Dihydronaphthyridinone compound, and preparation method therefor and medical use thereof

Abstract

Provided are a dihydronaphthyridinone compound as shown in formula (I), which compound has a selective inhibitory effect on RIPK1, and a pharmaceutically acceptable salt, a stereoisomer, a solvate or a prodrug thereof. In addition, provided are a pharmaceutical composition containing the compound, and the use thereof in the preparation of a drug for treating RIPK1-related diseases or conditions. [Image disponible dans le document PDF, Image available in the PDF document]

Description

DIHYDRONAPHTHYRIDINONE COMPOUND, AND PREPARATION METHOD THEREFOR AND MEDICAL USE THEREOF Technical Field 1 The present disclosure relates to the technical field of medicament, and in particular relates to a dihydronaphthyridinone compound, use thereof as a RIPK1 inhibitor and a pharmaceutical composition prepared thereby. Backgroud [2] Receptor-interacting protein 1 (RIP1) kinase is a Tyrosine Kinase-Like (TKL) family serine / threonine protein kinase involved in innate immune signaling. RIP1 kinase is a protein- containing RHIM domain, with an N-terminal kinase domain and a C-terminal death domain ((2005) Trends Biochem. Sci. 30,151-159). The death domain of RIP1 mediates an interaction with other proteins containing a death domain, and the proteins include Fas and TNFR-1 ((1995) Cell 81 513- 523), TRAIL-R1 and TRAIL-R2 ((1997) Immunity 7,821-830) and TRADD ((1996) Immunity 4,387-396), while RHIM domain is critical for binding other proteins containing a RHIM domain, such as TRIF ((2004) Nat Immunol. 5,503-507), DAI ((2009) EMBO Rep. 10,916-922) and RIP3 ((1999) J. Biol. Chem. 274,16871-16875), (1999) Curr. Biol. 9,539-542), and exerts many of its effects through these interactions. [3] The role for RIP1 in cell signaling has been assessed under various conditions (including TLR3) ((2004) Nat Immunol.5,503-507), TLR4 ((2005) J. Biol. Chem. 280,36560-36566), TRAIL (CellSignal. 2015 Feb; 27(2):306-14) and FAS ((2004) J. Biol. Chem. 279,7925-7933)), but is best understood in the context of mediating signals downstream of the death receptor TNFR1 ((2003) Cell 114,181-190). Engagement of the TNFR by TNF leads to an oligomerization, and a recruitment of multiple proteins, including linear K63-linked polyubiquitinated RIP1 ((2006) Mol. Cell 22,245- 257), TRAF2 / 5 ((2010) J. Mol. Biol. 396,528-539), TRADD ((2008) Nat. Immunol. 9, 1037-1046) and cIAPs ((2008) Proc. Natl. Acad. Sci. USA. 105, 11778-11783), to the cytoplasmic tail of the receptor. The complex that is dependent on RIP1 as a scaffolding protein (i.e. kinase independent), termed complex I, provides a platform for pro-survival signaling through an activation of NFkB and MAP kinases pathways ((2010) Sci. Signal. 115, re4). In addition, binding of TNF to its receptor (by e.g. A20 and CYLD proteins or inhibition of cIAP inhibition) under conditions promoting a deubiquitination of RIP1 results in a receptor internalization and a formation of complex II or DISC (a death-inducing signaling complex) ((2011) Cell Death Dis. 2,e230). Formation of the DISC(contains RIP1, TRADD, FADD and caspase 8) results in an activation of caspase 8 and also an onset of programmed apoptotic cell death in a RIP1 kinase independent manner ((2012) FEBS J 278,877-887). Apoptosis is largely a quiescent form of cell death, and is involved in routine processes such as development and cellular homeostasis. [4] Under conditions where DISC is formed and RIP3 is expressed, but apoptosis is inhibited (such as FADD / caspase 8 deletion, caspase inhibition or viral infection), a third RIP1 kinase-dependent may exist. RIP3 can now enter this complex, become phosphorylated by RIP1 and initiate a caspase- independent programmed necrotic cell apoptosis through an activation of MLKL and PGAM5 ((2012) Cell 148,213-227); ((2012) Cell 148,228-243); ((2012) Proc. Natl. Acad. Sci. USA. 109,5322-5327). As opposed to apoptosis, programmed necrosis (not to be confused with passive necrosis which is not programmed) results in a release of danger -associated molecular patterns (DAMP) from cells. These DAMP are capable of providing a "danger signal" to surrounding cells and tissues, eliciting proinflammatory responses including an inflammasome activation, a cytokine production and a cellular recruiting response (2008 Nat. Rev. Immunol 8,279-289). [5] Dysregulation of RIP1 kinase-mediated programmed cell death has been linked to various inflammations, as demonstrated by use of RIP3 knockout mice (where RIP1-mediated programmed necrosis is completely blocked) and by Necrostatin-1 (a tool inhibitor of RIP1 kinase activity with a poor oral bioavailability). RIP3 knockout mice have been shown to be protective in inflammatory bowel disease (including ulcerative colitis and Crohn's disease) ((2011) Nature 477,330-334), psoriasis ((2011) Immunity 35,572-582), retinal-detachment-induced photoreceptor necrosis ((2010) PNAS 107,21695-21700), retinitis pigmentosa ((2012) Proc. Natl. Acad. Sci., 109:36,14598-14603), cerulein-induced acute pancreatitis ((2009) Cell 137,1100-1111) and sepsis / systemic inflammatory response syndrome (SIRS) ((2011) Immunity 35,908-918). Necrostatin-1 has been shown to be effective in alleviating ischemic brain injury ((2005) Nat. Chem. Biol. 1,112-119), retinal ischemia / reperfusion injury ((2010) J. Neurosci. Res. 88,1569-1576), Huntington's disease ((2011) Cell Death Dis. 2e115), renal ischemia-reperfusion injury ((2012) Kidney Int. 81,751-761), Cisplatin induced kidney injury ((2012) Ren. Fail. 34,373-377) and traumatic brain injury ((2012) Neurochem. Res. 37,1849-1858). Other diseases or conditions regulated at least in part by RIP1- dependent apoptosis, necrosis or cytokine production include hematological and solid organ malignancies ((2013) Genes Dev. 27:1640-1649), bacterial infections and viral infections ((2014) Cell Host&Microbe 15,23-35) (including, but not limited to, tuberculosis and influenza ((2013) Cell 153,1-14)) and lysosomal storage disease (particularly, Gaucher disease, Nature Medicine Advance Online Publication, 19 Jan. 2014, doi: 10.1038 / nm. 3449). [6] A potent and selective small molecule inhibitor of RIP1 kinase activity is capable of blocking RIP1-dependent necrosis, thereby providing a therapeutic effect in diseases or events associated with DAMP, cell death, and / or inflammation. Summary [7] The present disclosure provides a dihydronaphthyridinone compound, which, as a RIPK1 inhibitor, has the advantages of high activity, good selectivity, and low toxicity and side effects. [8] In a first aspect, the present disclosure provides a dihydronaphthyridinone compound, or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, wherein the compound has a structure represented by formula (I): [Image disponible dans le document PDF, Image available in the PDF document] 9 wherein, <com:Math><semantics>10R1<annotation encoding="application / x-tex">10R_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> are each independently hydrogen, halogen, substituted or unsubstituted <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, substituted or unsubstituted C<com:Sub>1-6< / com:Sub> alkoxy or substituted or unsubstituted NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, wherein R<com:Sub>a0< / com:Sub> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> are each independently hydrogen or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; or <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> form together with the nitrogen atom adjacent theretoa 3- to 8-membered nitrogen-containing heterocycloalkyl; the "substituted" in <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math> means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; 11 the definition for <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> are selected from one of the following groups:

[12] (i) R<com:Sub>3< / com:Sub>, R<com:Sub>4< / com:Sub>, R<com:Sub>5< / com:Sub> and R<com:Sub>6< / com:Sub> are each independently hydrogen, halogen, substituted or unsubstituted <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl, or substituted or unsubstituted <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; <com:Math><semantics>13(ii)<annotation encoding="application / x-tex">13(ii)< / annotation>< / semantics>< / com:Math> R<com:Sub>3< / com:Sub> and R<com:Sub>4< / com:Sub> form together with the carbon atom adjacent thereto a substituted or unsubstituted C<com:Sub>3-8< / com:Sub> cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; R<com:Sub>5< / com:Sub> and R<com:Sub>6< / com:Sub> are each independently hydrogen, halogen, substituted or unsubstituted C<com:Sub>1-6< / com:Sub> alkyl, or substituted or unsubstituted C<com:Sub>3-8< / com:Sub> cycloalkyl; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[14] (iii) <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics>< / com:Math> are each independently hydrogen, halogen, substituted or unsubstituted <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, or substituted or unsubstituted C<com:Sub>3-8< / com:Sub> cycloalkyl; R<com:Sub>5< / com:Sub> and R<com:Sub>6< / com:Sub> form together with the carbon atom adjacent thereto a substituted or unsubstituted <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[15] (iv) <com:Math><semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> form together with the carbon atom adjacent thereto a substituted or unsubstituted C<com:Sub>3-8< / com:Sub> cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; R<com:Sub>3< / com:Sub> and R<com:Sub>6< / com:Sub> are each independently hydrogen, halogen, substituted or unsubstituted <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, or substituted or unsubstituted <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; 16 B is-L-R<com:Sub>0< / com:Sub>, wherein, <com:Math><semantics>17<annotation encoding="application / x-tex">17< / annotation>< / semantics>< / com:Math> R<com:Sub>0< / com:Sub> is substituted or unsubstituted C<com:Sub>6-14< / com:Sub> aryl, substituted or unsubstituted 5- to 14-membered heteroaryl or substituted or unsubstituted 5- to 14-membered heterocycloalkyl; the "substituted" in R<com:Sub>0< / com:Sub> means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[18] L is a bond, <com:Math><semantics>−(CR11R12)t1−(CR21R22)t2−(CR31R32)t3−(CR41R42)t4−(O)t5<annotation encoding="application / x-tex">-(CR_{11}R_{12})_{t1}-(CR_{21}R_{22})_{t2}-(CR_{31}R_{32})_{t3}-(CR_{41}R_{42})_{t4}-(O)_{t5}< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>−(CR13R14)t1<annotation encoding="application / x-tex">-(CR_{13}R_{14})_{t1}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(CR23R24)t2<annotation encoding="application / x-tex">(CR_{23}R_{24})_{t2}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(NR33)t3<annotation encoding="application / x-tex">(NR_{33})_{t3}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CR43R44)t4<annotation encoding="application / x-tex">(CR_{43}R_{44})_{t4}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(O)t5<annotation encoding="application / x-tex">(O)_{t5}< / annotation>< / semantics>< / com:Math>-, wherein t1, t2, t3, t4 and t5 are each independently 0 or 1; 19 the definition for <com:Math><semantics>R11<annotation encoding="application / x-tex">R_{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R12<annotation encoding="application / x-tex">R_{12}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R21<annotation encoding="application / x-tex">R_{21}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R22<annotation encoding="application / x-tex">R_{22}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R31<annotation encoding="application / x-tex">R_{31}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R32<annotation encoding="application / x-tex">R_{32}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R41<annotation encoding="application / x-tex">R_{41}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R42<annotation encoding="application / x-tex">R_{42}< / annotation>< / semantics>< / com:Math> are selected from one of the following groups:

[20] (a2) <com:Math><semantics>|21|R11<annotation encoding="application / x-tex">|21|R_{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R12<annotation encoding="application / x-tex">R_{12}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R41<annotation encoding="application / x-tex">R_{41}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R42<annotation encoding="application / x-tex">R_{42}< / annotation>< / semantics>< / com:Math> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl;

[22] R<com:Sub>21< / com:Sub>, R<com:Sub>22< / com:Sub>, R<com:Sub>31< / com:Sub> and R<com:Sub>32< / com:Sub> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl;

[23] (b2) <com:Math><semantics>

[24] R11<annotation encoding="application / x-tex">

[24] R_{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R12<annotation encoding="application / x-tex">R_{12}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R41<annotation encoding="application / x-tex">R_{41}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R42<annotation encoding="application / x-tex">R_{42}< / annotation>< / semantics>< / com:Math> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; <com:Math><semantics>

[25] R21<annotation encoding="application / x-tex">

[25] R_{21}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R22<annotation encoding="application / x-tex">R_{22}< / annotation>< / semantics>< / com:Math> form together with the carbon atom adjacent thereto a substituted or unsubstituted C<com:Sub>3-8< / com:Sub> cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; 26 R<com:Sub>31< / com:Sub> and R<com:Sub>32< / com:Sub> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl;

