-2 , C 3-8 cycloalkyl substituted by one or more R 5-a-3 , or 3-12 membered heterocycloalkyl substituted by one or more R 5-a-4 ;
  • R 5-a-1 , R 5-a-2 , R 5-a-3 and R 5-a-4 is independently deuterium, halogen, cyano, hydroxyl or -N(R 12 ) 2 ;
  • Each R 12 is independently hydrogen or C 1-6 alkyl
  • each R 9 and R 10 is independently hydrogen, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 9a , C 3-8 cycloalkyl substituted by one or more R 9b , 3-12 membered heterocycloalkyl substituted by one or more R 9c , C 6-10 aryl substituted by one or more R 9d , or 5-10 membered heteroaryl substituted by one or more R 9e ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each of R 9a , R 9b , R 9c , R 9d , R 9e and R 9f is independently deuterium, halogen, cyano, -N(R 14 ) 2 , hydroxy, oxo, C 1- 6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted by one or more R 9-a , -OC 1-6 alkyl substituted by one or more R 9-b , 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 9-c , C 3-8 cycloalkyl, or C 3-8 cycloalkyl substituted by one or more R 9-d ;
  • R 9-a , R 9-b , R 9-c and R 9-d is independently deuterium, hydroxyl, halogen, cyano or -NH 2 ;
  • each R 11 is independently hydrogen, halogen, hydroxy, C 1-6 alkyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 11a , C 3-8 cycloalkyl substituted by one or more R 11b , 3-10 membered heterocycloalkyl substituted by one or more R 11c , C 6-10 aryl substituted by one or more R 11d , or 5-10 membered heteroaryl substituted by one or more R 11e ;
  • R 11a , R 11b , R 11c , R 11d and R 11e is independently deuterium, halogen, cyano, —NH 2 , hydroxyl, C 1-6 alkyl or —OC 1-6 alkyl;
  • Each R 13 is independently hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, or 3-10 membered heterocycloalkyl;
  • Each R 14 is independently hydrogen or C 1-6 alkyl
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • the present invention provides a compound represented by formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof:
  • X is CR X or N
  • RX is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N( R6 ) 2 , C1-6 alkyl, -OC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, or C1-6 alkyl substituted by one or more halogens;
  • each R 6 is independently hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 6a , C 3-8 cycloalkyl substituted by one or more R 6b , 3-10 membered heterocycloalkyl substituted by one or more R 6c , C 6-10 aryl substituted by one or more R 6d , or 5-10 membered heteroaryl substituted by one or more R 6e ;
  • R 6 or two R 6 together with the nitrogen atom to which they are commonly attached form a 3-10 membered heterocyclic hydrocarbon group or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 6f ;
  • R 6a , R 6b , R 6c , R 6d , R 6e and R 6f is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • R 1 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N(R 6 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, -C(O)N(R 6 ) 2 , -C(O)R 6 , -C(O)OR 6 , -SO 2 R 6 , -SO 2 N(R 6 ) 2 , C 1-6 alkyl substituted by one or more R 1a , -OC 1-6 alkyl substituted by one or more R 1b , C 2-6 alkenyl substituted by one or more R 1c , C 2-6 alkynyl substituted by one or more R 1d , C 3-8 cycloalkyl substituted by one or more R 1e
  • R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , R 1g and R 1h is independently deuterium, halogen, cyano, hydroxyl, -N(R 6 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 1-a , -OC 1-6 alkyl substituted by one or more R 1-b , C 2-6 alkenyl substituted by one or more R 1-c , C 2-6 alkynyl substituted by one or more R 1-d , C 3-8 cycloalkyl substituted by one or more R 1-e , 1-f substituted 3-10 membered heterocyclic hydrocarbon group, C 6-10 aryl group
  • R 1-a , R 1-b , R 1-c , R 1-d , R 1-e , R 1-f , R 1-g and R 1-h is independently deuterium, halogen, cyano, —NH 2 , hydroxyl, C 1-6 alkyl or —OC 1-6 alkyl;
  • Ring A is a C 3-8 cycloalkyl, a 3-10 membered heterocycloalkyl, a C 6-10 aryl or a 5-10 membered heteroaryl;
  • each R2 is independently halogen, cyano, C1-6 alkyl, -OC1-6 alkyl, -SC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, nitro, -N( R8 ) 2 , -S(O) 2 ( R8 ), -S(O) 2N ( R8 ) 2 , -S(O)( R8 ), -S(O)N( R8 ) 2 , -C(O)( R8 ), -C(O)O( R8 ), -C(O)O( R8 ), -C(O)N( R8 ) 2 , -OC(O)( R8 ), -OC(O)N( R8 ) 2 , -N( R8 )C(O)O( R8 ), -N( R8 )C(O)O( R8 ), -N( R8 )C(O)( R8 ), -N( R
  • Each R 2a is independently deuterium, halogen, cyano, -N(R 2-a ) 2 , hydroxy, C 1-6 alkyl or -OC 1-6 alkyl;
  • Each R 2-a is independently hydrogen or C 1-6 alkyl
  • n 0, 1, 2, 3, 4 or 5;
  • Each R 8 is independently hydrogen, C 1-6 alkyl, or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • Ring B is a C 3-8 cycloalkylene group, a 3-10 membered heterocycloalkylene group, a C 6-10 arylene group, or a 5-10 membered heteroarylene group;
  • each R3 is independently deuterium, halogen, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, nitro, -O( R6 ), -S( R6 ), -N( R6 )2, -S(O) 2 ( R6 ), -S(O) 2N ( R6 ) 2 , -S(O) ( R6 ), -S(O)N( R6 ) 2 , -C(O)(R6), -C(O)O( R6 ), -C(O)N( R6 ) 2 , -OC(O)( R6 ), -OC(O)N( R6 ) 2 , -N( R6 )C(O)O( R6 ) , -N(R6)C(O)( R6 ), -N( R6 )C(O)O( R6 ) 2 , -N(R6)C(O)( R6
  • Each R 3a is independently deuterium, halogen, cyano, -N(R 6 ) 2 , hydroxy, C 1-6 alkyl or -OC 1-6 alkyl;
  • n 0, 1, 2, 3 or 4;
  • L is a covalent bond, C 1-6 alkylene, -N( RL )-, -N( RL )C(O)-, -C(O)N( RL )-, -N( RL )S(O) 2- , -S(O)2N( RL )-, -O-, -C(O)-, -OC(O)-, -C(O )O-, -S-, -S(O)-, or -S(O)2- ;
  • each RL is independently hydrogen, C1-6 alkyl, C3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C1-6 alkyl substituted by one or more RL , C3-8 cycloalkyl substituted by one or more RLb , 3-10 membered heterocycloalkyl substituted by one or more RLc , C6-10 aryl substituted by one or more RLd , or 5-10 membered heteroaryl substituted by one or more RLe ;
  • R La , R Lb , R Lc , R Ld and R Le is independently deuterium, halogen, cyano, -NH 2 , hydroxyl, C 1-6 alkyl or -OC 1-6 alkyl;
  • R7 is halogen, cyano,
  • R 7a , R 7b and R 7c are each independently hydrogen, deuterium, halogen, cyano, —C(O)(R 6 ), —C(O)O(R 6 ), —C(O)N(R 6 ) 2 , C 1-6 alkyl, C 1-6 alkyl substituted by one or more R 7-a , C 2-6 alkenyl, C 2-6 alkenyl substituted by one or more R 7-b, C 2-6 alkynyl, C 2-6 alkynyl substituted by one or more R 7-c, C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 7-d , 3-10 membered heterocycloalkyl , 3-10 membered heterocycloalkyl substituted by one or more R 7-e , C 6-10 aryl, C 6-10 aryl substituted by one or more R 7-f , 5-10 membered heteroaryl, or substituted by one or more
  • R 7-a , R 7-b , R 7-c , R 7-d , R 7-e , R 7-f and R 7-g is independently deuterium, halogen, cyano, -N(R 6 ) 2 , hydroxyl, C 1- 6 alkyl or -OC 1-6 alkyl;
  • R 4 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -N(R 6 ) 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 4a , C 2-6 alkenyl substituted by one or more R 4b , C 2-6 alkynyl substituted by one or more R 4c , C 3-8 cycloalkyl substituted by one or more R 4d , 3-10 membered heterocycloalkyl substituted by one or more R 4e , C 6-10 aryl substituted by one or more R 4f , or 5-10 membered heteroaryl substituted by one or more R 4g ;
  • each of R 4a , R 4b , R 4c , R 4d , R 4e , R 4f and R 4g is independently deuterium, halogen, cyano, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, nitro, -O(R 6 ), -S(R 6 ), -N(R 6 ) 2 , -S(O) 2 (R 6 ) , -S(O) 2 N(R 6 ) 2 , -S(O)(R 6 ), -S(O)N(R 6 ) 2 , -C(O)(R 6 ), -C(O)O(R 6 ), -C(O)O(R 6 ), -C(O)N(R 6 ) 2 , -OC(O)(R 6 ), -OC(O)N(R 6 ) 2 , -N(R 6 )C(O)O(R 6 ), -
  • R5 is hydrogen, deuterium, halogen, hydroxyl, cyano, nitro, -NR9R10 , -S( R9 ), -S(O) 2 ( R11 ), -S(O) 2N ( R9 ) 2 , -S(O)( R11 ), -S(O)N( R9 ) 2 , -C(O)( R11 ), -C(O)O( R9 ), -C (O)N( R9 ) 2 , -OC(O)( R9 ), -OC(O)N( R9 ) 2 , -N( R9 )C(O)O( R9 ), -N( R9)C(O)(R9), -N(R9 ) C (O)N( R9 ) 2 , -N( R9 )S(O) 2N ( R9 ) 2 , -N(R 9 )S(O) 2 (R 9 ), C 1-6
  • each of R 5a , R 5b , R 5c , R 5d , R 5e , R 5f , R 5g and R 5h is independently deuterium, halogen, hydroxy, cyano, nitro, -NR 9 R 10 , -S(R 9 ), -S(O) 2 (R 11 ), -S(O) 2 N(R 9 ) 2 , -S(O)(R 11 ), -S(O)N(R 9 ) 2 , -C(O)(R 11 ), -C(O)O(R 9 ), -C(O)N(R 9 ) 2 , -OC(O)(R 9 ), -OC(O)N(R 9 ) 2 , -N(R 9 )C(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -N(R 9 )C(O)O(R 9 ), -N(R 9
  • Each R 15 is independently C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 15a , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted by one or more R 15b ;
  • R 15a and R 15b are independently deuterium, halogen, cyano, hydroxy, -NH 2 , C 1-6 alkyl or -OC 1-6 alkyl;
  • each of R 5-a , R 5-b , R 5-c , R 5-d , R 5-e , R 5-f , R 5-g and R 5-h is independently deuterium, halogen, cyano, hydroxyl, oxo ( ⁇ O), —N(R 12 ) 2 , C 1-6 alkyl, —OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 5-a-1 , —OC 1-6 alkyl substituted by one or more R 5-a-2 , C 3-8 cycloalkyl substituted by one or more R 5-a-3 , or 3-12 membered heterocycloalkyl substituted by one or more R 5-a-4 ;
  • R 5-a-1 , R 5-a-2 , R 5-a-3 and R 5-a-4 is independently deuterium, halogen, cyano, hydroxyl or -N(R 12 ) 2 ;
  • Each R 12 is independently hydrogen or C 1-6 alkyl
  • each R 9 and R 10 is independently hydrogen, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 9a , C 3-8 cycloalkyl substituted by one or more R 9b , 3-12 membered heterocycloalkyl substituted by one or more R 9c , C 6-10 aryl substituted by one or more R 9d , or 5-10 membered heteroaryl substituted by one or more R 9e ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • each of R 9a , R 9b , R 9c , R 9d , R 9e and R 9f is independently deuterium, halogen, cyano, -N(R 14 ) 2 , hydroxy, oxo, C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted by one or more R 9-a , -OC 1-6 alkyl substituted by one or more R 9-b , 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 9-c , C 3-8 cycloalkyl, or C 3-8 cycloalkyl substituted by one or more R 9-d ;
  • R 9-a , R 9-b , R 9-c and R 9-d is independently deuterium, hydroxyl, halogen, cyano or -NH 2 ;
  • each R 11 is independently hydrogen, halogen, hydroxy, C 1-6 alkyl, C 3-8 cycloalkyl, 3-10 membered heterocycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, C 1-6 alkyl substituted by one or more R 11a , C 3-8 cycloalkyl substituted by one or more R 11b , 3-10 membered heterocycloalkyl substituted by one or more R 11c , C 6-10 aryl substituted by one or more R 11d , or 5-10 membered heteroaryl substituted by one or more R 11e ;
  • R 11a , R 11b , R 11c , R 11d and R 11e is independently deuterium, halogen, cyano, —NH 2 , hydroxyl, C 1-6 alkyl or —OC 1-6 alkyl;
  • Each R 13 is independently hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, or 3-10 membered heterocycloalkyl;
  • Each R 14 is independently hydrogen or C 1-6 alkyl
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • each C 6-10 aryl group may independently be phenyl or naphthyl, for example phenyl.
  • each C 6-10 arylene group can be independently phenylene or naphthylene, for example phenylene, for example
  • each halogen can independently be fluorine, chlorine, bromine or iodine, such as fluorine or chlorine, and also such as fluorine.
  • each C 1-6 alkyl group may independently be C 1-4 alkyl group, and may be methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl or sec-butyl, for example, methyl, ethyl, isopropyl or isobutyl.
  • each -OC 1-6 alkyl group may independently be -OC 1-4 alkyl, and may be -O-methyl, -O-ethyl, -O-n-propyl, -O-isopropyl, -O-n-butyl, -O-tert-butyl, -O-isobutyl or -O-sec-butyl, for example -O-methyl, -O-ethyl or -O-isobutyl, and for example -O-methyl.
  • each 3-12 membered heterocyclic hydrocarbon group may independently be a 3-10 membered heterocyclic hydrocarbon group, and the 3-10 membered heterocyclic hydrocarbon group may be a 3-10 membered heterocyclic alkyl group or a 3-10 membered heterocyclic alkenyl group;
  • the 3-10 membered heterocycloalkyl group may be a 3-6 membered monocyclic heterocycloalkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocycloalkyl group, wherein the heteroatom species is one or both of N and O, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further Steps
  • the 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycloalkenyl group or a 6-10 membered polycyclic (eg, fused, spiro or bridged) heterocycloalkenyl group, wherein the heteroatom species is one or both of N and O and the number of heteroatoms is 1, 2 or 3.
  • each 3-12 membered heterocyclic hydrocarbon group may independently be a 3-10 membered heterocyclic hydrocarbon group, and the 3-10 membered heterocyclic hydrocarbon group may be a 3-10 membered heterocyclic alkyl group or a 3-10 membered heterocyclic alkenyl group;
  • the 3-10 membered heterocycloalkyl group may be a 3-6 membered monocyclic heterocycloalkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocycloalkyl group, wherein the heteroatom species is one or both of N and O, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example
  • the 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycloalkenyl group or a 6-10 membered polycyclic (eg, fused, spiro or bridged) heterocycloalkenyl group, wherein the heteroatom species is one or both of N and O and the number of heteroatoms is 1, 2 or 3.
  • each 3-10 membered heterocycloalkyl group can independently be a 3-10 membered heterocycloalkyl group or a 3-10 membered heterocycloalkenyl group;
  • the 3-10 membered heterocycloalkyl group may be a 3-6 membered monocyclic heterocycloalkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocycloalkyl group, wherein the heteroatom species is one or both of N and O, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example
  • the 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycloalkenyl group or a 6-10 membered polycyclic (eg, fused, spiro or bridged) heterocycloalkenyl group, wherein the heteroatom species is one or both of N and O and the number of heteroatoms is 1, 2 or 3.
  • each 3-12 membered heterocyclic hydrocarbon group can be independently a 3-10 membered heterocyclic hydrocarbon group, and the 3-10 membered heterocyclic hydrocarbon group can be a 3- 10-membered heterocycloalkyl or 3-10-membered heterocycloalkenyl;
  • the 3-10 membered heterocycloalkyl group may be a 3-6 membered monocyclic heterocycloalkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocycloalkyl group, wherein the heteroatom species is one, two or more of N, O or S, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example
  • the 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycloalkenyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic, or bridged) heterocycloalkenyl group, wherein the heteroatom species is one, two or more of N, O, or S, and the number of heteroatoms is 1, 2, or 3.
  • each 3-10 membered heterocycloalkyl group can independently be a 3-10 membered heterocycloalkyl group or a 3-10 membered heterocycloalkenyl group;
  • the 3-10 membered heterocycloalkyl group may be a 3-6 membered monocyclic heterocycloalkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocycloalkyl group, wherein the heteroatom species is one, two or more of N, O or S, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example
  • the 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycloalkenyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic, or bridged) heterocycloalkenyl group, wherein the heteroatom species is one, two or more of N, O, or S, and the number of heteroatoms is 1, 2, or 3.
  • each 3-12 membered heterocyclic hydrocarbon group may independently be a 3-10 membered heterocyclic hydrocarbon group, and the 3-10 membered heterocyclic hydrocarbon group may be a 3-10 membered heterocyclic alkyl group or a 3-10 membered heterocyclic alkenyl group;
  • the 3-10 membered heterocycloalkyl group may be a 3-6 membered monocyclic heterocycloalkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocycloalkyl group, wherein the heteroatom species is one, two or more of N, O or S, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example
  • the 3-10 membered heterocycloalkenyl group may be a heteroatom selected from the group consisting of one, two or more heteroatoms selected from the group consisting of N, O or S, and the number of heteroatoms selected from the group consisting of 1 3-6 membered monocyclic heterocycloalkenyl or 6-10 membered polycyclic (eg, fused, spiro or bridged) heterocycloalkenyl, for example Further example
  • each 3-10 membered heterocycloalkyl group can independently be a 3-10 membered heterocycloalkyl group or a 3-10 membered heterocycloalkenyl group;
  • the 3-10 membered heterocycloalkyl group may be a 3-6 membered monocyclic heterocycloalkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocycloalkyl group, wherein the heteroatom species is one, two or more of N, O or S, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example
  • the 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycloalkenyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocycloalkenyl group, wherein the heteroatom species is one, two or more of N, O or S, and the number of heteroatoms is 1, 2, 3 or 4. Further example,
  • each 3-10 membered heterocyclic hydrocarbon group can be independently a 3-10 membered heterocyclic alkyl group or a 3-10 membered heterocyclic alkenyl group
  • the 3-10 membered heterocyclic alkyl group can be a 3-6 membered monocyclic heterocyclic alkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocyclic alkyl group, wherein the heteroatom species is one or both of N and O, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, base, Another example Further example Further example
  • the 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycloalkenyl group or a 6-10 membered polycyclic (eg, fused, spiro or bridged) heterocycloalkenyl group, wherein the heteroatom
  • each 3-10 membered heterocyclic hydrocarbon group can be independently a 3-10 membered heterocyclic alkyl group or a 3-10 membered heterocyclic alkenyl group
  • the 3-10 membered heterocyclic alkyl group can be a 3-6 membered monocyclic heterocyclic alkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocyclic alkyl group, wherein the heteroatom species is one or both of N and O, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example Further example Further example
  • the 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycloalkenyl group or a 6-10 membered polycyclic (eg, fused, spiro or bridged) heterocycloalkenyl group, wherein the heteroatom species is
  • each 3-10 membered heterocyclic hydrocarbon group in R 7b , R 7c , R 7-a and R 11 may independently be a 3-10 membered heterocyclic alkyl group or a 3-10 membered heterocyclic alkenyl group
  • the 3-10 membered heterocyclic alkyl group may be a 3-6 membered monocyclic heterocyclic alkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocyclic alkyl group, wherein the heteroatom species is one or both of N and O, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example Further example Further example Further example
  • the 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycloalkenyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged)
  • each 3-12 membered heterocyclic hydrocarbon group may independently be a 3-10 membered heterocyclic hydrocarbon group
  • the 3-10 membered heterocyclic hydrocarbon group may be a 3-10 membered heterocyclic alkyl group or a 3-10 membered heterocyclic alkenyl group
  • the 3-10 membered heterocyclic alkyl group may be a 3-6 membered monocyclic heterocyclic alkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocyclic alkyl group, wherein the heteroatom species is one or both of N and O, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example Further example The 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycl
  • each 3-12 membered heterocyclic hydrocarbon group may independently be a 3-10 membered heterocyclic hydrocarbon group
  • the 3-10 membered heterocyclic hydrocarbon group may be a 3-10 membered heterocyclic alkyl group or a 3-10 membered heterocyclic alkenyl group
  • the 3-10 membered heterocyclic alkyl group may be a 3-6 membered monocyclic heterocyclic alkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocyclic alkyl group, wherein the heteroatom species is one or both of N and O, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example Further example The 3-10 membered heterocycloalkenyl group may be a 3-6 membered monocyclic heterocycl
  • each 3-12 membered heterocyclic hydrocarbon group may independently be a 3-10 membered heterocyclic hydrocarbon group
  • the 3-10 membered heterocyclic hydrocarbon group may be a 3-10 membered heterocyclic alkyl group or a 3-10 membered heterocyclic alkenyl group
  • the 3-10 membered heterocyclic alkyl group may be a 3-6 membered monocyclic heterocyclic alkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocyclic alkyl group, wherein the heteroatom species is one, two or more of N, O or S, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example Further example The 3-10 membered heterocycloalkenyl group may be a 3-6 membered mono
  • each 3-12 membered heterocyclic hydrocarbon group may independently be a 3-10 membered heterocyclic hydrocarbon group
  • the 3-10 membered heterocyclic hydrocarbon group may be a 3-10 membered heterocyclic alkyl group or a 3-10 membered heterocyclic alkenyl group
  • the 3-10 membered heterocyclic alkyl group may be a 3-6 membered monocyclic heterocyclic alkyl group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocyclic alkyl group, wherein the heteroatom species is one, two or more of N, O or S, and the number of heteroatoms is 1, 2 or 3, such as piperazinyl, piperidinyl, Another example Further example The 3-10 membered heterocycloalkenyl group
  • each C 3-8 cycloalkyl group may independently be a C 3-8 cycloalkyl group or a C 3-8 cycloalkenyl group, for example, a C 3-8 cycloalkyl group;
  • the C 3-8 cycloalkyl group may be a C 3-8 monocyclic cycloalkyl group or a C 6-8 polycyclic (for example, a cyclic, spirocyclic or bridged) cycloalkyl group, preferably a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl group, for example, a cyclopropyl group
  • the C 3-8 cycloalkenyl group may be a C 3-8 monocyclic cycloalkenyl group or a C 6-8 polycyclic (for example, a cyclic, spirocyclic or bridged) cycloalkenyl group.
  • each C 1-6 alkylene group can independently be methylene, ethylene, n-propylene, isopropylene, n-butylene, tert-butylene, isobutylene or sec-butylene, preferably methylene.
  • each C 2-6 alkenyl group can independently be ethenyl, propenyl, butenyl or pentenyl.
  • each C2-6 alkynyl group can independently be ethynyl, propynyl, butynyl or pentynyl, for example
  • each 5-10 membered heteroaryl group can independently be a 5-6 membered monocyclic heteroaryl group or an 8-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heteroaryl group, wherein the heteroatom species is N and the number of heteroatoms is 1, 2 or 3, such as pyridyl,
  • each 5-10 membered heteroarylene group can independently be a 5-6 membered monocyclic heteroarylene group or an 8-10 membered polycyclic (eg, fused, spiro or bridged) heteroarylene group, wherein the heteroatom species is N and the number of heteroatoms is 1, 2 or 3.
  • each C 3-8 cycloalkylene group may independently be a C 3-8 cycloalkylene group or a C 3-8 cycloalkenylene group
  • the C 3-8 cycloalkylene group may be a C 3-8 monocyclic cycloalkylene group or a C 6-8 polycyclic (e.g., cyclic, spirocyclic or bridged) cycloalkylene group
  • the C 3-8 cycloalkenylene group may be a C 3-8 monocyclic cycloalkenylene group or a C 6-8 polycyclic (e.g., cyclic, spirocyclic or bridged) cycloalkenylene group.
  • each 3-10 membered heterocycloalkylene group may independently be a 3-10 membered heterocycloalkylene group or a 3-10 membered heterocycloalkenylene group, wherein the 3-10 membered heterocycloalkylene group may be a 3-6 membered monocyclic heterocycloalkylene group or a 6-10 membered polycyclic (e.g., cyclic, spirocyclic or bridged) heterocycloalkylene group, wherein the heteroatom species is one or both of N and O, and the number of heteroatoms is 1, 2 or 3.
  • the alkenyl group may be a 3-6 membered monocyclic heterocycloalkenylene group or a 6-10 membered polycyclic (eg, fused, spiro or bridged) heterocycloalkenylene group, wherein the heteroatom species is one or both of N and O and the number of heteroatoms is 1, 2 or 3.
  • each -S- C1-6 alkyl group may independently be -S-C1-4 alkyl group, and may be methylmercapto, ethylmercapto, n-propylmercapto, isopropylmercapto, n-butylmercapto, isobutylmercapto, sec-butylmercapto or tert-butylmercapto.
  • X is CR X .
  • RX is hydrogen
  • R 1 is -N(R 6 ) 2 .
  • each R 6 is independently hydrogen.
  • Ring A is C 6-10 aryl or 5-10 membered heteroaryl, preferably C 6-10 aryl.
  • each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -N(R 8 ) 2 , -S(O) 2 (R 8 ) or -C(O)N(R 8 ) 2 , preferably halogen, -OC 1-6 alkyl or -C(O)N(R 8 ) 2 , more preferably -OC 1-6 alkyl or -C(O)N(R 8 ) 2 .
  • each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl , -N(R 8 ) 2 , -S(O) 2 (R 8 ) or -C(O)N(R 8 ) 2 , wherein the C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ; preferably, each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkynyl or -C(O)N(R 8 ) 2 , wherein the C 1-6 alkyl, -OC 1-6 alkyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ; more preferably
  • each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl , -N(R 8 ) 2 , -S(O) 2 (R 8 ) or -C(O)N(R 8 ) 2 , wherein the C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ; preferably, each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkynyl, -N(R 8 ) 2 or -C(O)N(R 8 ) 2 , wherein the C 1-6 alkyl , -OC 1-6 alkyl and C 2-6 alkynyl are each independently unsubstituted or substituted by
  • m is 1, 2 or 3, preferably 2.
  • m is 1, 2 or 3, preferably 2 or 3, more preferably 2.
  • each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a .
  • each R 8 is independently hydrogen, C 1-6 alkyl or C 1-6 alkyl substituted by one or more R 8a ; preferably, each R 8 is independently hydrogen or C 1-6 alkyl substituted by one or more R 8a .