[27] (c2) <com:Math><semantics>|28|R11<annotation encoding="application / x-tex">|28|R_{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R12<annotation encoding="application / x-tex">R_{12}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R41<annotation encoding="application / x-tex">R_{41}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R42<annotation encoding="application / x-tex">R_{42}< / annotation>< / semantics>< / com:Math> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl;

[29] <com:Math><semantics>R21<annotation encoding="application / x-tex">R_{21}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R22<annotation encoding="application / x-tex">R_{22}< / annotation>< / semantics>< / com:Math> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; <com:Math><semantics>30R31<annotation encoding="application / x-tex">30 R_{31}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R32<annotation encoding="application / x-tex">R_{32}< / annotation>< / semantics>< / com:Math> form together with the carbon atom adjacent thereto a substituted or unsubstituted C<com:Sub>3-8< / com:Sub> cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[31] (d2) <com:Math><semantics>

[32] R11<annotation encoding="application / x-tex">

[32] R_{11}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R12<annotation encoding="application / x-tex">R_{12}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R41<annotation encoding="application / x-tex">R_{41}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R42<annotation encoding="application / x-tex">R_{42}< / annotation>< / semantics>< / com:Math> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; 33 R<com:Sub>22< / com:Sub> and R<com:Sub>32< / com:Sub> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; 34 R<com:Sub>21< / com:Sub> and R<com:Sub>31< / com:Sub> form together with the atom adjacent thereto a substituted or unsubstituted C<com:Sub>3-8< / com:Sub> cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[35] (e2) <com:Math><semantics>|36|R12<annotation encoding="application / x-tex">|36|R_{12}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R41<annotation encoding="application / x-tex">R_{41}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R42<annotation encoding="application / x-tex">R_{42}< / annotation>< / semantics>< / com:Math> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; <com:Math><semantics>

[37] R21<annotation encoding="application / x-tex">

[37] R_{21}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R22<annotation encoding="application / x-tex">R_{22}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R32<annotation encoding="application / x-tex">R_{32}< / annotation>< / semantics>< / com:Math> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; <com:Math><semantics>38R11<annotation encoding="application / x-tex">38R_{11}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R31<annotation encoding="application / x-tex">R_{31}< / annotation>< / semantics>< / com:Math> form together with the atom adjacent thereto a substituted or unsubstituted <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; 39 the definition for R<com:Sub>13< / com:Sub>, R<com:Sub>14< / com:Sub>, R<com:Sub>23< / com:Sub>, R<com:Sub>24< / com:Sub>, R<com:Sub>33< / com:Sub>, R<com:Sub>43< / com:Sub> and R<com:Sub>44< / com:Sub> are selected from one of the following groups:

[40] (a3)

[41] R<com:Sub>13< / com:Sub>, R<com:Sub>14< / com:Sub>, R<com:Sub>23< / com:Sub>, R<com:Sub>24< / com:Sub>, R<com:Sub>43< / com:Sub> and R<com:Sub>44< / com:Sub> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; <com:Math><semantics>|42|R33<annotation encoding="application / x-tex">|42|R_{33}< / annotation>< / semantics>< / com:Math> is hydrogen, deuterium, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl;

[43] (b3) <com:Math><semantics>

[44] R13<annotation encoding="application / x-tex">

[44] R_{13}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R14<annotation encoding="application / x-tex">R_{14}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R43<annotation encoding="application / x-tex">R_{43}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R44<annotation encoding="application / x-tex">R_{44}< / annotation>< / semantics>< / com:Math> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; 45 R<com:Sub>23< / com:Sub> and R<com:Sub>24< / com:Sub> form together with the carbon atom adjacent thereto a substituted or unsubstituted C<com:Sub>3-8< / com:Sub> cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[46] <com:Math><semantics>R33<annotation encoding="application / x-tex">R_{33}< / annotation>< / semantics>< / com:Math> is hydrogen, deuterium, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl;

[47] (c3)

[48] R<com:Sub>13< / com:Sub>, R<com:Sub>14< / com:Sub>, R<com:Sub>23< / com:Sub>, R<com:Sub>43< / com:Sub> and R<com:Sub>44< / com:Sub> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl;

[49] R<com:Sub>24< / com:Sub> and R<com:Sub>33< / com:Sub> form together with the atom adjacent thereto a substituted or unsubstituted 3- to 6- membered nitrogen-containing heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[50] (d3)

[51] R<com:Sub>13< / com:Sub>, R<com:Sub>23< / com:Sub>, R<com:Sub>24< / com:Sub>, R<com:Sub>43< / com:Sub> and R<com:Sub>44< / com:Sub> are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; <com:Math><semantics>

[52] R14<annotation encoding="application / x-tex">

[52] R_{14}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R33<annotation encoding="application / x-tex">R_{33}< / annotation>< / semantics>< / com:Math> form together with the atom adjacent thereto a substituted or unsubstituted 3- to 6- membered nitrogen-containing heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[53] A is

[54] (i) substituted or unsubstituted 5- or 6-membered monocyclic heteroaryl, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[55] (ii) substituted or unsubstituted 8- to 10-membered bicyclic heteroaryl, wherein the 8- to 10- membered bicyclic heteroaryl is formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[56] (iii) substituted or unsubstituted 9- or 10-membered bicyclic heteroaryl; the 9- or 10-membered bicyclic heteroaryl is formed by fusing a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring; wherein the 5- or 6-membered monocyclic heteroaryl ring is selected from: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]

[57] wherein the attached two carbon atoms represented by "\cdots" are adjacent pairs of carbon atoms shared when fused with other rings;

[58] the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S;

[59] (iv) substituted or unsubstituted 8- to 10-membered bicyclic heteroaryl; the 8- to 10-membered bicyclic heteroaryl is formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; or

[60] (v) substituted or unsubstituted benzothiazole, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S';

[61] in the above groups, the substituents from group S are selected from deuterium, halogen, nitro, oxo, <com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−haloC1−6<annotation encoding="application / x-tex">-halo\ C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−deuteratedC1−6<annotation encoding="application / x-tex">-deuterated\ C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−S−C1−6<annotation encoding="application / x-tex">-S-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−S−haloC1−6<annotation encoding="application / x-tex">-S-halo\ C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1Rb1)u−1<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u-1}< / annotation>< / semantics>< / com:Math> cyano, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>- halo C<com:Sub>1-6< / com:Sub> alkyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-deuterated C<com:Sub>1-6< / com:Sub> alkoxy, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-deuterated C<com:Sub>1-6< / com:Sub> alkyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>- 3- to 6-membered heterocycloalkyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-C<com:Sub>3-8< / com:Sub> cycloalkyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-phenyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>- 5- or 6-membered monocyclic heteroaryl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-O- <com:Math><semantics>(CRa2Rb2)v−C3−8<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_v-C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−(CRa1Rb1)u−O−(CRa2Rb2)v−3−<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u-O-(CR_{a2}R_{b2})_v-3-< / annotation>< / semantics>< / com:Math> to 6-membered heterocycloalkyl, - <com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_{u}< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_{v}< / annotation>< / semantics>< / com:Math>-phenyl, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_{u}< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_{v}< / annotation>< / semantics>< / com:Math>-5- or 6-membered monocyclic heteroaryl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-S-<com:Math><semantics>−(CRa2Rb2)v<annotation encoding="application / x-tex">-(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-SO<com:Sub>2< / com:Sub>-<com:Math><semantics>−(CRa2Rb2)v<annotation encoding="application / x-tex">-(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-O- <com:Math><semantics>C(O)NRa0Rb0<annotation encoding="application / x-tex">C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>O−(CRa2Rb2)v<annotation encoding="application / x-tex">O-(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>O−(CRa2Rb2)v<annotation encoding="application / x-tex">O-(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>(CRa1Rb1)u−SO2C1−6<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_{u}-SO_{2}C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1Rb1)u−SO2NRa0Rb0<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-SO_{2}NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u−C(O)NRa0Rb0<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u−C(O)NRa0Rb0<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math> phenyl, <com:Math><semantics>−(CRa1Rb1)u−C(O)C1−6<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u-C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)OC1−6<annotation encoding="application / x-tex">-C(O)OC_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−(CRa2Rb2)v−hydroxyl<annotation encoding="application / x-tex">-C(O)-(CR_{a2}R_{b2})_v-hydroxyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−(CRa2Rb2)v−hydroxyl<annotation encoding="application / x-tex">-C(O)-(CR_{a2}R_{b2})_v-hydroxyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−(CRa2Rb2)v−hydroxyl<annotation encoding="application / x-tex">-C(O)-(CR_{a2}R_{b2})_v-hydroxyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−C(O)−(CRa2Rb2)v−hydroxyl<annotation encoding="application / x-tex">-C(O)-(CR_{a2}R_{b2})_v-hydroxyl< / annotation>< / semantics>< / com:Math>, <Formule mathématique disponible dans le document PDF, Math available in the PDF document display="block">(CR_{a1}R_{b1})_{u}-NR_{a0}R_{b0},\quad -NR_{a0}C(O)-C_{1-6}\quad alkyl,\quad -NR_{a0}C(O)-deuterated\quad C_{1-6}\quad alkyl,\quad -NR_{a0}C(O)-deuterated\quad C_{1-6}\quad alkyl,\quad -NR_{a0}C(O)-deuterated\quad C_{1-6}\quad alkyl,\quad -NR_{a0}C(O)-deuterated\quad C_{ <com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>O<annotation encoding="application / x-tex">O< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)C1−6<annotation encoding="application / x-tex">C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>O−(CRa2Rb2)v<annotation encoding="application / x-tex">O-(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−NRa0C(O)−C3−8<annotation encoding="application / x-tex">-NR_{a0}C(O)-C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−NRa0C(O)−(CRa1Rb1)u−NRa0Rb0<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CR_{a1}R_{b1})_u-NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>−NRa0C(O)−(CRa1Rb1)u<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math> halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, wherein the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, C<com:Sub>1-3< / com:Sub> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> are each independently hydrogen or C<com:Sub>1-3< / com:Sub> alkyl; or R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen- containing heterocycloalkyl, wherein the 3- to 8-membered nitrogen-containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or C<com:Sub>1-3< / com:Sub> alkyl; R<com:Sub>a1< / com:Sub>, R<com:Sub>b1< / com:Sub>, R<com:Sub>a2< / com:Sub> and R<com:Sub>b2< / com:Sub> are the same or different, and are each independently hydrogen, hydroxyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl;

[62] in the above groups, the substituents from group S' are selected from deuterium, halogen, nitro, oxo, <com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -deuterated <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -S-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -S-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, - <com:Math><semantics>(CRa1′Rb1′)u′<annotation encoding="application / x-tex">(CR_{a1}'R_{b1}')_{u'}< / annotation>< / semantics>< / com:Math>-cyano, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u'}< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u'}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u'}< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, -(CR<com:Sub>a1< / com:Sub>'R<com:Sub>b1< / com:Sub>')<com:Sub>u< / com:Sub>'-halo C<com:Sub>1-6< / com:Sub> alkyl, -(CR<com:Sub>a1< / com:Sub>'R<com:Sub>b1< / com:Sub>')<com:Sub>u< / com:Sub>'-3- to 6-membered heterocycloalkyl, - (CR<com:Sub>a1< / com:Sub>'R<com:Sub>b1< / com:Sub>')<com:Sub>u< / com:Sub>'-C<com:Sub>3-8< / com:Sub> cycloalkyl, -(CR<com:Sub>a1< / com:Sub>'R<com:Sub>b1< / com:Sub>')<com:Sub>u< / com:Sub>'-phenyl, -(CR<com:Sub>a1< / com:Sub>'R<com:Sub>b1< / com:Sub>')<com:Sub>u< / com:Sub>'-5- or 6-membered monocyclic heteroaryl, <com:Math><semantics>−(CRa1′Rb1′)u′−O−(CRa2′Rb2′)v′−halo<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-halo< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C1−<annotation encoding="application / x-tex">C_{1-}< / annotation>< / semantics>< / com:Math> 6alkyl, <com:Math><semantics>−(CRa1′Rb1′)u′−O−(CRa2′Rb2′)v′−C3−8<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl, -(CR<com:Sub>a1< / com:Sub>'R<com:Sub>b1< / com:Sub>')<com:Sub>u< / com:Sub>'-O-(CR<com:Sub>a2< / com:Sub>'R<com:Sub>b2< / com:Sub>')<com:Sub>v< / com:Sub>'-3- to 6-membered heterocycloalkyl, -(CR<com:Sub>a1< / com:Sub>'R<com:Sub>b1< / com:Sub>')<com:Sub>u< / com:Sub>'-O- (CR<com:Sub>a2< / com:Sub>'R<com:Sub>b2< / com:Sub>')<com:Sub>v< / com:Sub>-phenyl, -(CR<com:Sub>a1< / com:Sub>'R<com:Sub>b1< / com:Sub>')<com:Sub>u< / com:Sub>'-O-(CR<com:Sub>a2< / com:Sub>'R<com:Sub>b2< / com:Sub>')<com:Sub>v< / com:Sub>'-5- or 6-membered monocyclic heteroaryl, - <Formule mathématique disponible dans le document PDF, Math available in the PDF document>(CR_{a1}'R_{b1}')_{u}-S-(CR_{a2}'R_{b2}')_{v}'-phenyl, -(CR_{a1}'R_{b1}')_{u}'-SO_{2}-(CR_{a2}'R_{b2}')_{v}'-phenyl, -(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-phenyl, -(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v <com:Math><semantics>C(O)NRa0′Rb0′,−(CRa1′Rb1′)u′−O−(CRa2′Rb2′)v′−C1−6<annotation encoding="application / x-tex">C(O)NR_{a0}'R_{b0}', -(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1′Rb1′)u′−O−(CRa2′Rb2′)v′−C1−6<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-C_{1-6}< / annotation>< / semantics>< / com:Math> hydroxyl, <com:Math><semantics>−(CRa1′Rb1′)u′−SO2C1−6<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-SO_{2}C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1′Rb1′)u′−SO2NRa0′Rb0′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-SO_{2}NR_{a0}'R_{b0}'< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1′Rb1′)u′−<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)NRa0′Rb0′<annotation encoding="application / x-tex">C(O)NR_{a0}'R_{b0}'< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1′Rb1′)u′−C(O)<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-C(O)< / annotation>< / semantics>< / com:Math> phenyl, <com:Math><semantics>−(CRa1′Rb1′)u′−C(O)C1−6<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)OC1−6<annotation encoding="application / x-tex">-C(O)OC_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, and C(O)-(CR<com:Sub>a2< / com:Sub>'R<com:Sub>b2< / com:Sub>')<com:Sub>v< / com:Sub>'-hydroxyl, wherein the C<com:Sub>3-8< / com:Sub> cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u' and v' are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub>' and R<com:Sub>b0< / com:Sub>' are each independently hydrogen or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; or <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math>' and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>' form together with the nitrogen atom adjacent theretoa 3- to 8-membered nitrogen-containing heterocycloalkyl, wherein the 3- to 8-membered nitrogen- containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or C<com:Sub>1-3< / com:Sub> alkyl; R<com:Sub>a1< / com:Sub>', R<com:Sub>b1< / com:Sub>', <com:Math><semantics>Ra2<annotation encoding="application / x-tex">R_{a2}< / annotation>< / semantics>< / com:Math>' and <com:Math><semantics>Rb2<annotation encoding="application / x-tex">R_{b2}< / annotation>< / semantics>< / com:Math>' are the same or different, and are each independently hydrogen, hydroxyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl.

[63] In an embodiment of the present disclosure, when A is substituted or unsubstituted 5- or 6- membered monocyclic heteroaryl, the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine and pyrazine.

[64] In an embodiment of the present disclosure, with regard to A, in the 8- to 10-membered bicyclic heteroaryl formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6- membered monocyclic heteroaryl ring, the 5- or 6-membered monocyclic heteroaryl ring is selected from: [Image disponible dans le document PDF, Image available in the PDF document]

[65] wherein the attached two carbon atoms represented by "\" are adjacent pairs of carbon atoms shared when fused with other rings.

[66] In an embodiment of the present disclosure, with regard to A, the 8- to 10-membered bicyclic heteroaryl formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6- membered monocyclic heteroaryl ring has a structure represented by formula (A1), formula (A2) or formula (A3): [Image disponible dans le document PDF, Image available in the PDF document] ,

[67] wherein <com:Math><semantics>Z1<annotation encoding="application / x-tex">Z_1< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRZ1<annotation encoding="application / x-tex">CR_{Z_1}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>Z2<annotation encoding="application / x-tex">Z_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>NRZ2<annotation encoding="application / x-tex">NR_{Z_2}< / annotation>< / semantics>< / com:Math> or O; <com:Math><semantics>Z3<annotation encoding="application / x-tex">Z_3< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRZ3<annotation encoding="application / x-tex">CR_{Z_3}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>Z4<annotation encoding="application / x-tex">Z_4< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRZ4<annotation encoding="application / x-tex">CR_{Z_4}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>Z5<annotation encoding="application / x-tex">Z_5< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRZ5<annotation encoding="application / x-tex">CR_{Z_5}< / annotation>< / semantics>< / com:Math>; Z<com:Sub>6< / com:Sub> is N or CR<com:Sub>Z6< / com:Sub>; Z<com:Sub>3< / com:Sub>, Z<com:Sub>4< / com:Sub>, Z<com:Sub>5< / com:Sub> and Z<com:Sub>6< / com:Sub> are not N at the same time; and at least one of Z<com:Sub>3< / com:Sub>, Z<com:Sub>4< / com:Sub>, Z<com:Sub>5< / com:Sub> and Z<com:Sub>6< / com:Sub> is N;

[68] Y<com:Sub>1< / com:Sub> is N or CR<com:Sub>Y1< / com:Sub>; Y<com:Sub>2< / com:Sub> is N or CR<com:Sub>Y2< / com:Sub>; Y<com:Sub>3< / com:Sub> is N or CR<com:Sub>Y3< / com:Sub>; Y<com:Sub>4< / com:Sub> is N or CR<com:Sub>Y4< / com:Sub>; Y<com:Sub>5< / com:Sub> is N or CR<com:Sub>Y5< / com:Sub>; Y<com:Sub>6< / com:Sub> is N or CR<com:Sub>Y6< / com:Sub>; Y<com:Sub>7< / com:Sub> is N or CR<com:Sub>Y7< / com:Sub>; Y<com:Sub>3< / com:Sub>, Y<com:Sub>4< / com:Sub>, Y<com:Sub>5< / com:Sub>, Y<com:Sub>6< / com:Sub> and Y<com:Sub>7< / com:Sub> are not N at the same time; and at least one of Y<com:Sub>1< / com:Sub>, <com:Math><semantics>Y2,Y3,Y4,Y5,Y6 and Y7 is N;<annotation encoding="application / x-tex">Y_2, Y_3, Y_4, Y_5, Y_6 \text{ and } Y_7 \text{ is } N;< / annotation>< / semantics>< / com:Math>

[69] <com:Math><semantics>U1<annotation encoding="application / x-tex">U_1< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRU1<annotation encoding="application / x-tex">CR_{U1}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U2<annotation encoding="application / x-tex">U_2< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRU2<annotation encoding="application / x-tex">CR_{U2}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U3<annotation encoding="application / x-tex">U_3< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRU3<annotation encoding="application / x-tex">CR_{U3}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U4<annotation encoding="application / x-tex">U_4< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRU4<annotation encoding="application / x-tex">CR_{U4}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U5<annotation encoding="application / x-tex">U_5< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRU5<annotation encoding="application / x-tex">CR_{U5}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U6<annotation encoding="application / x-tex">U_6< / annotation>< / semantics>< / com:Math> is N or CR<com:Sub>U6< / com:Sub>; U<com:Sub>7< / com:Sub> is N or CR<com:Sub>U7< / com:Sub>; U<com:Sub>8< / com:Sub> is N or CR<com:Sub>U8< / com:Sub>; U<com:Sub>4< / com:Sub>, U<com:Sub>5< / com:Sub>, U<com:Sub>6< / com:Sub>, U<com:Sub>7< / com:Sub> and U<com:Sub>8< / com:Sub> are not N at the same time; and at least one of <com:Math><semantics>U1<annotation encoding="application / x-tex">U_1< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>U2<annotation encoding="application / x-tex">U_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>U3<annotation encoding="application / x-tex">U_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>U4<annotation encoding="application / x-tex">U_4< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>U5<annotation encoding="application / x-tex">U_5< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>U6<annotation encoding="application / x-tex">U_6< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>U7<annotation encoding="application / x-tex">U_7< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>U8<annotation encoding="application / x-tex">U_8< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>N<annotation encoding="application / x-tex">N< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>

[70] RZ0,RY0,RZ1,RZ2,RZ3,RZ4,RZ5,RZ6,RY1,RY2,RY3,RY4,RY5,RY6,RY7,RU1,RU2,RU3,RU4,<annotation encoding="application / x-tex">

[70] R_{Z0}, R_{Y0}, R_{Z1}, R_{Z2}, R_{Z3}, R_{Z4}, R_{Z5}, R_{Z6}, R_{Y1}, R_{Y2}, R_{Y3}, R_{Y4}, R_{Y5}, R_{Y6}, R_{Y7}, R_{U1}, R_{U2}, R_{U3}, R_{U4},< / annotation>< / semantics>< / com:Math> <com:Math><semantics>RU5<annotation encoding="application / x-tex">R_{U5}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>RU6<annotation encoding="application / x-tex">R_{U6}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>RU7<annotation encoding="application / x-tex">R_{U7}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>RU8<annotation encoding="application / x-tex">R_{U8}< / annotation>< / semantics>< / com:Math> are each independently hydrogen or the substituents from group S.

[71] In an embodiment of the present disclosure the 9- or 10-membered bicyclic heteroaryl said in A formed by fusing a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring has a structure represented by formula (A4): [Image disponible dans le document PDF, Image available in the PDF document]

[72] wherein <com:Math><semantics>W1<annotation encoding="application / x-tex">W_1< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRW1<annotation encoding="application / x-tex">CR_{W1}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>W2<annotation encoding="application / x-tex">W_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>NRW2<annotation encoding="application / x-tex">NR_{W2}< / annotation>< / semantics>< / com:Math> or O; n is 1, 2 or 3; <com:Math><semantics>RW0<annotation encoding="application / x-tex">R_{W0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>RW1<annotation encoding="application / x-tex">R_{W1}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>RW2<annotation encoding="application / x-tex">R_{W2}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>RW3<annotation encoding="application / x-tex">R_{W3}< / annotation>< / semantics>< / com:Math> are each independently hydrogen or the substituents from group S.

[73] In an embodiment of the present disclosure the 8- to 10-membered bicyclic heteroaryl said in A formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring has a structure represented by formula (A5): [Image disponible dans le document PDF, Image available in the PDF document] > 74 wherein G<com:Sub>1< / com:Sub> is N or CR<com:Sub>G1< / com:Sub>; G<com:Sub>2< / com:Sub> is N or CR<com:Sub>G2< / com:Sub>; G<com:Sub>3< / com:Sub> is N or CR<com:Sub>G3< / com:Sub>; G<com:Sub>4< / com:Sub> is NR<com:Sub>G4a< / com:Sub>, O or CR<com:Sub>G4b< / com:Sub>R<com:Sub>G4c< / com:Sub>; G<com:Sub>5< / com:Sub> is NR<com:Sub>G5a< / com:Sub>, O or CR<com:Sub>G5b< / com:Sub>R<com:Sub>G5c< / com:Sub>; G<com:Sub>6< / com:Sub> is NR<com:Sub>G6a< / com:Sub>, O or CR<com:Sub>G6b< / com:Sub>R<com:Sub>G6c< / com:Sub>; G<com:Sub>7< / com:Sub> is NR<com:Sub>G7a< / com:Sub>, O or CR<com:Sub>G7b< / com:Sub>R<com:Sub>G7c< / com:Sub>; at least one of G<com:Sub>3< / com:Sub>, G<com:Sub>4< / com:Sub>, G<com:Sub>5< / com:Sub>, G<com:Sub>6< / com:Sub> and G<com:Sub>7< / com:Sub> is N; and the ring part of -G<com:Sub>3< / com:Sub>-G<com:Sub>4< / com:Sub>-G<com:Sub>5< / com:Sub>-G<com:Sub>6< / com:Sub>-G<com:Sub>7< / com:Sub>- does not comprise -O-O-, -O- N- or-N-N-; R<com:Sub>G0< / com:Sub>, R<com:Sub>G1< / com:Sub>, R<com:Sub>G2< / com:Sub>, R<com:Sub>G3< / com:Sub>, R<com:Sub>G4a< / com:Sub>, R<com:Sub>G4b< / com:Sub>, R<com:Sub>G4c< / com:Sub>, R<com:Sub>G5a< / com:Sub>, R<com:Sub>G5b< / com:Sub>, R<com:Sub>G5c< / com:Sub>, R<com:Sub>G6a< / com:Sub>, R<com:Sub>G6b< / com:Sub>, R<com:Sub>G6c< / com:Sub>, R<com:Sub>G7a< / com:Sub>, R<com:Sub>G7b< / com:Sub> and <com:Math><semantics>RG7c<annotation encoding="application / x-tex">R_{G7c}< / annotation>< / semantics>< / com:Math> are each independently hydrogen or the substituents from group S.