  • each R 8a is independently deuterium, halogen or hydroxy; preferably, each R 8a is independently deuterium or halogen.
  • each R 8 is independently hydrogen, C 1-6 alkyl, C 1-6 alkyl substituted by one or more R 8a , or C 3-8 cycloalkyl substituted by one or more R 8b ; preferably, each R 8 is independently hydrogen, C 1-6 alkyl substituted by one or more R 8a , or C 3-8 cycloalkyl substituted by one or more R 8b .
  • each R 8a and R 8b are independently deuterium, halogen, hydroxyl, C 1-6 alkane substituted with one or more R 8-a. preferably, each R 8a is independently deuterium, halogen, C 1-6 alkyl substituted by one or more R 8-a , or C 3-8 cycloalkyl substituted by one or more R 8 -b , and each R 8b is independently halogen or C 1-6 alkyl substituted by one or more R 8-a .
  • each of R 8-a and R 8-b is halogen.
  • each R 8a is independently halogen or hydroxy, preferably halogen.
  • each R 2a is independently deuterium, halogen or hydroxy, preferably deuterium or halogen, more preferably deuterium.
  • Ring B is a C 6-10 arylene group or a 5-10 membered heteroarylene group, preferably a C 6-10 arylene group.
  • R 3 is halogen or C 1-6 alkyl.
  • n 0, 1 or 2, preferably 0.
  • n is 0 or 1.
  • L is -N( RL )C(O)-.
  • RL is hydrogen or C1-6 alkyl, preferably hydrogen.
  • R7 is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl
  • R 7a is hydrogen, halogen or C 1-6 alkyl, preferably halogen.
  • R 7b is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocycloalkyl or 3-10 membered heterocycloalkyl substituted by one or more R 7-e , preferably hydrogen or 3-10 membered heterocycloalkyl substituted by one or more R 7-e , more preferably hydrogen.
  • R 7b is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocycloalkyl substituted by one or more R 7-e , preferably R 7b is hydrogen, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocycloalkyl substituted by one or more R 7-e .
  • R 7c is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocycloalkyl or 3-10 membered heterocycloalkyl substituted by one or more R 7-e , preferably hydrogen or 3-10 membered heterocycloalkyl substituted by one or more R 7-e , more preferably hydrogen.
  • R 7c is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocycloalkyl substituted by one or more R 7-e , preferably R 7c is hydrogen, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocycloalkyl substituted by one or more R 7-e .
  • each R 7-e is independently halogen, hydroxy or C 1-6 alkyl, preferably C 1-6 alkyl.
  • each R 7-a and R 7-e is independently halogen, hydroxy, C 1-6 alkyl or 3-10 membered heterocyclic hydrocarbon group, preferably each R 7-a and R 7-e is independently C 1-6 alkyl or 3-10 membered heterocyclic hydrocarbon group.
  • each R 7-a and R 7-e is independently halogen, hydroxyl or C 1-6 alkyl; preferably, each R 7-a and R 7-e is independently C 1-6 alkyl.
  • R 4 is C 1-6 alkyl or C 1-6 alkyl substituted by one or more R 4a , preferably C 1-6 alkyl.
  • each R 4a is independently halogen or cyano.
  • R 5 is C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 5e, 3-12 membered heterocycloalkyl or 3-12 membered heterocycloalkyl substituted by one or more R 5f, preferably C 1-6 alkyl substituted by one or more R 5a, C 3-8 cycloalkyl substituted by one or more R 5e ...12 membered heterocycloalkyl or 3-12 membered heterocycloalkyl substituted by one or more R 5f .
  • R 5 is C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ; preferably C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ; more preferably C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , or 3-12 membered heterocycloalkyl substituted by one or more R 5f .
  • R 5 is -C(O)(R 11 ), -P(O)(R 18 ) 2 , C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ; for example, R 5 is -C(O)(R 11 ), -C(O)N(R 9 ) 2 , -P(O)(R 18 ) 2 , C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , or 3-12 membered heterocycloalkyl substituted by one or more R 5f ; for another example, R 5 is -C(O)(R 11 ), -
  • R 5 is -C(O)(R 11 ), -C(O)N(R 9 ) 2 , -P(O)(R 18 ) 2 , 3-12-membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , or 3-12-membered heterocycloalkyl substituted by one or more R 5f ; for example, R 5 is -C(O)(R 11 ), -C(O)N(R 9 ) 2 , 3-12-membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , or 3-12-membered heterocycloalkyl substituted by one or more R 5f .
  • each R 5a is independently halogen, hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted by one or more R 5-b , or 3-12 membered heterocycloalkyl substituted by one or more R 5-f , preferably hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted by one or more R 5-b , or 3-12 membered heterocycloalkyl substituted by one or more R 5-f , more preferably -NR 9 R 10 or 3-12 membered heterocycloalkyl.
  • each R 5a is independently halogen, hydroxyl, -NR 9 R 10 , -S(O) 2 (R 11 ), -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted by one or more R 5-b , or 3-12 membered heterocycloalkyl substituted by one or more R 5-f ; preferably hydroxyl, -NR 9 R 10 , -S(O) 2 (R 11 ), -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted by one or more R 5-b , or 3-12 membered heterocycloalkyl substituted by one or more R 5-f ; more preferably hydroxyl, -NR 9 R 10 , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted by one or more R 5- f .
  • each R 5a is independently hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), C 1-6 alkyl, -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted by one or more R 5-b , or 3-12 membered heterocycloalkyl substituted by one or more R 5-f ; preferably, each R 5a is independently hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), C 1-6 alkyl, -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted by one or more R 5-f .
  • the 3-12 membered heterocycloalkyl is preferably a 3-6 membered monocyclic heterocycloalkyl or a 6-10 membered polycyclic heterocycloalkyl (eg, a bridged ring).
  • R 5a is a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 5-f
  • the heteroatoms in the 3-12 membered heterocyclic hydrocarbon group are selected from one or both of N and O, and the number of heteroatoms is 1 or 2.
  • R 5a is a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 5-f , and at least one heteroatom in the 3-12 membered heterocyclic hydrocarbon group is N
  • the 3-12 membered heterocyclic hydrocarbon group is preferably connected to the C 1-6 alkyl group in R 5 through N.
  • each R 5-b is independently halogen, hydroxy or -OC 1-6 alkyl, preferably hydroxy or -OC 1-6 alkyl.
  • each R 5-b is independently halogen, hydroxyl, -OC 1-6 alkyl, 3-12-membered heterocyclic hydrocarbon group or 3-12-membered heterocyclic hydrocarbon group substituted by one or more R 5-a-4 ; preferably, each R 5-b is independently halogen, hydroxyl, -OC 1-6 alkyl or 3-12-membered heterocyclic hydrocarbon group; more preferably, each R 5-b is independently hydroxyl or -OC 1-6 alkyl.
  • each R 5-a-4 is C 1-6 alkyl.
  • each R 15 is independently C 3-8 cycloalkyl or 3-12 membered heterocycloalkyl, preferably 3-12 membered heterocycloalkyl.
  • each R 15 is independently C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted with one or more R 15b .
  • each R 15b is independently halogen or C 1-6 alkyl.
  • each R 5-f is independently halogen, hydroxyl, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 5-a-1 , preferably halogen, hydroxyl, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 5-a-1 .
  • each R 5-f is independently halogen, hydroxyl, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 5-a-1 , preferably halogen, hydroxyl, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 5-a-1 , more preferably halogen, hydroxyl or C 1-6 alkyl.
  • each R 5-f is independently halogen, hydroxy, oxo, -N(R 12 ) 2 , C 1-6 alkyl, 3-12 membered heterocyclic hydrocarbon group or C 1-6 alkyl substituted by one or more R 5-a-1 , preferably halogen, hydroxy, -N(R 12 ) 2 or C 1-6 alkyl.
  • each R 5-a-1 is independently halogen or hydroxy, preferably hydroxy.
  • each R 5e is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 , preferably -NR 9 R 10 .
  • each R 5e is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 , preferably halogen or -NR 9 R 10 , more preferably -NR 9 R 10 .
  • each R 5f is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 , preferably hydroxy or -NR 9 R 10 , more preferably -NR 9 R 10 .
  • each R 5f is hydroxy, C 1-6 alkyl, -OC 1-6 alkyl, or -NR 9 R 10 .
  • each R 9 and R 10 is independently hydrogen, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 9a , preferably hydrogen or C 1-6 alkyl;
  • R9 and R10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R9f , preferably R9 and R10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group.
  • each R 9 and R 10 is independently hydrogen, hydroxyl, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 9a , or 3-12 membered heterocycloalkyl substituted by one or more R 9c ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • each R 9 and R 10 is independently hydrogen, hydroxy, 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted with one or more R 9c , or C 1-6 alkyl;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f .
  • each R 9 and R 10 is independently hydrogen, hydroxyl, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12-membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 9a , C 3-8 cycloalkyl substituted by one or more R 9b , or 3-12-membered heterocycloalkyl substituted by one or more R 9c ; preferably, each R 9 and R 10 is independently hydrogen, hydroxyl, C 1-6 alkyl, 3-12-membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 9a , or 3-12-membered heterocycloalkyl substituted by one or more R 9c ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f .
  • each R 9a is independently halogen or hydroxy, preferably hydroxy.
  • each R 9a is independently halogen, hydroxy, 3-12 membered heterocycloalkyl or -N(R 14 ) 2 .
  • each R 9a is independently halogen, hydroxy, -N(R 14 ) 2 , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted by one or more R 9-c ; preferably, each R 9a is independently -N(R 14 ) 2 , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted by one or more R 9-c .
  • each R 9-c is independently C 1-6 alkyl.
  • each R 9b is independently deuterium, halogen, cyano, -N(R 14 ) 2 , hydroxyl or C 1-6 alkyl.
  • each R 9c is independently C 1-6 alkyl.
  • each R 9f is independently halogen, hydroxyl, oxo, -N(R 14 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted by one or more R 9 -a , 3-12 membered heterocycloalkyl or C 3-8 cycloalkyl, preferably halogen, hydroxyl, oxo, -N(R 14 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted by one or more R 9-a , or 3-12 membered heterocycloalkyl.
  • each R 9f is independently halogen, hydroxyl, oxo, -N(R 14 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted by one or more R 9 -a , 3-12 membered heterocyclic hydrocarbon group or C 3-8 cyclic hydrocarbon group, preferably halogen, hydroxyl, oxo, -N(R 14 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted by one or more R 9-a or 3-12 membered heterocyclic hydrocarbon group, more preferably halogen, hydroxyl or C 1-6 alkyl.
  • each R 9f is independently halogen, -N(R 14 ) 2 , hydroxy, oxo( ⁇ O), C 1-6 alkyl, -S(O) 2 (R 19 ), C 1-6 alkyl substituted with one or more R 9-a , 3-12 membered heterocycloalkyl, or C 3-8 cycloalkyl.
  • each R 9-a is independently hydroxy, halogen or -NH 2 , preferably hydroxy.
  • each R 9-a is independently C 1-6 alkyl, hydroxyl, -S(O) 2 (R 17 ), halogen, -NHR 16 , -N(R 16 ) 2 or -NH 2 .
  • each R 9- a is independently C 1-6 alkyl, hydroxyl, -S (O) 2 (R 17 ) or -N(R 16 ) 2 .
  • each R 9-a is independently C 1-6 alkyl or hydroxyl.
  • each R 9-a is independently C 1-6 alkyl, hydroxyl, halogen, -S(O) 2 (R 17 ) or -N(R 16 ) 2 ; preferably, each R 9-a is independently hydroxyl, halogen, -S(O) 2 (R 17 ) or -N(R 16 ) 2 .
  • each R 11 is independently C 1-6 alkyl.
  • each R 11 is independently C 1-6 alkyl, 3-10 membered heterocycloalkyl, or 3-10 membered heterocycloalkyl substituted by one or more R 11c ; for example, each R 11 is independently 3-10 membered heterocycloalkyl or 3-10 membered heterocycloalkyl substituted by one or more R 11c .
  • each R 11c is independently -NH 2 , hydroxy or C 1-6 alkyl; for example, each R 11c is independently hydroxy or C 1-6 alkyl, for example C 1-6 alkyl.
  • each R 12 is independently hydrogen.
  • each R 12 is independently C 1-6 alkyl.
  • each R 13 is independently hydrogen or C 1-6 alkyl.
  • each R 14 is independently hydrogen.
  • each R 14 is independently C 1-6 alkyl.
  • each R 16 is independently C 1-6 alkyl.
  • each R 17 is independently C 1-6 alkyl.
  • each R 18 is independently C 1-6 alkyl.
  • each R 19 is independently C 1-6 alkyl.
  • the stereoisomer refers to a configurational isomer, a conformational isomer, or a mixture thereof, such as an enantiomer, a diastereomer, or a mixture thereof (eg, an enantiomer).
  • the compound as shown in formula (I) when the compound as shown in formula (I) contains a chiral center, the compound as shown in formula (I) is each stereoisomer or a mixture thereof.
  • the compound as shown in formula (I) when it contains one chiral center, is R configuration and/or S configuration.
  • X is CR X ;
  • RX is hydrogen
  • R 1 is -N(R 6 ) 2 ;
  • Each R 6 is independently hydrogen
  • Ring A is C 6-10 aryl or 5-10 membered heteroaryl
  • each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -N(R 8 ) 2 , -S(O) 2 (R 8 ) or -C(O)N(R 8 ) 2 ;
  • n 1, 2 or 3;
  • Each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently halogen or hydroxy
  • Ring B is a C 6-10 arylene group or a 5-10 membered heteroarylene group
  • n 0, 1 or 2;
  • L is -N( RL )C(O)-;
  • RL is hydrogen or C1-6 alkyl
  • R 7a is hydrogen, halogen or C 1-6 alkyl
  • R 7b is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocyclic hydrocarbon group or 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • R 7c is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocyclic hydrocarbon group or 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • Each R 7-e is independently halogen, hydroxy or C 1-6 alkyl
  • R 4 is C 1-6 alkyl or C 1-6 alkyl substituted by one or more R 4a ;
  • Each R 4a is independently halogen or cyano
  • R 5 is C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted by one or more R 5f ;
  • each R 5a is independently halogen, hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted with one or more R 5-b , or 3-12 membered heterocycloalkyl substituted with one or more R 5-f ;
  • Each R 5-b is independently halogen, hydroxy or -OC 1-6 alkyl
  • Each R 15 is independently a C 3-8 cycloalkyl or a 3-12 membered heterocycloalkyl
  • Each R 5-f is independently halogen, hydroxy, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 5-a-1 ;
  • Each R 5-a-1 is independently halogen or hydroxy
  • Each R 5e is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 ;
  • Each R 5f is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 ;
  • R 9 and R 10 is independently hydrogen, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 9a ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9a is independently halogen or hydroxy
  • Each R 9f is independently halogen, hydroxy, oxo, -N(R 14 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted with one or more R 9-a , 3-12 membered heterocycloalkyl or C 3-8 cycloalkyl;
  • Each R 9-a is independently hydroxy, halogen or -NH 2 ;
  • Each R 11 is independently C 1-6 alkyl
  • Each R 12 is independently hydrogen
  • Each R 13 is independently hydrogen or C 1-6 alkyl
  • Each R 14 is independently hydrogen.
  • the heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CR X ;
  • RX is hydrogen
  • R 1 is -N(R 6 ) 2 ;
  • Each R 6 is independently hydrogen
  • Ring A is C 6-10 aryl
  • Each R 2 is independently halogen, -OC 1-6 alkyl or -C(O)N(R 8 ) 2 ;
  • n 2;
  • Each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently halogen
  • Ring B is a C 6-10 arylene group
  • n 0;
  • L is -N( RL )C(O)-;
  • R 7a is hydrogen, halogen or C 1-6 alkyl
  • R 7b is hydrogen or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • R 7c is hydrogen or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • Each R 7-e is independently C 1-6 alkyl
  • R4 is C1-6 alkyl
  • R 5 is C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , or 3-12 membered heterocycloalkyl substituted by one or more R 5f ;
  • Each R 5a is independently hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted by one or more R 5-b , or 3-12 membered heterocycloalkyl substituted by one or more R 5-f ;
  • Each R 5-b is independently hydroxy or -OC 1-6 alkyl
  • Each R 15 is independently a 3-12 membered heterocyclic hydrocarbon group
  • Each R 5-f is independently halogen, hydroxy, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, 3-12 membered heterocyclic hydrocarbon group, or C 1-6 alkyl substituted by one or more R 5-a-1 ;
  • Each R 5-a-1 is independently hydroxyl
  • each R 5e is independently -NR 9 R 10 ;
  • Each R 5f is independently hydroxy or -NR 9 R 10 ;
  • R 9 and R 10 is independently hydrogen, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 9a ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9a is independently hydroxy
  • Each R 9f is independently halogen, hydroxy, oxo, -N(R 14 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted with one or more R 9 -a , or 3-12 membered heterocyclic hydrocarbon group;
  • Each R 9-a is independently hydroxy
  • Each R 11 is independently C 1-6 alkyl
  • Each R 12 is independently hydrogen
  • Each R 13 is independently hydrogen or C 1-6 alkyl
  • Each R 14 is independently hydrogen.
  • the heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CR X ;
  • RX is hydrogen
  • R 1 is -N(R 6 ) 2 ;
  • Each R 6 is independently hydrogen
  • Ring A is C 6-10 aryl
  • Each R 2 is independently -OC 1-6 alkyl or -C(O)N(R 8 ) 2 ;
  • n 2;
  • Each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently halogen (eg, fluorine);
  • Ring B is a C 6-10 arylene group
  • n 0;
  • L is -N( RL )C(O)-;
  • R 7a is halogen (e.g. fluorine);
  • R 7b is hydrogen
  • R 7c is hydrogen
  • R 4 is C 1-6 alkyl (e.g. methyl);
  • R 5 is a C 1-6 alkyl group substituted by one or more R 5a or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 5f ;
  • Each R 5a is independently -NR 9 R 10 or a 3-12 membered heterocyclic hydrocarbon group
  • each R 5f is independently -NR 9 R 10 ;
  • Each R 9 and R 10 is independently hydrogen or C 1-6 alkyl
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CR X ;
  • RX is hydrogen
  • R 1 is -N(R 6 ) 2 ;
  • Each R 6 is independently hydrogen
  • Ring A is C 6-10 aryl or 5-10 membered heteroaryl
  • each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -N(R 8 ) 2 , -S(O) 2 (R 8 ) or -C(O)N(R 8 ) 2 , wherein said C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ;
  • n 1, 2 or 3;
  • Each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently halogen or hydroxy
  • Each R 2a is independently deuterium, halogen or hydroxy
  • Ring B is a C 6-10 arylene group or a 5-10 membered heteroarylene group
  • n 0, 1 or 2;
  • L is -N( RL )C(O)-;
  • RL is hydrogen or C1-6 alkyl
  • R 7a is hydrogen, halogen or C 1-6 alkyl
  • R 7b is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocyclic hydrocarbon group or 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • R 7c is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocyclic hydrocarbon group or 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • Each R 7-e is independently halogen, hydroxy or C 1-6 alkyl
  • R 4 is C 1-6 alkyl or C 1-6 alkyl substituted by one or more R 4a ;
  • Each R 4a is independently halogen or cyano
  • R 5 is C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ;
  • each R 5a is independently halogen, hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted with one or more R 5-b , or 3-12 membered heterocycloalkyl substituted with one or more R 5-f ;
  • Each R 5-b is independently halogen, hydroxy or -OC 1-6 alkyl
  • Each R 15 is independently a C 3-8 cycloalkyl group or a 3-12 membered heterocycloalkyl group;
  • Each R 5-f is independently halogen, hydroxy, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 5-a-1 ;
  • Each R 5-a-1 is independently halogen or hydroxy
  • Each R 5e is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 ;
  • Each R 5f is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 ;
  • R 9 and R 10 is independently hydrogen, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 9a ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9a is independently halogen or hydroxy
  • Each R 9f is independently halogen, hydroxy, oxo, -N(R 14 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted with one or more R 9-a , 3-12 membered heterocycloalkyl or C 3-8 cycloalkyl;
  • Each R 9-a is independently hydroxy, halogen or -NH 2 ;
  • Each R 11 is independently C 1-6 alkyl
  • Each R 12 is independently hydrogen
  • Each R 13 is independently hydrogen or C 1-6 alkyl
  • Each R 14 is independently hydrogen.
  • the heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CR X ;
  • RX is hydrogen
  • R 1 is -N(R 6 ) 2 ;
  • Each R 6 is independently hydrogen
  • Ring A is C 6-10 aryl or 5-10 membered heteroaryl
  • each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -N(R 8 ) 2 , -S(O) 2 (R 8 ) or -C(O)N(R 8 ) 2 , wherein said C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ;
  • n 1, 2 or 3;
  • Each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently halogen or hydroxy
  • Each R 2a is independently deuterium, halogen or hydroxy
  • Ring B is a C 6-10 arylene group or a 5-10 membered heteroarylene group
  • n 0, 1 or 2;
  • L is -N( RL )C(O)-;
  • RL is hydrogen or C1-6 alkyl
  • R 7a is hydrogen, halogen or C 1-6 alkyl
  • R 7b is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocyclic hydrocarbon group or 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • R 7c is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocyclic hydrocarbon group or 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • Each R 7-e is independently halogen, hydroxy or C 1-6 alkyl
  • R 4 is C 1-6 alkyl or C 1-6 alkyl substituted by one or more R 4a ;
  • Each R 4a is independently halogen or cyano
  • R 5 is -C(O)(R 11 ), -P(O)(R 18 ) 2 , C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ;
  • each R 5a is independently halogen, hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted with one or more R 5-b , or 3-12 membered heterocycloalkyl substituted with one or more R 5-f ;
  • Each R 5-b is independently halogen, hydroxy or -OC 1-6 alkyl
  • Each R 15 is independently a C 3-8 cycloalkyl or a 3-12 membered heterocycloalkyl
  • Each R 5-f is independently halogen, hydroxyl, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered Heterocyclic hydrocarbon group or C 1-6 alkyl group substituted by one or more R 5-a-1 ;
  • Each R 5-a-1 is independently halogen or hydroxy
  • Each R 5e is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 ;
  • Each R 5f is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 ;
  • each R 9 and R 10 is independently hydrogen, hydroxy, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 9a , or 3-12 membered heterocycloalkyl substituted by one or more R 9c ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9a is independently halogen, hydroxy, 3-12 membered heterocyclic hydrocarbon group or -N(R 14 ) 2 ;
  • Each R 9c is independently C 1-6 alkyl
  • Each R 9f is independently halogen, hydroxy, oxo, -N(R 14 ) 2 , C 1-6 alkyl, -S(O) 2 (R 19 ), -OC 1-6 alkyl, C 1-6 alkyl substituted with one or more R 9-a , 3-12 membered heterocycloalkyl or C 3-8 cycloalkyl;
  • Each R 9-a is independently C 1-6 alkyl, hydroxy, -S(O) 2 (R 17 ), halogen, -NHR 16 , -N(R 16 ) 2 or -NH 2 ;
  • Each R 11 is independently a C 1-6 alkyl group, a 3-10 membered heterocyclic hydrocarbon group, or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 11c ;
  • Each R 11c is independently -NH 2 , hydroxyl or C 1-6 alkyl
  • Each R 12 is independently hydrogen
  • Each R 13 is independently hydrogen or C 1-6 alkyl
  • Each R 14 is independently hydrogen or C 1-6 alkyl
  • Each R 16 is independently C 1-6 alkyl
  • Each R 17 is independently C 1-6 alkyl
  • Each R 19 is independently C 1-6 alkyl
  • Each R 18 is independently a C 1-6 alkyl group.
  • the heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CR X ;
  • RX is hydrogen
  • R 1 is -N(R 6 ) 2 ;
  • Each R 6 is independently hydrogen
  • Ring A is C 6-10 aryl or 5-10 membered heteroaryl
  • each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkynyl or -C(O)N(R 8 ) 2 , wherein said C 1-6 alkyl, -OC 1-6 alkyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ;
  • n 2 or 3;
  • Each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently halogen
  • Each R 2a is independently deuterium or halogen
  • Ring B is a C 6-10 arylene group
  • n 0;
  • L is -N( RL )C(O)-;
  • R 7a is hydrogen, halogen or C 1-6 alkyl
  • R 7b is hydrogen or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • R 7c is hydrogen or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • Each R 7-e is independently C 1-6 alkyl
  • R4 is C1-6 alkyl
  • R 5 is C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ;
  • Each R 5a is independently hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted by one or more R 5-b , or 3-12 membered heterocycloalkyl substituted by one or more R 5-f ;
  • Each R 5-b is independently hydroxy or -OC 1-6 alkyl
  • Each R 15 is independently a 3-12 membered heterocyclic hydrocarbon group
  • Each R 5-f is independently halogen, hydroxy, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, 3-12 membered heterocyclic hydrocarbon group, or C 1-6 alkyl substituted by one or more R 5-a-1 ;
  • Each R 5-a-1 is independently hydroxyl
  • Each R 5e is independently halogen or -NR 9 R 10 ;
  • Each R 5f is independently hydroxy or -NR 9 R 10 ;
  • R 9 and R 10 is independently hydrogen, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 9a ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9a is independently hydroxy
  • Each R 9f is independently halogen, hydroxy, oxo, -N(R 14 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 1-6 alkyl substituted with one or more R 9 -a , or 3-12 membered heterocyclic hydrocarbon group;
  • Each R 9-a is independently hydroxy
  • Each R 11 is independently C 1-6 alkyl
  • Each R 12 is independently hydrogen
  • Each R 13 is independently hydrogen or C 1-6 alkyl
  • Each R 14 is independently hydrogen.