[75] In an embodiment of the present disclosure, with regard to A, the benzothiazole has a structure represented by formula (A6): [Image disponible dans le document PDF, Image available in the PDF document] 7

[76] wherein <com:Math><semantics>RE0<annotation encoding="application / x-tex">R_{E0}< / annotation>< / semantics>< / com:Math> is hydrogen or the substituents from group S'.

[77] In an embodiment of the present disclosure, <com:Math><semantics>Z1<annotation encoding="application / x-tex">Z_1< / annotation>< / semantics>< / com:Math> is N; <com:Math><semantics>Z2<annotation encoding="application / x-tex">Z_2< / annotation>< / semantics>< / com:Math> is NR<com:Sub>Z2< / com:Sub> or O.

[78] In an embodiment of the present disclosure, <com:Math><semantics>Y1<annotation encoding="application / x-tex">Y_1< / annotation>< / semantics>< / com:Math> is N; <com:Math><semantics>Y2<annotation encoding="application / x-tex">Y_2< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRY2<annotation encoding="application / x-tex">CR_{Y_2}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>Y3<annotation encoding="application / x-tex">Y_3< / annotation>< / semantics>< / com:Math> is N; <com:Math><semantics>Y4<annotation encoding="application / x-tex">Y_4< / annotation>< / semantics>< / com:Math> is N or <com:Math><semantics>CRY4<annotation encoding="application / x-tex">CR_{Y_4}< / annotation>< / semantics>< / com:Math>; Y<com:Sub>5< / com:Sub> is CR<com:Sub>Y5< / com:Sub>; Y<com:Sub>6< / com:Sub> is CR<com:Sub>Y6< / com:Sub>; Y<com:Sub>7< / com:Sub> is CR<com:Sub>Y7< / com:Sub>.

[79] In an embodiment of the present disclosure, <com:Math><semantics>Y1<annotation encoding="application / x-tex">Y_1< / annotation>< / semantics>< / com:Math> is N; <com:Math><semantics>Y2<annotation encoding="application / x-tex">Y_2< / annotation>< / semantics>< / com:Math> is N or CH; <com:Math><semantics>Y3<annotation encoding="application / x-tex">Y_3< / annotation>< / semantics>< / com:Math> is N; <com:Math><semantics>Y4<annotation encoding="application / x-tex">Y_4< / annotation>< / semantics>< / com:Math> is N or CH; <com:Math><semantics>Y5<annotation encoding="application / x-tex">Y_5< / annotation>< / semantics>< / com:Math> is CH; Y<com:Sub>6< / com:Sub> is CH; Y<com:Sub>7< / com:Sub> is CH. 80 In an embodiment of the present disclosure, U<com:Sub>1< / com:Sub> is CR<com:Sub>U1< / com:Sub>; U<com:Sub>2< / com:Sub> is CR<com:Sub>U2< / com:Sub>; U<com:Sub>3< / com:Sub> is CR<com:Sub>U3< / com:Sub>; U<com:Sub>4< / com:Sub> is N; U<com:Sub>5< / com:Sub> is N; <com:Math><semantics>U6<annotation encoding="application / x-tex">U_6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRU6<annotation encoding="application / x-tex">CR_{U6}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U7<annotation encoding="application / x-tex">U_7< / annotation>< / semantics>< / com:Math> is N; <com:Math><semantics>U8<annotation encoding="application / x-tex">U_8< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRU8<annotation encoding="application / x-tex">CR_{U8}< / annotation>< / semantics>< / com:Math>.

[81] In an embodiment of the present disclosure, <com:Math><semantics>U1<annotation encoding="application / x-tex">U_1< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRU1<annotation encoding="application / x-tex">CR_{U1}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U2<annotation encoding="application / x-tex">U_2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CH<annotation encoding="application / x-tex">CH< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U3<annotation encoding="application / x-tex">U_3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CH<annotation encoding="application / x-tex">CH< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U4<annotation encoding="application / x-tex">U_4< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>N<annotation encoding="application / x-tex">N< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U5<annotation encoding="application / x-tex">U_5< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>N<annotation encoding="application / x-tex">N< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>U6<annotation encoding="application / x-tex">U_6< / annotation>< / semantics>< / com:Math> is CH; <com:Math><semantics>U7<annotation encoding="application / x-tex">U_7< / annotation>< / semantics>< / com:Math> is N; <com:Math><semantics>U8<annotation encoding="application / x-tex">U_8< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRU8<annotation encoding="application / x-tex">CR_{U8}< / annotation>< / semantics>< / com:Math>. 82 In an embodiment of the present disclosure, G<com:Sub>1< / com:Sub> is N; G<com:Sub>2< / com:Sub> is N; G<com:Sub>3< / com:Sub> is N; G<com:Sub>4< / com:Sub> is CR<com:Sub>G4b< / com:Sub>R<com:Sub>G4c< / com:Sub>; G<com:Sub>5< / com:Sub> is <com:Math><semantics>CRG5bRG5c<annotation encoding="application / x-tex">CR_{G5b}R_{G5c}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>G6<annotation encoding="application / x-tex">G_6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>NRG6a<annotation encoding="application / x-tex">NR_{G6a}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>G7<annotation encoding="application / x-tex">G_7< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRG7bRG7c<annotation encoding="application / x-tex">CR_{G7b}R_{G7c}< / annotation>< / semantics>< / com:Math>.

[83] In an embodiment of the present disclosure, G<com:Sub>1< / com:Sub> is N; G<com:Sub>2< / com:Sub> is N; G<com:Sub>3< / com:Sub> is N; G<com:Sub>4< / com:Sub> is CH<com:Sub>2< / com:Sub>; G<com:Sub>5< / com:Sub> is CH<com:Sub>2< / com:Sub>; <com:Math><semantics>G6<annotation encoding="application / x-tex">G_6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>NRG6a<annotation encoding="application / x-tex">NR_{G6a}< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>G7<annotation encoding="application / x-tex">G_7< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CH2<annotation encoding="application / x-tex">CH_2< / annotation>< / semantics>< / com:Math>.

[84] In an embodiment of the present disclosure, R<com:Sub>Z1< / com:Sub>, R<com:Sub>Z3< / com:Sub>, R<com:Sub>Z4< / com:Sub>, R<com:Sub>Z5< / com:Sub> and R<com:Sub>Z6< / com:Sub> are each independently hydrogen, deuterium, halogen, C<com:Sub>1-6< / com:Sub> alkyl, C<com:Sub>1-6< / com:Sub> alkoxy, halo C<com:Sub>1-6< / com:Sub> alkyl or NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>; R<com:Sub>Z2< / com:Sub> is hydrogen, deuterium or <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl. 85 In an embodiment of the present disclosure, R<com:Sub>Y1< / com:Sub>, R<com:Sub>Y2< / com:Sub>, R<com:Sub>Y3< / com:Sub>, R<com:Sub>Y4< / com:Sub>, R<com:Sub>Y5< / com:Sub>, R<com:Sub>Y6< / com:Sub> and R<com:Sub>Y7< / com:Sub> are each independently hydrogen, deuterium, halogen, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>NRa0Rb0<annotation encoding="application / x-tex">NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>.

[86] In an embodiment of the present disclosure, the substituents from group S are each independently selected from halogen, nitro, oxo, <com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -deuterated <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−S−C1−6<annotation encoding="application / x-tex">-S-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−S<annotation encoding="application / x-tex">-S< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-cyano, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-3- to 6-membered heterocycloalkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−1<annotation encoding="application / x-tex">C_{3-1}< / annotation>< / semantics>< / com:Math> scycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-5- or 6-membered monocyclic heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>- halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-3- to 6-membered heterocycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-5- or 6-membered monocyclic heteroaryl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-S-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-SO<com:Sub>2< / com:Sub>-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-C(O)NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, - <com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-C<com:Sub>1-6< / com:Sub> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>SO2NRa0Rb0<annotation encoding="application / x-tex">SO_2NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)u−C(O)NRa0Rb0<annotation encoding="application / x-tex">-(CH_2)_u-C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)u−C(O)C1−6<annotation encoding="application / x-tex">-(CH_2)_u-C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)OC1−6<annotation encoding="application / x-tex">-C(O)OC_{1-6}< / annotation>< / semantics>< / com:Math>alkyl, <com:Math><semantics>−C(O)−(CH2)v−C(O)<annotation encoding="application / x-tex">-C(O)-(CH_2)_v-C(O)< / annotation>< / semantics>< / com:Math> hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-deuterated C<com:Sub>1-6< / com:Sub>alkyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_{u}< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math>cycloalkyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_{u}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>NRa0Rb0<annotation encoding="application / x-tex">NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_{u}< / annotation>< / semantics>< / com:Math>- hydroxyl, and-<com:Math><semantics>NRa0C(O)<annotation encoding="application / x-tex">NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, wherein the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo C<com:Sub>3-6< / com:Sub> cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> are each independently hydrogen or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; or <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl, wherein the 3- to 8-membered nitrogen-containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math>alkyl; <com:Math><semantics>Ra1<annotation encoding="application / x-tex">R_{a1}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>Rb1<annotation encoding="application / x-tex">R_{b1}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>Ra2<annotation encoding="application / x-tex">R_{a2}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb2<annotation encoding="application / x-tex">R_{b2}< / annotation>< / semantics>< / com:Math> are the same or different, and are each independently hydrogen, hydroxyl, <com:Math><semantics>C1−<annotation encoding="application / x-tex">C_{1-}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>3<annotation encoding="application / x-tex">_3< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl.

[87] In an embodiment of the present disclosure, the substituents from group S are each independently selected from deuterium, halogen, nitro, oxo, -C<com:Sub>1-3< / com:Sub> alkyl, -halo C<com:Sub>1-3< / com:Sub> alkyl, -deuterated <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−S−C1−3<annotation encoding="application / x-tex">-S-C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−S−haloC1−3<annotation encoding="application / x-tex">-S-halo\ C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-cyano, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-deuterated <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-deuterated <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-3- to 6-membered heterocycloalkyl, - <com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_{u}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}< / annotation>< / semantics>< / com:Math>-5- or 6-membered monocyclic heteroaryl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl, - (CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CR<com:Sub>a2< / com:Sub>R<com:Sub>b2< / com:Sub>)<com:Sub>v< / com:Sub>-3- to 6-membered heterocycloalkyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CR<com:Sub>a2< / com:Sub>R<com:Sub>b2< / com:Sub>)<com:Sub>v< / com:Sub>-phenyl, - (CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CR<com:Sub>a2< / com:Sub>R<com:Sub>b2< / com:Sub>)<com:Sub>v< / com:Sub>-5- or 6-membered monocyclic heteroaryl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-S-(CR<com:Sub>a2< / com:Sub>R<com:Sub>b2< / com:Sub>)<com:Sub>v< / com:Sub>- phenyl, <com:Math><semantics>−(CRa1Rb1)u−SO2−(CRa2Rb2)v−phenyl,<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-SO_{2}-(CR_{a2}R_{b2})_{v}-phenyl,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CRa1Rb1)u−O−C(O)NRa0Rb0,<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-O-C(O)NR_{a0}R_{b0},< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CRa1Rb1)u−O−C(O)NRa0Rb0,<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-O-C(O)NR_{a0}R_{b0},< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CRa1Rb1)u−O−C(O)NRa0Rb0,<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-O-C(O)NR_{a0}R_{b0},< / annotation>< / semantics>< / com:Math> <Formule mathématique disponible dans le document PDF, Math available in the PDF document>$-(CR_{a1}R_{b1})_{u}-O-C(O)NR_$ <com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math>alkoxy, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>O<annotation encoding="application / x-tex">O< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-hydroxyl, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>SO2C1−3<annotation encoding="application / x-tex">SO_2C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, - <com:Math><semantics>(CRa1Rb1)u−SO2NRa0Rb0<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_{u}-SO_{2}NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u−C(O)NRa0Rb0<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u−C(O)<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-C(O)< / annotation>< / semantics>< / com:Math> 3 alkyl, <com:Math><semantics>−C(O)OC1−3<annotation encoding="application / x-tex">-C(O)OC_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−(CRa2Rb2)v<annotation encoding="application / x-tex">-C(O)-(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, <com:Math><semantics>−NRa0C(O)−C1−3<annotation encoding="application / x-tex">-NR_{a0}C(O)-C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-deuterated <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-O- <com:Math><semantics>(CRa2Rb2)v−C(O)C1−6<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_{v}-C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−NRa0C(O)−(CRa1Rb1)u−O−(CRa2Rb2)v<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CR_{a1}R_{b1})_{u}-O-(CR_{a2}R_{b2})_{v}< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−NRa0C(O)−C3−6<annotation encoding="application / x-tex">-NR_{a0}C(O)-C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>NRa0Rb0<annotation encoding="application / x-tex">NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, wherein the <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> are each independently hydrogen or C<com:Sub>1-3< / com:Sub> alkyl; or R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> form together with the nitrogen atom adjacent thereto a 3- to 6-membered nitrogen-containing heterocycloalkyl, wherein the 3- to 6-membered nitrogen-containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; <com:Math><semantics>Ra1<annotation encoding="application / x-tex">R_{a1}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>Rb1<annotation encoding="application / x-tex">R_{b1}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>Ra2<annotation encoding="application / x-tex">R_{a2}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb2<annotation encoding="application / x-tex">R_{b2}< / annotation>< / semantics>< / com:Math> are the same or different, and are each independently hydrogen, hydroxyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl.