  • the heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CR X ;
  • RX is hydrogen
  • R 1 is -N(R 6 ) 2 ;
  • Each R 6 is independently hydrogen
  • Ring A is C 6-10 aryl or 5-10 membered heteroaryl
  • each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkynyl or -C(O)N(R 8 ) 2 , wherein said C 1-6 alkyl, -OC 1-6 alkyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ;
  • n 2 or 3;
  • Each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently halogen
  • Each R 2a is independently deuterium or halogen
  • Ring B is a C 6-10 arylene group
  • n 0;
  • L is -N( RL )C(O)-;
  • R 7a is hydrogen, halogen or C 1-6 alkyl
  • R 7b is hydrogen or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • R 7c is hydrogen or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • Each R 7-e is independently C 1-6 alkyl
  • R4 is C1-6 alkyl
  • R 5 is -C(O)(R 11 ), -P(O)(R 18 ) 2 , C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ;
  • Each R 5a is independently hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), -OR 15 , 3-12 membered heterocyclic hydrocarbon group, substituted by one or more R 5-b -OC 1-6 alkyl or 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 5-f ;
  • Each R 5-b is independently hydroxy or -OC 1-6 alkyl
  • Each R 15 is independently a 3-12 membered heterocyclic hydrocarbon group
  • Each R 5-f is independently halogen, hydroxy, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, 3-12 membered heterocyclic hydrocarbon group, or C 1-6 alkyl substituted by one or more R 5-a-1 ;
  • Each R 5-a-1 is independently hydroxyl
  • Each R 5e is independently halogen or -NR 9 R 10 ;
  • Each R 5f is independently hydroxy or -NR 9 R 10 ;
  • each R 9 and R 10 is independently hydrogen, hydroxy, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 9a , or 3-12 membered heterocycloalkyl substituted by one or more R 9c ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9a is independently halogen, hydroxy, 3-12 membered heterocyclic hydrocarbon group or -N(R 14 ) 2 ;
  • Each R 9c is independently C 1-6 alkyl
  • Each R 11 is independently a C 1-6 alkyl group, a 3-10 membered heterocyclic hydrocarbon group, or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 11c ;
  • Each R 11c is independently -NH 2 , hydroxyl or C 1-6 alkyl
  • Each R 12 is independently hydrogen
  • Each R 13 is independently hydrogen or C 1-6 alkyl
  • Each R 14 is independently hydrogen or C 1-6 alkyl
  • Each R 16 is independently C 1-6 alkyl
  • Each R 17 is independently C 1-6 alkyl
  • Each R 19 is independently C 1-6 alkyl
  • Each R 18 is independently a C 1-6 alkyl group.
  • the heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CR X ;
  • RX is hydrogen
  • Each R 6 is independently hydrogen
  • Ring A is C 6-10 aryl
  • Each R 2 is independently -OC 1-6 alkyl or -C(O)N(R 8 ) 2 ;
  • n 2;
  • Each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently halogen (eg, fluorine);
  • Ring B is a C 6-10 arylene group
  • n 0;
  • L is -N( RL )C(O)-;
  • R 7a is halogen (e.g. fluorine);
  • R 7b is hydrogen
  • R 7c is hydrogen
  • R 4 is C 1-6 alkyl (e.g. methyl);
  • R 5 is C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , or 3-12 membered heterocycloalkyl substituted by one or more R 5f ;
  • Each R 5a is independently hydroxy, -NR 9 R 10 , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted with one or more R 5-f ;
  • each R 5e is independently -NR 9 R 10 ;
  • each R 5f is independently -NR 9 R 10 ;
  • Each R 5-f is independently halogen, hydroxy or C 1-6 alkyl
  • Each R 9 and R 10 is independently hydrogen or C 1-6 alkyl
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9f is independently halogen, hydroxyl or C 1-6 alkyl.
  • the heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CR X ;
  • RX is hydrogen
  • R 1 is -N(R 6 ) 2 ;
  • Each R 6 is independently hydrogen
  • Ring A is C 6-10 aryl
  • Each R 2 is independently halogen, -OC 1-6 alkyl or -C(O)N(R 8 ) 2 ;
  • n 2;
  • Each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently halogen (eg, fluorine);
  • Ring B is a C 6-10 arylene group
  • n 0;
  • L is -N( RL )C(O)-;
  • R 7a is halogen (e.g. fluorine);
  • R 7b is hydrogen
  • R 7c is hydrogen
  • R 4 is C 1-6 alkyl (e.g. methyl);
  • R 5 is -C(O)(R 11 ), -C(O)N(R 9 ) 2 , C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , or 3-12 membered heterocycloalkyl substituted by one or more R 5f ;
  • Each R 5a is independently hydroxy, -NR 9 R 10 , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted with one or more R 5-f ;
  • each R 5e is independently -NR 9 R 10 ;
  • each R 5f is independently -NR 9 R 10 ;
  • Each R 5-f is independently halogen, hydroxy or C 1-6 alkyl
  • R 9 and R 10 is independently hydrogen, hydroxy, 3-12 membered heterocyclic hydrocarbon group, 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9c , or C 1-6 alkyl group;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9c is independently C 1-6 alkyl
  • Each R 9f is independently halogen, hydroxy, -N(R 14 ) 2 , C 3-8 cycloalkyl, oxo ( ⁇ O), C 1-6 alkyl, C 1-6 alkyl substituted with one or more R 9- a , or 3-12 membered heterocycloalkyl;
  • Each R 9-a is independently C 1-6 alkyl or hydroxyl
  • Each R 11 is independently a 3-10 membered heterocyclic hydrocarbon group or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 11c ;
  • Each R 11c is independently C 1-6 alkyl
  • Each R 14 is independently hydrogen or C 1-6 alkyl.
  • the heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CH
  • R1 is -NH2 ;
  • Ring A is C 6-10 aryl or 5-10 membered heteroaryl
  • each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -N(R 8 ) 2 , -S(O) 2 (R 8 ) or -C(O)N(R 8 ) 2 , wherein said C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ;
  • Each R 8 is independently hydrogen, C 1-6 alkyl, C 1-6 alkyl substituted by one or more R 8a , or C 3-8 cycloalkyl substituted by one or more R 8b ;
  • R 8a and R 8b are independently deuterium, halogen, hydroxyl, C 1-6 alkyl substituted by one or more R 8-a , or C 3-8 cycloalkyl substituted by one or more R 8-b ;
  • Each R 2a is independently deuterium or halogen
  • Ring B is a C 6-10 arylene group
  • R 3 is halogen or C 1-6 alkyl
  • R 7a is hydrogen, halogen or C 1-6 alkyl
  • R 7b is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocyclic hydrocarbon group, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • R 7c is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocyclic hydrocarbon group, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • R 7-a and R 7-e are independently halogen, hydroxy, C 1-6 alkyl or 3-10 membered heterocyclic hydrocarbon group;
  • R4 is C1-6 alkyl
  • R 5 is -C(O)(R 11 ), -P(O)(R 18 ) 2 , C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ;
  • Each R 5a is independently hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), C 1-6 alkyl, -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocyclic hydrocarbon group, -OC 1-6 alkyl substituted by one or more R 5-b or 3-12 membered heterocyclic hydrocarbon substituted by one or more R 5-f ;
  • Each R 5-b is independently halogen, hydroxy, -OC 1-6 alkyl, 3-12 membered heterocyclic hydrocarbon group, or 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 5-a-4 ;
  • Each R 5-a-4 is a C 1-6 alkyl group
  • Each R 15 is independently a C 3-8 cycloalkyl, a 3-12 membered heterocycloalkyl, or a 3-12 membered heterocycloalkyl substituted by one or more R 15b ;
  • Each R 15b is independently halogen or C 1-6 alkyl
  • Each R 5-f is independently halogen, hydroxy, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 5-a-1 ;
  • Each R 5-a-1 is halogen or hydroxy
  • Each R 5e is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 ;
  • Each R 5f is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 ;
  • each R 9 and R 10 is independently hydrogen, hydroxy, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 9a , C 3-8 cycloalkyl substituted by one or more R 9b , or 3-12 membered heterocycloalkyl substituted by one or more R 9c ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9a is independently halogen, hydroxy, -N(R 14 ) 2 , 3-12 membered heterocyclic hydrocarbon group, or 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9-c ;
  • Each R 9-c is independently C 1-6 alkyl
  • Each R 9b is independently deuterium, halogen, cyano, -N(R 14 ) 2 , hydroxyl or C 1-6 alkyl;
  • Each R 9c is independently C 1-6 alkyl
  • each R 9f is independently halogen, -N(R 14 ) 2 , hydroxy, oxo ( ⁇ O), C 1-6 alkyl, -S(O) 2 (R 19 ), C 1-6 alkyl substituted with one or more R 9- a , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl or C 3-8 cycloalkyl;
  • Each R 9-a is independently C 1-6 alkyl, hydroxy, halogen, -S(O) 2 (R 17 ), -NH 2 , -NH(R 16 ) or -N(R 16 ) 2 ;
  • Each R 11 is independently a C 1-6 alkyl group, a 3-10 membered heterocyclic hydrocarbon group, or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 11c ;
  • Each R 11c is independently hydroxy or C 1-6 alkyl
  • Each R 12 is independently hydrogen or C 1-6 alkyl
  • Each R 13 is independently hydrogen or C 1-6 alkyl
  • Each R 14 is independently hydrogen or C 1-6 alkyl
  • Each R 16 is independently C 1-6 alkyl
  • Each R 17 is independently C 1-6 alkyl
  • Each R 18 is independently C 1-6 alkyl
  • Each R 19 is independently C 1-6 alkyl
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2, 3 or 4;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CH
  • R1 is -NH2 ;
  • Ring A is C 6-10 aryl or 5-10 membered heteroaryl
  • each R 2 is independently halogen, -OC 1-6 alkyl or -C(O)N(R 8 ) 2 , wherein said -OC 1-6 alkyl is each independently unsubstituted or substituted with one or more R 2a ;
  • n 2 or 3;
  • Each R 8 is independently hydrogen, C 1-6 alkyl substituted by one or more R 8a , or C 3-8 cycloalkyl substituted by one or more R 8b ;
  • Each R 8a is independently deuterium, halogen, C 1-6 alkyl substituted by one or more R 8-a , or C 3-8 cycloalkyl substituted by one or more R 8-b , and each R 8b is independently halogen or C 1-6 alkyl substituted by one or more R 8-a ;
  • Each R 8-a and R 8-b is independently halogen
  • each R 2a is deuterium
  • Ring B is a C 6-10 arylene group
  • R 3 is halogen or C 1-6 alkyl
  • n 0 or 1
  • L is -NHC(O)-
  • R 7a is hydrogen, halogen or C 1-6 alkyl
  • R 7b is hydrogen, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocyclic hydrocarbon substituted by one or more R 7-e ;
  • R 7c is hydrogen, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocyclic hydrocarbon substituted by one or more R 7-e ;
  • R 7-a and R 7-e are independently a C 1-6 alkyl group or a 3-10 membered heterocyclic hydrocarbon group;
  • R4 is C1-6 alkyl
  • R 5 is -C(O)(R 11 ), C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ;
  • Each R 5a is independently hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), C 1-6 alkyl, -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted with one or more R 5-f ;
  • Each R 15 is independently a C 3-8 cycloalkyl, a 3-12 membered heterocycloalkyl, or a 3-12 membered heterocycloalkyl substituted by one or more R 15b ;
  • Each R 15b is independently halogen or C 1-6 alkyl
  • Each R 5-f is independently halogen, hydroxy, -N(R 12 ) 2 or C 1-6 alkyl;
  • Each R 5e is independently halogen or -NR 9 R 10 ;
  • Each R 5f is independently hydroxy or -NR 9 R 10 ;
  • Each of R 9 and R 10 is independently hydrogen, hydroxy, C 1-6 alkyl, 3-12 membered heterocyclic hydrocarbon group, C 1-6 alkyl substituted by one or more R 9a , or 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9c ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9a is independently -N(R 14 ) 2 , 3-12 membered heterocyclic hydrocarbon group, or 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9-c ;
  • Each R 9-c is independently C 1-6 alkyl
  • Each R 9c is independently C 1-6 alkyl
  • Each R 9f is independently halogen, -N(R 14 ) 2 , hydroxy, oxo ( ⁇ O), C 1-6 alkyl, C 1-6 alkyl substituted with one or more R 9 -a , 3-12 membered heterocyclic hydrocarbon group or C 3-8 cyclic hydrocarbon group;
  • Each R 9-a is independently C 1-6 alkyl, hydroxy, halogen, -S(O) 2 (R 17 ) or -N(R 16 ) 2 ;
  • Each R 11 is independently a C 1-6 alkyl group, a 3-10 membered heterocyclic hydrocarbon group, or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 11c ;
  • Each R 11c is independently C 1-6 alkyl
  • Each R 12 is independently hydrogen or C 1-6 alkyl
  • Each R 14 is independently hydrogen or C 1-6 alkyl
  • Each R 16 is independently C 1-6 alkyl
  • Each R 17 is independently C 1-6 alkyl
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2, 3 or 4;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CH
  • R1 is -NH2 ;
  • Ring A is C 6-10 aryl or 5-10 membered heteroaryl
  • each R 2 is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -N(R 8 ) 2 , -S(O) 2 (R 8 ) or -C(O)N(R 8 ) 2 , wherein said C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ;
  • n 2 or 3;
  • Each R 8 is independently hydrogen, C 1-6 alkyl, or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently deuterium, halogen or hydroxy
  • Each R 2a is independently deuterium or halogen
  • Ring B is a C 6-10 arylene group
  • R 3 is halogen or C 1-6 alkyl
  • n 0 or 1
  • L is -NHC(O)-
  • R 7a is hydrogen, halogen or C 1-6 alkyl
  • R 7b is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocyclic hydrocarbon group, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • R 7c is hydrogen, halogen, C 1-6 alkyl, 3-10 membered heterocyclic hydrocarbon group, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 7-e ;
  • R 7-a and R 7-e are independently halogen, hydroxyl or C 1-6 alkyl;
  • R4 is C1-6 alkyl
  • R 5 is -C(O)(R 11 ), -P(O)(R 18 ) 2 , C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl, C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ;
  • each R 5a is independently hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), C 1-6 alkyl, -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl substituted with one or more R 5-b , or 3-12 membered heterocycloalkyl substituted with one or more R 5-f ;
  • Each R 5-b is independently halogen, hydroxy, -OC 1-6 alkyl or 3-12 membered heterocyclic hydrocarbon group;
  • Each R 15 is independently a C 3-8 cycloalkyl, a 3-12 membered heterocycloalkyl, or a 3-12 membered heterocycloalkyl substituted by one or more R 15b ;
  • Each R 15b is independently halogen or C 1-6 alkyl
  • Each R 5-f is independently halogen, hydroxy, oxo, -N(R 12 ) 2 , C 1-6 alkyl, -OC 1-6 alkyl, C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, or C 1-6 alkyl substituted by one or more R 5-a-1 ;
  • Each R 5-a-1 is halogen or hydroxy
  • Each R 5e is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 ;
  • Each R 5f is independently halogen, hydroxy, cyano, C 1-6 alkyl, -OC 1-6 alkyl or -NR 9 R 10 ;
  • each R 9 and R 10 is independently hydrogen, hydroxy, C 1-6 alkyl, -C(O)N(R 13 ) 2 , C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl, C 1-6 alkyl substituted by one or more R 9a , C 3-8 cycloalkyl substituted by one or more R 9b , or 3-12 membered heterocycloalkyl substituted by one or more R 9c ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9a is independently halogen, hydroxy, -N(R 14 ) 2 , 3-12 membered heterocyclic hydrocarbon group, or 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9-c. Cycloalkyl;
  • Each R 9-c is independently C 1-6 alkyl
  • Each R 9b is independently deuterium, halogen, cyano, -N(R 14 ) 2 , hydroxyl or C 1-6 alkyl;
  • Each R 9c is independently C 1-6 alkyl
  • each R 9f is independently halogen, -N(R 14 ) 2 , hydroxy, oxo ( ⁇ O), C 1-6 alkyl, -S(O) 2 (R 19 ), C 1-6 alkyl substituted with one or more R 9- a , 3-12 membered heterocycloalkyl, -OC 1-6 alkyl or C 3-8 cycloalkyl;
  • Each R 9-a is independently C 1-6 alkyl, hydroxy, halogen, -S(O) 2 (R 17 ), -NH 2 , -NH(R 16 ) or -N(R 16 ) 2 ;
  • Each R 11 is independently a C 1-6 alkyl group, a 3-10 membered heterocyclic hydrocarbon group, or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 11c ;
  • Each R 11c is independently hydroxy or C 1-6 alkyl
  • Each R 12 is independently hydrogen or C 1-6 alkyl
  • Each R 13 is independently hydrogen or C 1-6 alkyl
  • Each R 14 is independently hydrogen or C 1-6 alkyl
  • Each R 16 is independently C 1-6 alkyl
  • Each R 17 is independently C 1-6 alkyl
  • Each R 18 is independently C 1-6 alkyl
  • Each R 19 is independently C 1-6 alkyl
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • X is CH
  • R1 is -NH2 ;
  • Ring A is C 6-10 aryl or 5-10 membered heteroaryl
  • each R 2 is independently halogen, -OC 1-6 alkyl or -C(O)N(R 8 ) 2 , wherein said -OC 1-6 alkyl is each independently unsubstituted or substituted with one or more R 2a ;
  • n 2 or 3;
  • Each R 8 is independently hydrogen or C 1-6 alkyl substituted with one or more R 8a ;
  • Each R 8a is independently deuterium or halogen
  • each R 2a is deuterium
  • Ring B is a C 6-10 arylene group
  • R 3 is halogen or C 1-6 alkyl
  • n 0 or 1
  • L is -NHC(O)-
  • R 7a is hydrogen, halogen or C 1-6 alkyl
  • R 7b is hydrogen, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocyclic hydrocarbon substituted by one or more R 7-e ;
  • R 7c is hydrogen, C 1-6 alkyl substituted by one or more R 7-a , or 3-10 membered heterocyclic hydrocarbon substituted by one or more R 7-e ;
  • R 7-a and R 7-e are independently C 1-6 alkyl
  • R4 is C1-6 alkyl
  • R 5 is -C(O)(R 11 ), C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more R 5e , 3-12 membered heterocycloalkyl, 3-12 membered heterocycloalkyl substituted by one or more R 5f , or -C(O)N(R 9 ) 2 ;
  • Each R 5a is independently hydroxy, -NR 9 R 10 , -S(O) 2 (R 11 ), C 1-6 alkyl, -OC 1-6 alkyl, -OR 15 , 3-12 membered heterocycloalkyl, or 3-12 membered heterocycloalkyl substituted with one or more R 5-f ;
  • Each R 15 is independently a C 3-8 cycloalkyl, a 3-12 membered heterocycloalkyl, or a 3-12 membered heterocycloalkyl substituted by one or more R 15b ;
  • Each R 15b is independently halogen or C 1-6 alkyl
  • Each R 5-f is independently halogen, hydroxy, -N(R 12 ) 2 or C 1-6 alkyl;
  • Each R 5e is independently halogen or -NR 9 R 10 ;
  • Each R 5f is independently hydroxy or -NR 9 R 10 ;
  • Each of R 9 and R 10 is independently hydrogen, hydroxy, C 1-6 alkyl, 3-12 membered heterocyclic hydrocarbon group, C 1-6 alkyl substituted by one or more R 9a , or 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9c ;
  • R 9 and R 10 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • R 9 or two R 9 together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9f ;
  • Each R 9a is independently -N(R 14 ) 2 , 3-12 membered heterocyclic hydrocarbon group, or 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 9-c ;
  • Each R 9-c is independently C 1-6 alkyl
  • Each R 9c is independently C 1-6 alkyl
  • Each R 9f is independently halogen, -N(R 14 ) 2 , hydroxy, oxo ( ⁇ O), C 1-6 alkyl, C 1-6 alkyl substituted with one or more R 9 -a , 3-12 membered heterocyclic hydrocarbon group or C 3-8 cyclic hydrocarbon group;
  • Each R 9-a is independently C 1-6 alkyl, hydroxy, halogen, -S(O) 2 (R 17 ) or -N(R 16 ) 2 ;
  • Each R 11 is independently a C 1-6 alkyl group, a 3-10 membered heterocyclic hydrocarbon group, or a 3-10 membered heterocyclic hydrocarbon group substituted by one or more R 11c ;
  • Each R 11c is independently C 1-6 alkyl
  • Each R 12 is independently hydrogen or C 1-6 alkyl
  • Each R 14 is independently hydrogen or C 1-6 alkyl
  • Each R 16 is independently C 1-6 alkyl
  • Each R 17 is independently C 1-6 alkyl
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3;
  • heteroatom species are independently selected from one, two or more of N, O and S, and the number of heteroatoms is independently 1, 2 or 3.
  • the compound represented by formula (I) is a compound represented by formula (I-1):
  • X, R 1 , R 2 , R 4 , R 5 , R 7a , R 7b , R 7c , m and ring A are as defined in any embodiment of the present invention.
  • the compound represented by formula (I) is a compound represented by formula (I-2):
  • R 2 , R 5 , R 7a , R 7b , R 7c , m and ring A are as defined in any embodiment of the present invention.
  • the compound represented by formula (I) is a compound represented by formula (I-3):
  • n' is 0, 1, 2, 3 or 4;
  • X, R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , n, Ring B and L are as defined in any embodiment of the present invention.
  • the compound represented by formula (I) is a compound represented by formula (I-4):
  • X 1 , X 2 , X 3 and X 4 are each independently N, -CH or -CR 2' ;
  • each R 2' is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -N(R 8 ) 2 or -S(O) 2 (R 8 ), wherein said C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each independently unsubstituted or substituted with one or more R 2a ;
  • X, R 1 , R 2a , R 3 , R 4 , R 5 , R 7 , R 8 , n, Ring B and L are as defined in any embodiment of the present invention.
  • each R 2' is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl or C 2-6 alkynyl, wherein the C 1-6 alkyl , -OC 1-6 alkyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ; preferably, each R 2' is independently -OC 1-6 alkyl.
  • the compound represented by formula (I) is a compound represented by formula (I-5):
  • R 2-1 is halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -N(R 8 ) 2 or -S(O) 2 (R 8 ), wherein the C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ;
  • R 2-2 is hydrogen or halogen
  • X, R 1 , R 2a , R 3 , R 4 , R 5 , R 7 , R 8 , n, Ring B and L are as defined in any embodiment of the present invention.
  • R 2-1 is halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl or C 2-6 alkynyl, wherein the C 1-6 alkyl, -OC 1-6 alkyl and C 2-6 alkynyl are each independently unsubstituted or substituted by one or more R 2a ; preferably, R 2-1 is -OC 1-6 alkyl.
  • the compound represented by formula (I) is a compound represented by formula (I-6):
  • X, R 1 , R 2 , R 3 , R 7 , R 4 , R 9 , L, ring A, ring B, m and n are as defined in any embodiment of the present invention.
  • the compound represented by formula (I) is a compound represented by formula (I-7) or formula (I-8):
  • n' is 0, 1, 2, 3 or 4;
  • X, R 1 , R 2 , R 3 , R 7a , R 7b , R 7c , R 4 , R 9 , L, R 7 , Ring A, Ring B, m and n are as defined in any embodiment of the present invention.
  • the compound represented by formula (I) is a compound represented by formula (I-9), formula (I-10) or formula (I-11):
  • n' is 0, 1, 2, 3 or 4;
  • R 1 , R 2 , R 7a , R 7b , R 7c , R 4 , R 9 , R 18 and R 11 are as defined in any embodiment of the present invention.
  • the compound represented by formula (I) is a compound represented by formula (I-12):
  • X 1 , X 2 , X 3 and X 4 are each independently N, CH or CR 2' ;
  • each R 2' is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -N(R 8 ) 2 or -S(O) 2 (R 8 ), wherein said C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each independently unsubstituted or substituted with one or more R 2a ;
  • X, R 1 , R 2a , R 3 , R 4 , R 5 , R 7 , R 8 and n are as defined in any embodiment of the present invention.
  • each R 2' is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl or C 2-6 alkynyl, wherein said C 1-6 alkyl, -OC 1-6 alkyl and C 2-6 alkynyl are each independently unsubstituted or substituted with one or more R 2a .
  • X1 , X2 and X4 are each independently N or CH, and X3 is CR2' ; or, X1 and X4 are each independently N or CH, and X3 and X2 are CR2 ' ; preferably, X1 , X2 and X4 are each independently N or CH, and X3 is CR2 ' .
  • the compound represented by formula (I) is a compound represented by formula (I-13), formula (I-14), formula (I-15), formula (I-16), formula (I-17) or formula (I-18):
  • X 1 , X 2 , X 3 and X 4 are each independently N, CH or CR 2' ;
  • each R 2' is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, -N(R 8 ) 2 or -S(O) 2 (R 8 ), wherein said C 1-6 alkyl, -OC 1-6 alkyl, C 2-6 alkenyl and C 2-6 alkynyl are each independently unsubstituted or substituted with one or more R 2a ;
  • R 5-1 is C 1-6 alkyl substituted by one or more R 5-1-a ; each R 5-1-a is independently hydroxy, C 1-6 alkyl, -OC 1-6 alkyl, 3-12 membered heterocyclic hydrocarbon group, 3-12 membered heterocyclic hydrocarbon group substituted by one or more R 5-f , NR 9 R 10 or -S(O) 2 (R 11 );
  • R 5-2 is a C 3-8 cycloalkyl group substituted by one or more R 5e , a 3-12 membered heterocycloalkyl group, -P(O)(R 18 ) 2 , or a 3-12 membered heterocycloalkyl group substituted by one or more R 5f ;
  • X, R1 , R2a , R3 , R4 , R5e , R5f , R7a , R7b , R7c , R8, R9 , R10 , R11 , R15 , R18 , R5 -f and n are as defined in any embodiment of the present invention.
  • X1 , X2 and X4 are each independently N or CH, and X3 is CR2' ; or, X1 and X4 are each independently N or CH, and X3 and X2 are CR2 ' ; preferably, X1 , X2 and X4 are each independently N or CH, and X3 is CR2 ' .
  • each R 2' is independently halogen, cyano, C 1-6 alkyl, -OC 1-6 alkyl or C 2-6 alkynyl, wherein said C 1-6 alkyl, -OC 1-6 alkyl and C 2-6 alkynyl are each independently unsubstituted or substituted with one or more R 2a .
  • R 5-1-a is hydroxy, C 1-6 alkyl, -OC 1-6 alkyl or -S(O) 2 (R 11 ).
  • R 5-2 is C 3-8 cycloalkyl, 3-12 membered heterocycloalkyl or 3-12 membered heterocycloalkyl substituted by one or more R 5e .
  • X is CH.
  • R 1 is -NH 2 .
  • R2 is fluoro, -O-methyl or For example -O-methyl or
  • R2 is fluoro, -O-methyl, -O-CD 3 , -O-CHF 2 , -O-CF 2 Cl, cyano, -O-ethyl, chloro, -CF 3 , -CHF 2 , -O-CF 3 , methyl or For example, fluorine, chlorine, -O-methyl or For example -O-methyl or
  • R2 is fluoro, -O-methyl, -O-CD 3 , -O-CHF 2 , -O-CF 2 Cl, cyano, -O-ethyl, chloro, -CF 3 , -CHF 2 , -O-CF 3 , methyl,
  • Ring A is phenyl
  • ring A is phenyl or pyridyl, preferably For example
  • ring B is phenylene, for example
  • L is -N(H)C(O)-.
  • R3 is fluoro, chloro or methyl.
  • the end marked with * is connected to L.