[88] In an embodiment of the present disclosure, the substituents from group S are each independently selected from deuterium, halogen, nitro, oxo, -C<com:Sub>1-3< / com:Sub> alkyl, -halo C<com:Sub>1-3< / com:Sub> alkyl, -deuterated <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−S−C1−3<annotation encoding="application / x-tex">-S-C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−S−C1−3<annotation encoding="application / x-tex">-S-C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-cyano, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>−C1−3<annotation encoding="application / x-tex">-C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-deuterated <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-deuterated C<com:Sub>1-3< / com:Sub> alkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-3- to 6-membered heterocycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-C<com:Sub>3-6< / com:Sub> cycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-phenyl, - (CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-5- or 6-membered monocyclic heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-halo C<com:Sub>1-3< / com:Sub> alkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-O- (CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-C<com:Sub>3-6< / com:Sub> cycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-3- to 6-membered heterocycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>- phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-5- or 6-membered monocyclic heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-S-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-phenyl, - <com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>-SO<com:Sub>2< / com:Sub>-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-phenyl, -<com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-C(O)NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, -<com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-C<com:Sub>1-3< / com:Sub> alkoxy, -<com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>-O- <com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-SO<com:Sub>2< / com:Sub>C<com:Sub>1-3< / com:Sub> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-SO<com:Sub>2< / com:Sub>NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-C(O)NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math> phenyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−C(O)C1−3<annotation encoding="application / x-tex">-C(O)C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)OC1−3<annotation encoding="application / x-tex">-C(O)OC_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−(CH2)v<annotation encoding="application / x-tex">-C(O)-(CH_2)_v< / annotation>< / semantics>< / com:Math> -hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math> -NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, - <com:Math><semantics>NRa0C(O)−C1−3<annotation encoding="application / x-tex">NR_{a0}C(O)-C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-deuterated <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−NRa0C(O)−(CH2)u<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CH_2)_u< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-C(O)C<com:Sub>1-6< / com:Sub> alkyl, -NR<com:Sub>a0< / com:Sub>C(O)-<com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-phenyl, -NR<com:Sub>a0< / com:Sub>C(O)-C<com:Sub>3-6< / com:Sub> cycloalkyl, -NR<com:Sub>a0< / com:Sub>C(O)-(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, and-NR<com:Sub>a0< / com:Sub>C(O)-halo C<com:Sub>1-3< / com:Sub> alkyl, wherein the C<com:Sub>3-6< / com:Sub> cycloalkyl, 3- to 6- membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> are each independently hydrogen or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math>alkyl; or <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> form together with the nitrogen atom adjacent thereto a 3- to 6-membered nitrogen-containing heterocycloalkyl, wherein the 3- to 6- membered nitrogen-containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or C<com:Sub>1-3< / com:Sub> alkyl; R<com:Sub>a1< / com:Sub>, R<com:Sub>b1< / com:Sub>, R<com:Sub>a2< / com:Sub> and R<com:Sub>b2< / com:Sub> are the same or different, and are each independently hydrogen, hydroxyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl. 89 In an embodiment of the present disclosure, the substituents from group S' are selected from halogen, nitro, oxo, -C<com:Sub>1-6< / com:Sub> alkyl, -halo C<com:Sub>1-6< / com:Sub> alkyl, -deuterated C<com:Sub>1-6< / com:Sub> alkyl, -S-C<com:Sub>1-6< / com:Sub> alkyl, -S-halo C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-cyano, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'- halo C<com:Sub>1-6< / com:Sub> alkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-3- to 6-membered heterocycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-C<com:Sub>3-8< / com:Sub> cycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'- phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-5- or 6-membered monocyclic heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-halo C<com:Sub>1-6< / com:Sub> alkyl, - <com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>'-O-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>'-C<com:Sub>3-8< / com:Sub> cycloalkyl, -<com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>'-O-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>'-3- to 6-membered heterocycloalkyl, - (CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-5- or 6-membered monocyclic heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'- S-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-SO<com:Sub>2< / com:Sub>-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-C(O)NR<com:Sub>a0< / com:Sub>'R<com:Sub>b0< / com:Sub>', -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'- <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>O−(CH2)v<annotation encoding="application / x-tex">O-(CH_2)_v< / annotation>< / semantics>< / com:Math>'-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>SO2C1−6<annotation encoding="application / x-tex">SO_2C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>SO2NRa0<annotation encoding="application / x-tex">SO_2NR_{a0}< / annotation>< / semantics>< / com:Math>'<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>' <com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>C(O)NRa0<annotation encoding="application / x-tex">C(O)NR_{a0}< / annotation>< / semantics>< / com:Math>'<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', -<com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>C(O)C1−6<annotation encoding="application / x-tex">C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -<com:Math><semantics>C(O)OC1−6<annotation encoding="application / x-tex">C(O)OC_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, and -<com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa2<annotation encoding="application / x-tex">(CR_{a2}< / annotation>< / semantics>< / com:Math>'<com:Math><semantics>Rb2<annotation encoding="application / x-tex">R_{b2}< / annotation>< / semantics>< / com:Math>')<com:Math><semantics>v<annotation encoding="application / x-tex">_v< / annotation>< / semantics>< / com:Math>'- hydroxyl, wherein the C<com:Sub>3-8< / com:Sub> cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or 6- membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, C<com:Sub>1-3< / com:Sub> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u' and v' are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub>' and R<com:Sub>b0< / com:Sub>' are each independently hydrogen or C<com:Sub>1-3< / com:Sub> alkyl; or R<com:Sub>a0< / com:Sub>' and R<com:Sub>b0< / com:Sub>' form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen- containing heterocycloalkyl, wherein the 3- to 8-membered nitrogen-containing heterocycloalkyl is WSLEGAL\092120\00005\36981746v1 optionally substituted with 1, 2 or 3 halogens or C<com:Sub>1-3< / com:Sub> alkyl; R<com:Sub>a1< / com:Sub>', R<com:Sub>b1< / com:Sub>', R<com:Sub>a2< / com:Sub>' and R<com:Sub>b2< / com:Sub>' are the same or different, and are each independently hydrogen, hydroxyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl. 90 In an embodiment of the present disclosure, the substituents from group S' are selected from deuterium, halogen, nitro, oxo, -C<com:Sub>1-3< / com:Sub> alkyl, -halo C<com:Sub>1-3< / com:Sub> alkyl, -deuterated C<com:Sub>1-3< / com:Sub> alkyl, -S-C<com:Sub>1-3< / com:Sub> alkyl, -S- halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'< / annotation>< / semantics>< / com:Math>-cyano, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>−C1−3<annotation encoding="application / x-tex">-C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(CRa1′Rb1′)u′<annotation encoding="application / x-tex">(CR_{a1}'R_{b1}')_{u}'< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'< / annotation>< / semantics>< / com:Math>-3- to 6-membered heterocycloalkyl, <com:Math><semantics>−(CRa1′Rb1′)u′−C3−6<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u'}-C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u'}< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u'}< / annotation>< / semantics>< / com:Math>-5- or 6- membered monocyclic heteroaryl, -(CR<com:Sub>a1< / com:Sub>'R<com:Sub>b1< / com:Sub>')<com:Sub>u< / com:Sub>'-O-(CR<com:Sub>a2< / com:Sub>'R<com:Sub>b2< / com:Sub>')<com:Sub>v< / com:Sub>'-halo C<com:Sub>1-3< / com:Sub> alkyl, -(CR<com:Sub>a1< / com:Sub>'R<com:Sub>b1< / com:Sub>')<com:Sub>u< / com:Sub>'-O- <com:Math><semantics>(CRa2′Rb2′)v′−C3−6<annotation encoding="application / x-tex">(CR_{a2}'R_{b2}')_{v}'-C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−(CRa1′Rb1′)u′−O−(CRa2′Rb2′)v′−3−<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-3-< / annotation>< / semantics>< / com:Math> to 6-membered heterocycloalkyl, <com:Math><semantics>−(CRa1′Rb1′)u′−O−(CRa2′Rb2′)v′−3−<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-3-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>(CRa1′Rb1′)u′−O−(CRa2′Rb2′)v−phenyl,<annotation encoding="application / x-tex">(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}-phenyl,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CRa1′Rb1′)u′−O−(CRa2′Rb2′)v′−5−<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-5-< / annotation>< / semantics>< / com:Math> or 6-membered monocyclic heteroaryl, <com:Math><semantics>−(CRa1′Rb1′)u<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_u< / annotation>< / semantics>< / com:Math>-S-<com:Math><semantics>(CRa2′Rb2′)v<annotation encoding="application / x-tex">(CR_{a2}'R_{b2}')_v< / annotation>< / semantics>< / com:Math>'-phenyl, <com:Math><semantics>−(CRa1′Rb1′)u<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_u< / annotation>< / semantics>< / com:Math>'-SO<com:Sub>2< / com:Sub>-<com:Math><semantics>(CRa2′Rb2′)v<annotation encoding="application / x-tex">(CR_{a2}'R_{b2}')_v< / annotation>< / semantics>< / com:Math>'- phenyl, <com:Math><semantics>−(CRa1′Rb1′)u′−O−C(O)NRa0′Rb0′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-O-C(O)NR_{a0}'R_{b0}'< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1′Rb1′)u′−O−(CRa2′Rb2′)v′−C1−3<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>(CRa1′Rb1′)u′−O−(CRa2′Rb2′)v′−hydroxyl,<annotation encoding="application / x-tex">(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-hydroxyl,< / annotation>< / semantics>< / com:Math> <com:Math><semantics>−(CRa1′Rb1′)u′−SO2C1−3<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'-SO_{2}C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1′Rb1′)u′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_{u}'< / annotation>< / semantics>< / com:Math> <com:Math><semantics>SO2NRa0′Rb0′<annotation encoding="application / x-tex">SO_2NR_{a0}'R_{b0}'< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1′Rb1′)u′−C(O)NRa0′Rb0′<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_u'-C(O)NR_{a0}'R_{b0}'< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1′Rb1′)u′−C(O)<annotation encoding="application / x-tex">-(CR_{a1}'R_{b1}')_u'-C(O)< / annotation>< / semantics>< / com:Math> alkyl, -C(O)OC<com:Sub>1-3< / com:Sub>alkyl, and-C(O)-(CR<com:Sub>a2< / com:Sub>'R<com:Sub>b2< / com:Sub>')<com:Sub>v< / com:Sub>'-hydroxyl, wherein the C<com:Sub>3-6< / com:Sub> cycloalkyl, 3- to 6- membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math>cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u' and v' are each independently 0, 1, 2, 3 or 4; <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> are each independently hydrogen or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; or <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl, wherein the 3- to 8- membered nitrogen-containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or C<com:Sub>1-3< / com:Sub> alkyl; R<com:Sub>a1< / com:Sub>', R<com:Sub>b1< / com:Sub>', R<com:Sub>a2< / com:Sub>' and R<com:Sub>b2< / com:Sub>' are the same or different, and are each independently hydrogen, hydroxyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl. 91 In an embodiment of the present disclosure, the substituents from group S' are selected from deuterium, halogen, nitro, oxo, -C<com:Sub>1-3< / com:Sub> alkyl, -halo C<com:Sub>1-3< / com:Sub> alkyl, -deuterated C<com:Sub>1-3< / com:Sub> alkyl, -S-C<com:Sub>1-3< / com:Sub> alkyl, -S- halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-cyano, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-halo C<com:Sub>1-3< / com:Sub> alkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-3- to 6-membered heterocycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-C<com:Sub>3-6< / com:Sub> cycloalkyl, - (CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-5- or 6-membered monocyclic heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-halo C<com:Sub>1-3< / com:Sub> alkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-C<com:Sub>3-6< / com:Sub> cycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-3- to 6-membered heterocycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-5- or 6-membered monocyclic heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>- S-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-SO<com:Sub>2< / com:Sub>-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-C(O)NR<com:Sub>a0< / com:Sub>'R<com:Sub>b0< / com:Sub>', -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>'-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>'- <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math>alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>O−(CH2)v<annotation encoding="application / x-tex">O-(CH_2)_v< / annotation>< / semantics>< / com:Math>'-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>SO2C1−3<annotation encoding="application / x-tex">SO_2C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>SO2NRa0<annotation encoding="application / x-tex">SO_2NR_{a0}< / annotation>< / semantics>< / com:Math>'<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', <com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>C(O)NRa0<annotation encoding="application / x-tex">C(O)NR_{a0}< / annotation>< / semantics>< / com:Math>'<com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math>', -<com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>phenyl, -<com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>'-<com:Math><semantics>C(O)C1−3<annotation encoding="application / x-tex">C(O)C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, -<com:Math><semantics>C(O)OC1−3<annotation encoding="application / x-tex">C(O)OC_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, and- <com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>'-hydroxyl, wherein the <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u' and v' are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub>' and R<com:Sub>b0< / com:Sub>' are each independently hydrogen or C<com:Sub>1-3< / com:Sub> alkyl; or R<com:Sub>a0< / com:Sub>' and R<com:Sub>b0< / com:Sub>' form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl, wherein the 3- to 8-membered nitrogen-containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or C<com:Sub>1-3< / com:Sub> alkyl; R<com:Sub>a1< / com:Sub>', R<com:Sub>b1< / com:Sub>', R<com:Sub>a2< / com:Sub>' and <com:Math><semantics>Rb2<annotation encoding="application / x-tex">R_{b2}< / annotation>< / semantics>< / com:Math> are the same or different, and are each independently hydrogen, hydroxyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> 3 alkyl.