  • R7 is Best For example
  • R7 is Best For example
  • R7 is Best More preferred
  • R4 is methyl
  • R 5 is For example
  • R 5 is For example
  • R 5 is For example
  • R 5 is For example
  • the compound represented by formula (I) is any of the following compounds:
  • the pharmaceutically acceptable salt of the compound represented by formula (I) is any of the following compounds:
  • the present invention also provides a pharmaceutical composition, comprising (a therapeutically effective amount of) substance A and a pharmaceutically acceptable excipient, wherein the substance A is a compound as shown in formula (I) as described in any scheme of the present invention, a stereoisomer thereof or a pharmaceutically acceptable salt thereof.
  • the present invention also provides a use of a compound as shown in formula (I) according to any embodiment of the present invention, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, or the above-mentioned pharmaceutical composition in the preparation of a FGFR2 inhibitor.
  • the FGFR2 inhibitor can be used in mammalian organisms; it can also be used in vitro, mainly for experimental purposes, for example: as a standard sample or a control sample for comparison, or prepared into a kit according to conventional methods in the art to provide rapid detection of the inhibitory effect of FGFR2.
  • the present invention also provides a compound as shown in formula (I) according to any embodiment of the present invention, its stereoisomer or pharmaceutically acceptable salt or the above-mentioned pharmaceutical composition for use in the preparation of a drug for treating and/or preventing a disease associated with FGFR2; preferably, the compound as shown in formula (I), its stereoisomer or pharmaceutically acceptable salt or the above-mentioned pharmaceutical composition is a therapeutically effective amount, and/or, the disease associated with FGFR2 is a disease associated with abnormal activation of FGFR2.
  • the disease may be cancer, and the cancer is preferably bile duct cancer, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, bladder cancer, ovarian cancer, colorectal cancer, endometrial cancer or urothelial cancer, and the cancer is more preferably bile duct cancer, gastric cancer or endometrial cancer, such as gastric cancer, and the lung cancer is more preferably small cell lung cancer.
  • the cancer is preferably bile duct cancer, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, bladder cancer, ovarian cancer, colorectal cancer, endometrial cancer or urothelial cancer
  • the cancer is more preferably bile duct cancer, gastric cancer or endometrial cancer, such as gastric cancer
  • the lung cancer is more preferably small cell lung cancer.
  • the present invention also provides a use of a compound as shown in formula (I) according to any embodiment of the present invention, a stereoisomer thereof or a pharmaceutically acceptable salt thereof or the above-mentioned pharmaceutical composition in the preparation of a drug for treating and/or preventing cancer; preferably, the compound as shown in formula (I), its stereoisomer or a pharmaceutically acceptable salt thereof or the above-mentioned pharmaceutical composition is a therapeutically effective amount, and/or the cancer is preferably bile duct cancer, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, bladder cancer, ovarian cancer, colorectal cancer, uterine cancer
  • the cancer is more preferably bile duct cancer, gastric cancer or endometrial cancer, such as gastric cancer, and the lung cancer is more preferably small cell lung cancer.
  • the present invention provides a method for inhibiting FGFR2, comprising administering to a patient a compound as shown in formula (I) according to any embodiment of the present invention, a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or the above-mentioned pharmaceutical composition; preferably, the compound as shown in formula (I), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, or the above-mentioned pharmaceutical composition is in a therapeutically effective amount.
  • the present invention provides a method for treating and/or preventing a disease associated with FGFR2, the method comprising administering to a patient a compound as shown in formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or the above-mentioned pharmaceutical composition as described in any scheme of the present invention; preferably, the compound as shown in formula (I), a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, or the above-mentioned pharmaceutical composition is in a therapeutically effective amount, and/or, the disease associated with FGFR2 is a disease associated with abnormal activation of FGFR2.
  • the disease may be cancer, and the cancer is preferably bile duct cancer, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, bladder cancer, ovarian cancer, colorectal cancer, endometrial cancer, or urothelial cancer, and the cancer is more preferably bile duct cancer, gastric cancer, or endometrial cancer, such as gastric cancer, and the lung cancer is more preferably small cell lung cancer.
  • the cancer is preferably bile duct cancer, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, bladder cancer, ovarian cancer, colorectal cancer, endometrial cancer, or urothelial cancer
  • the cancer is more preferably bile duct cancer, gastric cancer, or endometrial cancer, such as gastric cancer
  • the lung cancer is more preferably small cell lung cancer.
  • the present invention provides a method for treating and/or preventing cancer, the method comprising administering to a patient a compound as shown in formula (I) according to any embodiment of the present invention, a stereoisomer thereof or a pharmaceutically acceptable salt thereof, or the above-mentioned pharmaceutical composition; preferably, the compound as shown in formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, or the above-mentioned pharmaceutical composition is in a therapeutically effective amount, and/or, the cancer is preferably bile duct cancer, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric cancer, bladder cancer, ovarian cancer, colorectal cancer, endometrial cancer or urothelial cancer, the cancer is more preferably bile duct cancer, gastric cancer or endometrial cancer, such as gastric cancer, and the lung cancer is more preferably small cell lung cancer.
  • the cancer is preferably bile duct cancer, liver cancer, breast cancer, prostate cancer, lung cancer, thyroid cancer, gastric
  • the present invention also provides a method for preparing the compound represented by formula (I), its stereoisomers or pharmaceutically acceptable salts thereof, which is any one of the following methods:
  • Method 1 It comprises the following steps: in a solvent, a compound represented by formula (Ia) and a compound represented by formula (Ib) are subjected to Sonogashira reaction to obtain a compound represented by formula (I);
  • X 1 is a halogen
  • X, R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , m, n, ring A, ring B and L are as defined in any embodiment of the present invention.
  • the Sonogashira reaction operation and conditions are conventional reaction operations and conditions for such reactions in the art, and the following conditions are particularly preferred in the present invention:
  • the X 1 is Br
  • the solvent is a nitrogen-containing compound solvent, such as N,N-dimethylformamide and/or triethylamine, and N,N-dimethylformamide A mixed solvent of formamide and triethylamine;
  • the Sonogashira reaction is carried out under the action of a palladium catalyst;
  • the palladium catalyst is preferably a divalent palladium catalyst and/or a zero-valent palladium catalyst, more preferably dichloro[bis(diphenylphosphinophenyl)ether]palladium and/or tetrakis(triphenylphosphine)palladium, for example, a mixture of dichloro[bis(diphenylphosphinophenyl)ether]palladium and tetrakis(triphenylphosphine)palladium;
  • the Sonogashira reaction is carried out under the action of a base;
  • the base is preferably an organic amine, such as triethylamine;
  • Method 2 It comprises the following steps: in a solvent, a compound as represented by formula (Ic) is subjected to a deprotection reaction to prepare a compound as represented by formula (I);
  • R 5' is -C(O)-R 11' , C 1-6 alkyl substituted by one or more R 5a' , C 3-8 cycloalkyl substituted by one or more -NYR 9 , or 3-12 membered heterocycloalkyl substituted by one or more -NYR 9 , each R 5a' is independently -NYR 9 or 3-12 membered heterocycloalkyl substituted by one or more Y, each Y is independently an amino protecting group;
  • R 9' is a 3-12 membered heterocyclic hydrocarbon group substituted by one or more Ys;
  • R 9 and R 9' together with the nitrogen atom to which they are commonly attached form a 3-12 membered heterocyclic hydrocarbon group substituted by one or more -NYR 14 or a 3-12 membered heterocyclic hydrocarbon group substituted by one or more Y;
  • R 11' is a 3-12 membered heterocyclic hydrocarbon group substituted by one or more Ys;
  • R 5 is -C(O)R 11 , -C(O)N(R 9 ) 2 , C 1-6 alkyl substituted by one or more R 5a , C 3- 8 cycloalkyl substituted by one or more -NHR 9 , or 3-12 membered heterocycloalkyl substituted by one or more -NHR 9 ; each R 5a is independently -NHR 9 or 3-12 membered heterocycloalkyl;
  • X, R 1 , R 2 , R 3 , R 4 , R 7 , R 9 , R 14 , m, n, ring A, ring B and L are as defined in any embodiment of the present invention.
  • R 5' is a C 1-6 alkyl substituted by one or more R 5a' , a C 3-8 cycloalkyl substituted by one or more -NYR 9 , or a 3-12 membered heterocycloalkyl substituted by one or more -NYR 9 , each R 5a' is independently -NYR 9 or a 3-12 membered heterocycloalkyl substituted by one or more Y, and each Y is independently an amino protecting group;
  • R 5 is C 1-6 alkyl substituted by one or more R 5a , C 3-8 cycloalkyl substituted by one or more -NHR 9 , or 3-12 membered heterocycloalkyl substituted by one or more -NHR 9 ; each R 5a is independently -NHR 9 or 3-12 membered heterocycloalkyl;
  • X, R 1 , R 2 , R 3 , R 4 , R 7 , R 9 , m, n, ring A, ring B and L are as defined in any embodiment of the present invention.
  • the solvent is a halogenated hydrocarbon solvent, such as dichloromethane;
  • said Y is tert-butyloxycarbonyl
  • the deprotection reaction is carried out under the action of an acid, and the acid is preferably an organic acid, such as trifluoroacetic acid.
  • the present invention also provides a method for preparing a compound as shown in formula (I), a stereoisomer thereof or a pharmaceutically acceptable salt thereof, comprising the following steps: in a solvent, a compound as shown in formula (Id) is subjected to a condensation reaction with ammonia or an ammonia salt to prepare a compound as shown in formula (I);
  • R 5′′ is hydroxyl or halogen
  • X, R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 9 , m, n, ring A, ring B and L are as defined in any embodiment of the present invention.
  • the solvent is a nitrogen-containing compound solvent or a halogenated hydrocarbon solvent, such as N,N-diisopropylethylamine or dichloromethane;
  • R 5" is hydroxyl
  • the condensation reaction is carried out under the action of a condensation reagent, and the condensation reagent is preferably 2-(7-azabenzotriazole)-N,N,N',N'-tetramethyluronium hexafluorophosphate; further preferably, the condensation reaction is carried out under the action of a condensation reagent and a base, and the base is preferably N,N-diisopropylethylamine;
  • ammonium salt is ammonium hydrochloride.
  • the present invention also provides a compound of formula (Ia) or formula (Ic) as shown below:
  • X 1 , X, R 1 , R 2 , R 3 , R 4 , R 5' , R 7 , m, n, ring A, ring B and L are as defined in any embodiment of the present invention
  • the compound of formula (Ia) or formula (Ic) is any of the following compounds,
  • the present invention also provides a compound of formula (Id) as shown below:
  • X, R 1 , R 2 , R 3 , R 4 , R 5′′ , R 7 , m, n, ring A, ring B and L are as defined in any embodiment of the present invention
  • the compound of formula (Id) is any of the following compounds:
  • pharmaceutically acceptable salt refers to a salt prepared from a compound of the present invention and a relatively nontoxic, pharmaceutically acceptable acid or base.
  • a base addition salt can be obtained by contacting a neutral form of such compound with a sufficient amount of a pharmaceutically acceptable base in a pure solution or a suitable inert solvent.
  • an acid addition salt such as a mesylate, can be obtained by contacting a neutral form of such compound with a sufficient amount of a pharmaceutically acceptable acid in a pure solution or a suitable inert solvent.
  • halogen refers to fluorine, chlorine, bromine, iodine.
  • alkyl refers to a straight or branched, saturated, or alkyl radical having a specified number of carbon atoms (e.g., C 1-6 or C 1 -C 6 , C 1-4 or C 1 -C 4 ).
  • the alkyl group includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and the like.
  • alkylene refers to a divalent alkyl group, ie, one hydrogen atom in an alkyl group is replaced, wherein the alkyl group is as defined above, for example, C 1-6 alkylene.
  • alkenyl refers to a linear or branched, unsaturated, monovalent hydrocarbon group having a specified number of carbon atoms (eg, C2-6 or C2 - C6 ) and having a carbon-carbon sp2 double bond.
  • alkynyl refers to a linear or branched, unsaturated, monovalent hydrocarbon group having a specified number of carbon atoms (e.g., C 2-6 or C 2 -C 6 ) and having a carbon-carbon sp 3 triple bond. Alkynyl groups include, but are not limited to: wait.
  • alkyl group is as defined above.
  • alkyl group is as defined above.
  • cycloalkyl refers to a non-aromatic saturated or partially unsaturated cycloalkyl having a specified number of ring carbon atoms (e.g., C 3-8 or C 3 -C 8 ), including cycloalkyl and cycloalkenyl.
  • the cycloalkyl may be monocyclic or polycyclic, and may be a cyclic, spirocyclic or bridged ring structure.
  • the cycloalkyl includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
  • cycloalkyl refers to a saturated monocyclic, spirocyclic, bridged or paracyclic cyclic group having a specified number of ring carbon atoms (e.g., C 3-8 or C 3 -C 8 , C 6-8 or C 6 -C 8 ) and the ring atoms consisting only of carbon atoms.
  • Cycloalkyl includes, but is not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.
  • cycloalkenyl refers to an unsaturated monocyclic, spirocyclic, bridged or paracyclic cyclic group having a specified number of carbon atoms (eg, C3-8 or C3 - C8 , C6-8 or C6 - C8 ), the ring atoms of which consist only of carbon atoms, and which has no aromaticity.
  • cycloalkylene refers to a divalent cycloalkyl radical, wherein cycloalkyl is as defined above.
  • heterocyclic hydrocarbon group refers to a non-aromatic saturated or partially unsaturated cyclic group having a specified number of ring atoms (e.g., 3-10 members, 3-12 members), a specified number of heteroatoms (e.g., 1, 2, 3 or 4), and a specified type of heteroatoms (1, 2 or 3 of N, O and S), including heterocyclic alkyl or heterocyclic alkenyl.