[92] In an embodiment of the present disclosure, in the substituents from group S and group S', the 3- to 6-membered heterocycloalkyl is selected from aziridine, ethylene oxide, azetidine, azetidine- 2-one, oxetane, oxetane-2-one, oxazolidine, pyrrolidine-2-one, pyrrolidine-2,5-dione, 1,3- dioxolane, dihydrofuran-2(3H)-one, dihydrofuran-2,5-dione, piperidine-2-one, piperidine-2,6- dione, tetrahydro-2H-pyran-2-one, imidazolidine, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, 1,3-dioxolane-2-one, oxazolidine-2-one, imidazolidine-2-one, piperidine, piperazine, piperazine-2-one, morpholine, morpholine-3-one, morpholine-2-one, thiomorpholine-3- one 1,1-dioxide, thiomorpholine, thiomorpholine-1,1-dioxide, tetrahydropyran, 1,2- dihydroazetidine, 1,2-dihydrooxetadiene, 2,5-dihydro-1H-pyrrole, 2,5-dihydrofuran, 2,3- dihydrofuran, 2,3-dihydro-1H-pyrrole, 3,4-dihydro-2H-pyran, 1,2,3,4-tetrahydropyridine, 3,6- dihydro-2H-pyran, 1,2,3,6-tetrahydropyridine, 1,3-oxazinane, hexahydropyrimidine, 1,4-dioxane, tetrahydropyrimidine-2(1H)-one, 1,4-dioxane-2-one, and 5,6-dihydro-2H-pyran-2-one. 93 In an embodiment of the present disclosure, in the substituents from group S and group S', the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-1,3-dione.

[94] In an embodiment of the present disclosure, in the substituents from group S and group S', the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, N-alkylpyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine.

[95] In an embodiment of the present disclosure, the compound has a structure represented by formula (I-1): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−1)<annotation encoding="application / x-tex">(I-1)< / annotation>< / semantics>< / com:Math>

[96] wherein, A, <com:Math><semantics>R1<annotation encoding="application / x-tex">R_1< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R2<annotation encoding="application / x-tex">R_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R3<annotation encoding="application / x-tex">R_3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R4<annotation encoding="application / x-tex">R_4< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R5<annotation encoding="application / x-tex">R_5< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R6<annotation encoding="application / x-tex">R_6< / annotation>< / semantics>< / com:Math> are as defined above; i and j are each independently 0, 1 or 2; and i and j are not 0 at the same time;

[97] <com:Math><semantics>R7<annotation encoding="application / x-tex">R_7< / annotation>< / semantics>< / com:Math> is hydrogen, deuterium, halogen, nitro, oxo, <com:Math><semantics>−C1−6<annotation encoding="application / x-tex">-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -deuterated <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -S-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -S-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-cyano, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-hydroxyl, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-deuterated <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-deuterated C<com:Sub>1-6< / com:Sub> alkyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-3- to 6-membered heterocycloalkyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-C<com:Sub>3-8< / com:Sub> cycloalkyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-phenyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-5- or 6-membered monocyclic heteroaryl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>- <com:Math><semantics>O−(CRa2Rb2)v<annotation encoding="application / x-tex">O-(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alky l, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>O−(CRa2Rb2)v<annotation encoding="application / x-tex">O-(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalky l, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>O−(CRa2Rb2)v<annotation encoding="application / x-tex">O-(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>- 3- to 6-membered heterocycloalkyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CR<com:Sub>a2< / com:Sub>R<com:Sub>b2< / com:Sub>)<com:Sub>v< / com:Sub>-phenyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CR<com:Sub>a2< / com:Sub>R<com:Sub>b2< / com:Sub>)<com:Sub>v< / com:Sub>- 5- or 6-membered monocyclic heteroaryl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-S-(CR<com:Sub>a2< / com:Sub>R<com:Sub>b2< / com:Sub>)<com:Sub>v< / com:Sub>-phenyl, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-SO<com:Sub>2< / com:Sub>- <com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_{v}< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>C(O)NRa0Rb0<annotation encoding="application / x-tex">C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_{v}< / annotation>< / semantics>< / com:Math>-C<com:Sub>1-6< / com:Sub> alkoxy, - <com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_{u}< / annotation>< / semantics>< / com:Math>-O-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_{v}< / annotation>< / semantics>< / com:Math>-hydroxyl, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_{u}< / annotation>< / semantics>< / com:Math>-SO<com:Sub>2< / com:Sub>C<com:Sub>1-6< / com:Sub> alkyl, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_{u}< / annotation>< / semantics>< / com:Math>-SO<com:Sub>2< / com:Sub>NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, - <com:Math><semantics>(CRa1Rb1)u−C(O)NRa0Rb0<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_{u}-C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u−C(O)<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-C(O)< / annotation>< / semantics>< / com:Math> phenyl, <com:Math><semantics>−(CRa1Rb1)u−C(O)C1−6<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)OC1−6<annotation encoding="application / x-tex">-C(O)OC_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)OC1−6<annotation encoding="application / x-tex">-C(O)OC_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)OC1−6<annotation encoding="application / x-tex">-C(O)OC_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)OC1−6<annotation encoding="application / x-tex">-C(O)OC_{1-6}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)−(CRa2Rb2)v−hydroxyl,−(CRa1Rb1)u−NRa0Rb0,−NRa0C(O)−C1−6<annotation encoding="application / x-tex">C(O)-(CR_{a2}R_{b2})_v-hydroxyl, -(CR_{a1}R_{b1})_u-NR_{a0}R_{b0}, -NR_{a0}C(O)-C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-deuterated <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−NRa0C(O)−(CRa1Rb1)u−hydroxyl<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CR_{a1}R_{b1})_u-hydroxyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRa0C(O)−(CRa1Rb1)u−O−(CRa2Rb2)v−C(O)C1−6<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CR_{a1}R_{b1})_u-O-(CR_{a2}R_{b2})_v-C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−<annotation encoding="application / x-tex">-< / annotation>< / semantics>< / com:Math> <com:Math><semantics>NRa0C(O)−(CRa1Rb1)u−O−(CRa2Rb2)v−phenyl<annotation encoding="application / x-tex">NR_{a0}C(O)-(CR_{a1}R_{b1})_{u}-O-(CR_{a2}R_{b2})_{v}-phenyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRa0C(O)−C3−8<annotation encoding="application / x-tex">-NR_{a0}C(O)-C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−NRa0C(O)−(CRa1Rb1)u−Phenyl<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CR_{a1}R_{b1})_{u}-Phenyl< / annotation>< / semantics>< / com:Math> <com:Math><semantics>NRa0Rb0<annotation encoding="application / x-tex">NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, wherein the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo C<com:Sub>3-6< / com:Sub> cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> are each independently hydrogen or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; or <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl, wherein the 3- to 8-membered nitrogen-containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or C<com:Sub>1-3< / com:Sub> alkyl; R<com:Sub>a1< / com:Sub>, R<com:Sub>b1< / com:Sub>, R<com:Sub>a2< / com:Sub> and R<com:Sub>b2< / com:Sub> are the same or different, and are each independently hydrogen, hydroxyl, C<com:Sub>1< / com:Sub>. 3 alkyl or halo C<com:Sub>1-3< / com:Sub> alkyl; <com:Math><semantics>98R8<annotation encoding="application / x-tex">98R_8< / annotation>< / semantics>< / com:Math> is hydrogen, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>SO2<annotation encoding="application / x-tex">SO_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-phenyl, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>SO2C1−6<annotation encoding="application / x-tex">SO_2C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -<com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>- <com:Math><semantics>SO2NRa0Rb0<annotation encoding="application / x-tex">SO_2NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)NRa0Rb0<annotation encoding="application / x-tex">C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>phenyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)C1−6<annotation encoding="application / x-tex">C(O)C_{1-6}< / annotation>< / semantics>< / com:Math>alkyl, or- <com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-hydroxyl, wherein the phenyl and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl are optionally substituted with 1, 2, 3 or 4 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo C<com:Sub>3-6< / com:Sub> cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> are each independently hydrogen or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; or <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl; R<com:Sub>a1< / com:Sub>, R<com:Sub>b1< / com:Sub>, R<com:Sub>a2< / com:Sub> and R<com:Sub>b2< / com:Sub> are the same or different, and are each independently hydrogen, hydroxyl, C<com:Sub>1-3< / com:Sub> alkyl or halo C<com:Sub>1-3< / com:Sub> alkyl;

[99] the rest of the groups are as defined above. <com:Math><semantics>⌈100⌉<annotation encoding="application / x-tex">\lceil 100 \rceil< / annotation>< / semantics>< / com:Math> In an embodiment of the present disclosure, the compound of formula (I-1) has a structure represented by formula (I-1-a), formula (I-1-b), formula (I-1-c) or formula (I-1-d): [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] I-1-a I-1-b [Image disponible dans le document PDF, Image available in the PDF document] • [Image disponible dans le document PDF, Image available in the PDF document] > I-1-c 7

[101] in each formula, each group is as defined above. <com:Math><semantics>⌈102⌉<annotation encoding="application / x-tex">\lceil 102 \rceil< / annotation>< / semantics>< / com:Math> In an embodiment of the present disclosure, the compound has a structure represented by formula (I-2): [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>(I−2)<annotation encoding="application / x-tex">(I-2)< / annotation>< / semantics>< / com:Math>

[103] wherein, A, R<com:Sub>7< / com:Sub> and R<com:Sub>8< / com:Sub> are as defined above. <com:Math><semantics>⌈104⌉<annotation encoding="application / x-tex">\lceil 104 \rceil< / annotation>< / semantics>< / com:Math> In an embodiment of the present disclosure, the compound of formula (I-2) has a structure represented by formula (I-2-a), formula (I-2-b), formula (I-2-c) or formula (I-2-d): [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] 2 [Image disponible dans le document PDF, Image available in the PDF document] , •

[105] in each formula, each group is as defined above.

[106] In an embodiment of the present disclosure, R<com:Sub>7< / com:Sub> is hydrogen, deuterium, halogen, nitro, - <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, -halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, -deuterated <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, -S-C<com:Sub>1-3< / com:Sub> alkyl, -S-halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-cyano, - <com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>- deuterated <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-deuterated <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-3- to 6-membered heterocycloalkyl, - (CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-C<com:Sub>3-8< / com:Sub> cycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-5- or 6-membered monocyclic heteroaryl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>- <com:Math><semantics>O−(CH2)v<annotation encoding="application / x-tex">O-(CH_2)_v< / annotation>< / semantics>< / com:Math>-halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>O−(CH2)v<annotation encoding="application / x-tex">O-(CH_2)_v< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>O−(CH2)v<annotation encoding="application / x-tex">O-(CH_2)_v< / annotation>< / semantics>< / com:Math>-3- to 6-membered heterocycloalkyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-phenyl, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-O-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-5- or 6-membered monocyclic heteroaryl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-S-<com:Math><semantics>−(CH2)v<annotation encoding="application / x-tex">-(CH_2)_v< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-SO<com:Sub>2< / com:Sub>-<com:Math><semantics>−(CH2)v<annotation encoding="application / x-tex">-(CH_2)_v< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-C(O)NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, <com:Math><semantics>−(CH2)v<annotation encoding="application / x-tex">-(CH_2)_v< / annotation>< / semantics>< / com:Math>-phenyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-O-C(O)NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, <com:Math><semantics>−(CH2)v<annotation encoding="application / x-tex">-(CH_2)_v< / annotation>< / semantics>< / com:Math>-phenyl <com:Math><semantics>(CH2)u−O−(CH2)v−C1−6<annotation encoding="application / x-tex">(CH_2)_{u}-O-(CH_2)_{v}-C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>−(CH2)u−O−(CH2)v−hydroxyl<annotation encoding="application / x-tex">-(CH_2)_{u}-O-(CH_2)_{v}-hydroxyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)u−SO2C1−6<annotation encoding="application / x-tex">-(CH_2)_{u}-SO_2C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CH2)u−C1CH2<annotation encoding="application / x-tex">-(CH_2)_{u}-C_1CH_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>SO2NRa0Rb0<annotation encoding="application / x-tex">SO_2NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)u−C(O)NRa0Rb0<annotation encoding="application / x-tex">-(CH_2)_u-C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)u−C(O)<annotation encoding="application / x-tex">-(CH_2)_u-C(O)< / annotation>< / semantics>< / com:Math> phenyl, <com:Math><semantics>−(CH2)u−C(O)C1−6<annotation encoding="application / x-tex">-(CH_2)_u-C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)OC1−6<annotation encoding="application / x-tex">-C(O)OC_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C(O)−(CH2)v<annotation encoding="application / x-tex">-C(O)-(CH_2)_v< / annotation>< / semantics>< / com:Math>-hydroxyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>−NRa0C(O)<annotation encoding="application / x-tex">-NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>-deuterated C<com:Sub>1-6< / com:Sub> alkyl, <com:Math><semantics>−NRa0C(O)−(CH2)u−hydroxyl<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CH_2)_u-hydroxyl< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRa0C(O)−C3−8<annotation encoding="application / x-tex">-NR_{a0}C(O)-C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl, <com:Math><semantics>−NRa0C(O)−(CH2)u−NRa0Rb0<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CH_2)_u-NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRa0C(O)−(CH2)u−NRa0Rb0<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CH_2)_u-NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−NRa0C(O)−(CH2)u−NRa0Rb0<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CH_2)_u-NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>NRa0C(O)−(CH2)u−O−(CH2)v−C(O)C1−6<annotation encoding="application / x-tex">NR_{a0}C(O)-(CH_2)_u-O-(CH_2)_v-C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−NRa0C(O)−(CH2)u−O−(CH2)v<annotation encoding="application / x-tex">-NR_{a0}C(O)-(CH_2)_u-O-(CH_2)_v< / annotation>< / semantics>< / com:Math>-phenyl, or-<com:Math><semantics>NRa0C(O)<annotation encoding="application / x-tex">NR_{a0}C(O)< / annotation>< / semantics>< / com:Math>- halo C<com:Sub>1-6< / com:Sub> alkyl, wherein the C<com:Sub>3-8< / com:Sub> cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, C<com:Sub>1-3< / com:Sub> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> are each independently hydrogen or C<com:Sub>1-3< / com:Sub> alkyl; or R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen- containing heterocycloalkyl, wherein the 3- to 8-membered nitrogen-containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl.

[107] In an embodiment of the present disclosure, R<com:Sub>7< / com:Sub> is hydrogen, deuterium, halogen, nitro, - <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, -halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, or-deuterated <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl.

[108] In an embodiment of the present disclosure, R<com:Sub>8< / com:Sub> is hydrogen, -(CR<com:Sub>a1< / com:Sub>R<com:Sub>b1< / com:Sub>)<com:Sub>u< / com:Sub>-SO<com:Sub>2< / com:Sub>-(CR<com:Sub>a2< / com:Sub>R<com:Sub>b2< / com:Sub>)<com:Sub>v< / com:Sub>- phenyl, <com:Math><semantics>−(CRa1Rb1)u−SO2C1−3<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-SO_{2}C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−(CRa1Rb1)u−SO2NRa0Rb0<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-SO_{2}NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u−C(O)NRa0Rb0<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u−C(O)NRa0Rb0<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CRa1Rb1)u−C(O)NRa0Rb0<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_{u}-C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <Formule mathématique disponible dans le document PDF, Math available in the PDF document>-(CR_{ <com:Math><semantics>(CRa1Rb1)u<annotation encoding="application / x-tex">(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>phenyl, <com:Math><semantics>−(CRa1Rb1)u<annotation encoding="application / x-tex">-(CR_{a1}R_{b1})_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)C1−3<annotation encoding="application / x-tex">C(O)C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, or-<com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CRa2Rb2)v<annotation encoding="application / x-tex">(CR_{a2}R_{b2})_v< / annotation>< / semantics>< / com:Math>-hydroxyl, wherein the phenyl and <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl are optionally substituted with 1, 2, 3 or 4 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> are each independently hydrogen or C<com:Sub>1-3< / com:Sub> alkyl; or R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl; R<com:Sub>a1< / com:Sub>, R<com:Sub>b1< / com:Sub>, R<com:Sub>a2< / com:Sub> and R<com:Sub>b2< / com:Sub> are the same or different, and are each independently hydrogen, hydroxyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl. <com:Math><semantics>⌈109⌉<annotation encoding="application / x-tex">\lceil 109 \rceil< / annotation>< / semantics>< / com:Math> In an embodiment of the present disclosure, R<com:Sub>8< / com:Sub> is hydrogen, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-SO<com:Sub>2< / com:Sub>-(CH<com:Sub>2< / com:Sub>)<com:Sub>v< / com:Sub>-phenyl, <com:Math><semantics>−(CH2)u−SO2C1−6<annotation encoding="application / x-tex">-(CH_2)_u-SO_2C_{1-6}< / annotation>< / semantics>< / com:Math> alky l, <com:Math><semantics>−(CH2)u−SO2NRa0Rb0<annotation encoding="application / x-tex">-(CH_2)_u-SO_2NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)u−C(O)NRa0Rb0<annotation encoding="application / x-tex">-(CH_2)_u-C(O)NR_{a0}R_{b0}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>−(CH2)u−C(O)<annotation encoding="application / x-tex">-(CH_2)_u-C(O)< / annotation>< / semantics>< / com:Math> pheny l, <com:Math><semantics>−(CH2)u−C(O)<annotation encoding="application / x-tex">-(CH_2)_u-C(O)< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C(O)C1−6<annotation encoding="application / x-tex">C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, or-<com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-hydroxyl, wherein the phenyl and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl are optionally substituted with 1, 2, 3 or 4 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> are each independently hydrogen or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl; or <com:Math><semantics>Ra0<annotation encoding="application / x-tex">R_{a0}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>Rb0<annotation encoding="application / x-tex">R_{b0}< / annotation>< / semantics>< / com:Math> form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl.

[110] In an embodiment of the present disclosure, R<com:Sub>8< / com:Sub> is hydrogen, -(CH<com:Sub>2< / com:Sub>)<com:Sub>u< / com:Sub>-C(O)NR<com:Sub>a0< / com:Sub>R<com:Sub>b0< / com:Sub>, - <com:Math><semantics>(CH2)u<annotation encoding="application / x-tex">(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>phenyl, <com:Math><semantics>−(CH2)u<annotation encoding="application / x-tex">-(CH_2)_u< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C(O)C1−3<annotation encoding="application / x-tex">C(O)C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, or-<com:Math><semantics>C(O)<annotation encoding="application / x-tex">C(O)< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(CH2)v<annotation encoding="application / x-tex">(CH_2)_v< / annotation>< / semantics>< / com:Math>-hydroxyl, wherein the phenyl and <com:Math><semantics>C1−1<annotation encoding="application / x-tex">C_{1-1}< / annotation>< / semantics>< / com:Math> 3 alkyl are optionally substituted with 1, 2, 3 or 4 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl and halo <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> are each independently hydrogen or C<com:Sub>1-3< / com:Sub> alkyl; or R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl.

[111] In an embodiment of the present disclosure, R<com:Sub>8< / com:Sub> is hydrogen, -C(O)phenyl, or-C(O)C<com:Sub>1< / com:Sub>. <com:Sub>6< / com:Sub>alkyl, wherein the phenyl, and <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl are optionally substituted with 1, 2, 3 or 4 substituents selected from hydroxyl, halogen, and halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl.

[112] In an embodiment of the present disclosure, R<com:Sub>8< / com:Sub> is hydrogen, -C(O)phenyl, or-C(O)C<com:Sub>1-3< / com:Sub> alkyl, wherein the <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl is methyl, ethyl, n-propyl or isopropyl; the phenyl, and <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl are optionally substituted with 1, 2, 3 or 4 substituents selected from hydroxyl, fluorine, chlorine, monochloromethyl, dichloromethyl, trichloromethyl, monochloroethyl, 1,2-dichloroethyl, trichloroethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, and trifluoroethyl. <com:Math><semantics>⌈113⌉<annotation encoding="application / x-tex">\lceil 113 \rceil< / annotation>< / semantics>< / com:Math> In an embodiment of the present disclosure, R<com:Sub>8< / com:Sub> has a structure represented by formula (I- 1-1): [Image disponible dans le document PDF, Image available in the PDF document] I-1-1

[114] wherein R<com:Sub>81< / com:Sub>, R<com:Sub>82< / com:Sub> and R<com:Sub>83< / com:Sub> are each independently hydrogen, hydroxyl, halogen, C<com:Sub>1-3< / com:Sub> alkyl, halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy. |115| In an embodiment of the present disclosure, R<com:Sub>8< / com:Sub> has a structure as follows: [Image disponible dans le document PDF, Image available in the PDF document]

[116] In an embodiment of the present disclosure, A has a structure selected from: [Image disponible dans le document PDF, Image available in the PDF document] •

[117] wherein R<com:Sub>Y01< / com:Sub>, R<com:Sub>Y02< / com:Sub>, R<com:Sub>U8< / com:Sub>, R<com:Sub>U1< / com:Sub> and R<com:Sub>G0< / com:Sub> are each independently hydrogen or the substituents from group S.

[118] In an embodiment of the present disclosure, A is substituted or unsubstituted pyridine, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzopyridine, substituted or unsubstituted pyrrolotriazine, substituted or unsubstituted tetrahydro-triazolopyrazine, substituted or unsubstituted imidazopyridazine, or substituted or unsubstituted triazolopyridine, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S.

[119] In an embodiment of the present disclosure, A is or substituted or unsubstituted benzothiazole, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S'.

[120] In an embodiment of the present disclosure, A is substituted or unsubstituted pyridine, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted pyrrolotriazine, substituted or unsubstituted 5,6,7,8-tetrahydro-triazolopyrazine, substituted or unsubstituted imidazopyridazine, or substituted or unsubstituted [1,2,4]triazolo[1,5- a]pyridine; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S.

[121] In an embodiment of the present disclosure, A is substituted or unsubstituted pyridine, substituted or unsubstituted 1H-benzimidazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted [2,1-f]pyrrolo[1,2,4]triazine, substituted or unsubstituted 5,6,7,8- tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine, or substituted or unsubstituted imidazo[1,2-b]pyridazine, or substituted or unsubstituted [1,2,4]triazolo[1,5-a]pyridine; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S.