  • the heterocyclic hydrocarbon group may be monocyclic or polycyclic, and may be a paracyclic, spirocyclic or bridged ring structure.
  • Heterocyclic hydrocarbon groups include, but are not limited to, oxetanyl (e.g., ), azetidinyl (e.g., ), tetrahydropyrrolyl, piperazinyl, piperidinyl, morpholinyl, etc., for example Another example
  • heterocycloalkyl refers to a saturated monocyclic, spirocyclic, bridged or paracyclic cyclic group with a specified number of ring atoms (e.g., 3-6, 3-10, 3-12, 6-10, 6-12), a specified number of heteroatoms (e.g., 1, 2 or 3), and a specified type of heteroatoms (1, 2 or 3 of N, O and S).
  • ring atoms e.g., 3-6, 3-10, 3-12, 6-10, 6-12
  • heteroatoms e.g., 1, 2 or 3
  • a specified type of heteroatoms 1, 2 or 3 of N, O and S
  • Heterocycloalkyl includes, but is not limited to, oxetane (e.g., ), azetidinyl (e.g., ), tetrahydropyrrolyl, piperazinyl, piperidinyl, morpholinyl, etc., for example Another example
  • heterocycloalkenyl refers to an unsaturated monocyclic, spirocyclic, bridged or paracyclic cyclic group having a specified number of ring atoms (e.g., 3-6 members, 3-10 members, 3-12 members, 6-10 members, 6-12 members), a specified number of heteroatoms (e.g., 1, 2, 3 or 4), a specified type of heteroatoms (one or more of N, O and S), which is not aromatic.
  • ring atoms e.g., 3-6 members, 3-10 members, 3-12 members, 6-10 members, 6-12 members
  • heteroatoms e.g., 1, 2, 3 or 4
  • a specified type of heteroatoms one or more of N, O and S
  • heterocycloalkylene refers to a divalent heterocycloalkyl group, wherein heterocycloalkyl is as defined above.
  • aryl refers to an aromatic group having a specified number of ring carbon atoms (eg, C6-10 or C6 - C10 ). Examples of aryl groups include, without limitation, phenyl or naphthyl.
  • arylene refers to a divalent aromatic group, wherein aryl is as defined above.
  • heteroaryl refers to a cyclic group having a specified number of ring atoms (e.g., 5-10 members, 5-6 members, 8-10 members), a specified number of heteroatoms (e.g., 1, 2 or 3), and a specified type of heteroatoms (e.g., one, two or more of N, O and S), which can be monocyclic or polycyclic (e.g., cyclic, spirocyclic and bridged), and at least one ring is aromatic (in accordance with Huckel's rule).
  • the heteroaryl group is connected to other fragments in the molecule through an aromatic ring or a non-aromatic ring.
  • Heteroaryl includes, but is not limited to, furanyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, pyridyl, pyrimidinyl, indolyl or 1,2,3,4-tetrahydroisoquinolyl, etc., for example
  • heteroarylene refers to a divalent heteroaryl group, wherein heteroaryl is as defined above.
  • one or more means 1, 2, 3, 4, 5, 6, 7, 8, 9 or more.
  • the group when its connection site is not specified, can be connected to other parts of the molecule through any permissible connection site; for example It means that it can be connected to other parts of the molecule through any permissible ring atom on any ring.
  • the attachment site can be on a four-membered heterocyclic ring (e.g. ), or on a six-membered heterocyclic ring (e.g. ).
  • connection direction of the linking groups listed in the present invention is connected in the same direction as the reading order from left to right, as shown below:
  • the connecting group L1 is -CD-, in which case -CD- connects ring A and ring B in the same direction as the reading order from left to right to form Rather than constitute Specifically in the present invention, L is -N(H)C(O)-, which means that N is connected to ring B via a single bond, rather than C being connected to ring B.
  • the compound shown in formula (I) of the present invention may contain one or more chiral centers and exist in different optically active forms.
  • the compound contains one chiral center, the compound contains enantiomers.
  • the present invention includes these two isomers and mixtures of isomers, such as racemic mixtures. Enantiomers can be resolved by methods known in the art, such as crystallization and chiral chromatography. When the compound shown in formula (I) contains more than one chiral center, diastereomers may exist.
  • the present invention includes resolved optically pure specific isomers and mixtures of diastereomers. Diastereomers can be resolved by methods known in the art, such as crystallization and preparative chromatography.
  • stereoisomer includes conformational isomers and configurational isomers, wherein configurational isomers mainly include cis-trans isomers and optical isomers.
  • the compounds of the present invention may exist in the form of stereoisomers, and therefore encompass all possible stereoisomer forms, including but not limited to cis-trans isomers, enantiomers, diastereomers, atropisomers, etc.
  • the compounds of the present invention may also exist in the form of any combination or any mixture of the aforementioned stereoisomers, such as mesomorphs, racemates, equal mixtures of atropisomers, etc.
  • a single enantiomer, a single diastereomer or a mixture thereof, or a single atropisomer or a mixture thereof When the compounds of the present invention contain olefin double bonds, unless otherwise specified, they include cis-isomers and trans-isomers, and any combination thereof.
  • the atropisomers of the present invention are stereoisomers of axial or planar chirality generated based on restricted intramolecular rotation.
  • the present invention provides compounds represented by the above-mentioned structures, or their cis-trans isomers, meso-isomers, racemates, enantiomers, diastereomers, atropisomers, tautomers or mixtures thereof, wherein “mixtures thereof” include any stereoisomer (e.g., cis-trans isomers, enantiomers, diastereomers, atropisomers), tautomers and/or mixtures thereof.
  • mixture refers to any form of mixture between compounds (mesomers, racemates), such as a mixture of cis-trans isomers, a mixture of enantiomers and diastereomers, a mixture of diastereomers, a mixture of atropisomers, or a mixture of cis-trans isomers and racemates, a mixture of enantiomers and diastereomers, a mixture of cis-trans isomers and tautomers, a mixture of atropisomers and a mixture of diastereomers, etc.
  • pharmaceutically acceptable excipients refers to excipients and additives used in the production of drugs and the preparation of prescriptions. It is all substances contained in drug preparations except active ingredients. Please refer to Part IV of the Pharmacopoeia of the People's Republic of China (2020 Edition), or Handbook of Pharmaceutical Excipients (Raymond C Rowe, 2009 Sixth Edition).
  • treatment refers to therapeutic treatment.
  • treatment means: (1) ameliorating the disease or one or more biological manifestations of the condition, (2) interfering with (a) one or more points in the biological cascade leading to or causing the condition or (b) one or more biological manifestations of the condition, (3) ameliorating one or more symptoms, effects, or side effects associated with the condition or one or more symptoms, effects, or side effects associated with the condition or its treatment, or (4) slowing the progression of the condition or one or more biological manifestations of the condition.
  • FGFR2 abnormality refers to "abnormal activation of FGFR2", and its molecular mechanisms mainly include (1) gene amplification; (2) gene mutation; (3) gene fusion caused by gene translocation, etc.
  • therapeutically effective amount refers to an amount administered to a patient that is sufficient to effectively treat a disease.
  • the therapeutically effective amount will vary depending on the type of compound, the type of disease, the severity of the disease, the age of the patient, etc., but can be adjusted by those skilled in the art as appropriate.
  • the reagents and raw materials used in the present invention are commercially available.
  • the positive and progressive effects of the present invention are that the compounds of the present invention have good inhibitory activity and selectivity against FGFR2 abnormalities, and show good proliferation inhibitory activity against human gastric cancer cells SNU-16 compared to human small cell lung cancer cells DMS114 and human bladder cancer cells RT112/84.
  • the compounds of the present invention can be well absorbed after oral administration and have good drug exposure in rats.
  • N-iodosuccinimide N-iodosuccinimide

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

L'invention concerne un composé cyclique hétéroaromatique tel que représenté par la formule (I), un stéréoisomère de celui-ci ou un sel pharmaceutiquement acceptable de celui-ci. Le composé cyclique hétéroaromatique a une bonne activité inhibitrice et une bonne sélectivité sur une anomalie dans FGFR2, et a une bonne activité inhibitrice de prolifération sur les cellules cancéreuses gastriques humaines SNU-16 par rapport aux cellules cancéreuses du poumon à petites cellules humaines DMS114 et aux cellules cancéreuses de la vessie humaine RT112/84. Le composé cyclique hétéroaromatique peut être bien absorbé après administration orale, et présente une bonne exposition aux médicaments chez le rat.
PCT/CN2024/095527 2023-05-26 2024-05-27 Composé cyclique hétéroaromatique, composition pharmaceutique de celui-ci et utilisation associée Pending WO2024245193A1 (fr)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
CN202310612074 2023-05-26
CN202310612074.X 2023-05-26
CN202310725862.X 2023-06-16
CN202310725862 2023-06-16
CN202310791840 2023-06-29
CN202310791840.3 2023-06-29
CN202311520662 2023-11-14
CN202311520662.7 2023-11-14

Publications (1)

Publication Number Publication Date
WO2024245193A1 true WO2024245193A1 (fr) 2024-12-05

Family

ID=93656711

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2024/095527 Pending WO2024245193A1 (fr) 2023-05-26 2024-05-27 Composé cyclique hétéroaromatique, composition pharmaceutique de celui-ci et utilisation associée

Country Status (1)

Country Link
WO (1) WO2024245193A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006004703A2 (fr) * 2004-06-29 2006-01-12 Amgen Inc. Pyrrolo [2, 3-d] pyrimidines qui modulent l'activite ack1 et lck
WO2010046013A1 (fr) * 2008-10-23 2010-04-29 Merck Patent Gmbh Dérivé d'azaindole
CN114126620A (zh) * 2019-05-13 2022-03-01 传达治疗有限公司 Fgfr抑制剂和其使用方法
WO2022109577A1 (fr) * 2020-11-18 2022-05-27 Relay Therapeutics, Inc. Inhibiteurs de fgfr et leurs procédés de préparation et leurs méthodes d'utilisation
WO2023046117A1 (fr) * 2021-09-23 2023-03-30 3H Pharmaceuticals Co., Ltd. Inhibiteurs de fgfr et leurs procédés d'utilisation

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006004703A2 (fr) * 2004-06-29 2006-01-12 Amgen Inc. Pyrrolo [2, 3-d] pyrimidines qui modulent l'activite ack1 et lck
WO2010046013A1 (fr) * 2008-10-23 2010-04-29 Merck Patent Gmbh Dérivé d'azaindole
CN114126620A (zh) * 2019-05-13 2022-03-01 传达治疗有限公司 Fgfr抑制剂和其使用方法
WO2022109577A1 (fr) * 2020-11-18 2022-05-27 Relay Therapeutics, Inc. Inhibiteurs de fgfr et leurs procédés de préparation et leurs méthodes d'utilisation
WO2023046117A1 (fr) * 2021-09-23 2023-03-30 3H Pharmaceuticals Co., Ltd. Inhibiteurs de fgfr et leurs procédés d'utilisation

Similar Documents

Publication Publication Date Title
CN113166103B (zh) Egfr抑制剂及其应用
WO2021031952A1 (fr) Composé de pyrimidine cyclique à six chaînons substitué par oxygène, son procédé de préparation et son utilisation médicale
WO2021218110A1 (fr) Composé de benzothiazolyle biaryle, son procédé de préparation et son utilisation
CN117083279A (zh) 氧氮杂䓬化合物及其在癌症治疗中的用途
CN102548557B (zh) 用于降低β-淀粉状蛋白生成的化合物
CN104781255B (zh) 作为trka激酶抑制剂的n‑吡咯烷基、n’‑吡唑基‑脲、硫脲、胍和氰基胍化合物
CN118084866A (zh) 稠环化合物
WO2021143701A1 (fr) Composé hétérocyclique de pyrimidine-4(3h)-cétone, son procédé de préparation et son utilisation en médecine et en pharmacologie
CN115835908A (zh) 作为fgfr抑制剂的双环杂环
TW201722933A (zh) 苯內醯胺化合物
WO2015165279A1 (fr) Composés polyfluorés agissant en tant qu'inhibiteurs de la tyrosine kinase de bruton
WO2021190417A1 (fr) Nouvel inhibiteur aminopyrimidine d'egfr
CN113135896A (zh) 作为ret抑制剂的甲基吡唑类衍生物
CN105452257A (zh) 新型稠合嘧啶化合物或其盐
WO2024125642A1 (fr) Inhibiteur de dérivé polycyclique contenant de la pyrimidine, son procédé de préparation et son utilisation
CN108349946B (zh) 作为PI3Kβ抑制剂的喹喔啉和吡啶并吡嗪衍生物
WO2022194269A1 (fr) Nouvel agent de dégradation de l'egfr
CN116768861A (zh) Sos1蛋白降解靶向嵌合体及其组合物、制剂和用途
CN115427035A (zh) Enl/af9 yeats抑制剂
WO2021164746A1 (fr) Composé aryle substitué
JP2022543713A (ja) 窒素含有多環式縮合環系化合物、その薬学的組成物、製造方法及び用途
TW201927787A (zh) 吡咯並三嗪化合物及抑制ｔａｍ激酶之方法
CN105541693B (zh) 芳杂环类衍生物及其在药物上的应用
WO2024094171A1 (fr) Composé aminopyrimidine substitué, son procédé de préparation et son utilisation médicale
CN112513041B (zh) 三环化合物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24814390

Country of ref document: EP

Kind code of ref document: A1