[122] In an embodiment of the present disclosure, A is selected from: [Image disponible dans le document PDF, Image available in the PDF document] independently unsubstituted or substituted; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S.

[123] In an embodiment of the present disclosure, A has a structure selected from: [Image disponible dans le document PDF, Image available in the PDF document]

[124] wherein R<com:Sub>E1< / com:Sub>, R<com:Sub>W01< / com:Sub>, R<com:Sub>W02< / com:Sub>, R<com:Sub>W02< / com:Sub>, R<com:Sub>W03< / com:Sub>, R<com:Sub>Y01< / com:Sub>, R<com:Sub>Y02< / com:Sub>, R<com:Sub>U8< / com:Sub>, R<com:Sub>U1< / com:Sub> and R<com:Sub>G0< / com:Sub> are each independently hydrogen or the substituent from group S; R<com:Sub>E0< / com:Sub> is hydrogen or the substituent from group S'; m is 1, 2, 3 or 4.

[125] In an embodiment of the present disclosure, A is selected from: [Image disponible dans le document PDF, Image available in the PDF document]

[126] In an embodiment of the present disclosure, A is substituted or unsubstituted benzothiazole; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S'.

[127] In an embodiment of the present disclosure, A is substituted or unsubstituted [Image disponible dans le document PDF, Image available in the PDF document] ; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S'. [Image disponible dans le document PDF, Image available in the PDF document]

[128] In an embodiment of the present disclosure, A is

[129] In an embodiment of the present disclosure, R<com:Sub>1< / com:Sub> and R<com:Sub>2< / com:Sub> are each independently hydrogen, halogen, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl.

[130] In an embodiment of the present disclosure, R<com:Sub>3< / com:Sub>, R<com:Sub>4< / com:Sub>, R<com:Sub>5< / com:Sub> and R<com:Sub>6< / com:Sub> are each independently hydrogen, <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl or halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl.

[131] In an embodiment of the present disclosure,

[132] with regard to <com:Math><semantics>R0<annotation encoding="application / x-tex">R_0< / annotation>< / semantics>< / com:Math>, the <com:Math><semantics>C6−14<annotation encoding="application / x-tex">C_{6-14}< / annotation>< / semantics>< / com:Math> aryl is phenyl, naphthyl, or is a 9- or 10-membered aromatic fused bicyclic ring formed by fusing phenyl with a non-aromatic ring; the non-aromatic ring is 3- to 6-membered saturated or partially unsaturated monocyclic heterocycloalkyl or 3- to 6-membered saturated or partially unsaturated monocyclic cycloalkyl, wherein the 3- to 6-membered saturated or partially unsaturated monocyclic heterocycloalkyl is selected from aziridine, ethylene oxide, azetidine, azetidine-2-one, oxetane, oxetane-2-one, oxazolidine, pyrrolidine-2-one, pyrrolidine-2,5- dione, 1,3-dioxolane, dihydrofuran-2(3H)-one, dihydrofuran-2,5-dione, piperidine-2-one, piperidine-2,6-dione, tetrahydro-2H-pyran-2-one, imidazolidine, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, 1,3-dioxolane-2-one, oxazolidine-2-one, imidazolidine-2- one, piperidine, piperazine, piperazine-2-one, morpholine, morpholine-3-one, morpholine-2-one, thiomorpholine-3-one 1,1-dioxide, thiomorpholine, thiomorpholine-1,1-dioxide, tetrahydropyran, 1,2-dihydroazetidine, 1,2-dihydrooxetadiene, 2,5-dihydro-1H-pyrrole, 2,5-dihydrofuran, 2,3- dihydrofuran, 2,3-dihydro-1H-pyrrole, 3,4-dihydro-2H-pyran, 1,2,3,4-tetrahydropyridine, 3,6- dihydro-2H-pyran, 1,2,3,6-tetrahydropyridine, 1,3-oxazinane, hexahydropyrimidine, 1,4-dioxane, tetrahydropyrimidine-2(1H)-one, 1,4-dioxane-2-one, and 5,6-dihydro-2H-pyran-2-one; the 3- to 6- membered saturated or partially unsaturated monocyclic cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane- 1,3-dione; the phenyl, naphthyl, or 9- or 10-membered aromatic fused bicyclic ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[133] In an embodiment of the present disclosure, with regard to <com:Math><semantics>R0<annotation encoding="application / x-tex">R_0< / annotation>< / semantics>< / com:Math>, the <com:Math><semantics>C6−14<annotation encoding="application / x-tex">C_{6-14}< / annotation>< / semantics>< / com:Math> aryl is phenyl.

[134] In an embodiment of the present disclosure, with regard to R<com:Sub>0< / com:Sub>, the 5- to 14-membered heteroaryl is 5- or 6-membered monocyclic heteroaryl, wherein the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, N-alkylpyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4- oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine; the 5- or 6-membered monocyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[135] In an embodiment of the present disclosure, with regard to <com:Math><semantics>R0<annotation encoding="application / x-tex">R_0< / annotation>< / semantics>< / com:Math>, when the 5- to 14- membered heteroaryl is 5- or 6-membered monocyclic heteroaryl, the monocyclic heteroaryl is selected from the following structures: NH, NH, O, S, S, NH, NH, NH, NH, NH, NH, NH, NH, NH, NH [Image disponible dans le document PDF, Image available in the PDF document] heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[136] In an embodiment of the present disclosure, with regard to R<com:Sub>0< / com:Sub>, the 5- to 14-membered heteroaryl is 9- or 10-membered bicyclic heteroaryl formed by fusing phenyl with 5- or 6-membered monocyclic heteroaryl, wherein the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, N-alkyl pyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine; the 9- or 10-membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[137] In an embodiment of the present disclosure, the 9- or 10-membered bicyclic heteroaryl formed by fusing phenyl with 5- or 6-membered monocyclic heteroaryl has a structure represented by formula (A1) or formula (B1): [Image disponible dans le document PDF, Image available in the PDF document]

[138] wherein ring C is 5- or 6-membered monocyclic heteroaryl, wherein the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, N-alkyl pyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4- triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine; the 9- or 10-membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[139] In an embodiment of the present disclosure, ring C is selected from the following structure: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] بسه 15 are adjacent pairs of carbon atoms shared when fused with phenyl.

[140] In an embodiment of the present disclosure, the 9- or 10-membered bicyclic heteroaryl formed by fusing phenyl with 5- or 6-membered monocyclic heteroaryl is selected from benzoxazole, benzisoxazole, benzimidazole, benzothiazole, benzisothiazole, benzisothiazole, benzofuran, benzothiophene, indole, indazole, isoindole, quinoline, isoquinoline, quinazoline, quinoxaline, and cinnoline; the 9- or 10-membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[141] In an embodiment of the present disclosure, the 9- or 10-membered bicyclic heteroaryl formed by fusing phenyl with 5- or 6-membered monocyclic heteroaryl is selected from benzo[d]isoxazole, 1H-indole, isoindole, 1H-benzo[d]imidazole, benzo[d]isothiazole, 1H- benzo[d][1,2,3]triazole, benzo[d]oxazole, benzo[d]thiazole, indazole, benzofuran, benzo[b]thiophene, quinoline, isoquinoline, quinazoline, quinoxaline, and cinnoline; the 9- or 10- membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[142] In an embodiment of the present disclosure, the 9- or 10-membered bicyclic heteroaryl formed by fusing phenyl with 5- or 6-membered monocyclic heteroaryl is selected from the following structures: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] ; the above 9- or 10-membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[143] In an embodiment of the present disclosure, with regard to R<com:Sub>0< / com:Sub>, the 5- to 14-membered heteroaryl is 8- to 10-membered bicyclic heteroaryl formed by fusing 5- or 6-membered monocyclic heteroaryl with 5- or 6-membered monocyclic heteroaryl, wherein the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, N-alkylpyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4- triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine; the 8- to 10-membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[144] In an embodiment of the present disclosure, the 8- to 10-membered bicyclic heteroaryl formed by fusing 5- or 6-membered monocyclic heteroaryl with 5- or 6-membered monocyclic heteroaryl has a structure represented by formula (C) or formula (D): D E C D

[145] wherein ring D and ring E are 5- or 6-membered monocyclic heteroaryl, wherein the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, N-alkyl pyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine; the 8- to 10-membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[146] In an embodiment of the present disclosure, ring D and ring E are selected from the following structures: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] , wherein the attached two carbon atoms represented by " ~~ " are adjacent pairs of carbon atoms shared when fused with other rings.

[147] In an embodiment of the present disclosure, the 8- to 10-membered bicyclic heteroaryl formed by fusing 5- or 6-membered monocyclic heteroaryl with 5- or 6-membered monocyclic heteroaryl is selected from pyridopyrimidine and naphthyridine.

[148] In an embodiment of the present disclosure, the 8- to 10-membered bicyclic heteroaryl formed by fusing 5- or 6-membered monocyclic heteroaryl with 5- or 6-membered monocyclic heteroaryl is selected from pyrido[3,2-d]pyrimidine, pyrido[2,3-d]pyrimidine, pyrido[3,4- d]pyrimidine, pyrido[4,3-d]pyrimidine, 1,8-naphthyridine, 1,7-naphthyridine, 1,6-naphthyridine, and 1,5-naphthyridine.

[149] In an embodiment of the present disclosure, the 8- to 10-bicyclic heteroaryl formed by fusing 5- or 6-membered monocyclic heteroaryl with 5- or 6-membered monocyclic heteroaryl is [Image disponible dans le document PDF, Image available in the PDF document] selected from the following structures: 2 [Image disponible dans le document PDF, Image available in the PDF document] ; the above 8- to 10-membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[150] In an embodiment of the present disclosure, with regard to R<com:Sub>0< / com:Sub>, the 5- to 14-membered heteroaryl is 8- to 10-membered bicyclic heteroaryl formed by fusing 5- or 6-membered monocyclic heteroaryl with a non-aromatic ring, wherein the non-aromatic ring is 3- to 6-membered saturated or partially unsaturated monocyclic heterocycloalkyl or 3- to 6-membered saturated or partially unsaturated monocyclic cycloalkyl; the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, N-alkylpyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine; the 3- to 6-membered saturated or partially unsaturated monocyclic heterocycloalkyl is selected from aziridine, ethylene oxide, azetidine, azetidine-2-one, oxetane, oxetane-2-one, oxazolidine, pyrrolidine-2-one, pyrrolidine-2,5-dione, 1,3-dioxolane, dihydrofuran-2(3H)-one, dihydrofuran-2,5-dione, piperidine-2-one, piperidine-2,6-dione, tetrahydro-2H-pyran-2-one, imidazolidine, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, 1,3-dioxolane-2-one, oxazolidine-2-one, imidazolidine-2-one, piperidine, piperazine, piperazine-2- one, morpholine, morpholine-3-one, morpholine-2-one, thiomorpholine-3-one 1,1-dioxide, thiomorpholine, thiomorpholine-1,1-dioxide, tetrahydropyran, 1,2-dihydroazetidine, 1,2- dihydrooxetadiene, 2,5-dihydro-1H-pyrrole, 2,5-dihydrofuran, 2,3-dihydrofuran, 2,3-dihydro-1H- pyrrole, 3,4-dihydro-2H-pyran, 1,2,3,4-tetrahydropyridine, 3,6-dihydro-2H-pyran, 1,2,3,6- tetrahydropyridine, 1,3-oxazinane, hexahydropyrimidine, 1,4-dioxane, tetrahydropyrimidine- 2(1H)-one, 1,4-dioxane-2-one, and 5,6-dihydro-2H-pyran-2-one; the 3- to 6-membered saturated or partially unsaturated monocyclic cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-1,3-dione; the 8- to 10- membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S. 151 In an embodiment of the present disclosure, with regard to R<com:Sub>0< / com:Sub>, the 5- to 14-membered heterocycloalkyl is 5- to 6-membered heterocycloalkyl, wherein the 5- to 6-membered heterocycloalkyl is selected from oxazolidine, pyrrolidine-2-one, pyrrolidine-2,5-dione, 1,3- dioxolane, dihydrofuran-2(3H)-one, dihydrofuran-2,5-dione, piperidine-2-one, piperidine-2,6- dione, tetrahydro-2H-pyran-2-one, imidazolidine, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, 1,3-dioxolane-2-one, oxazolidine-2-one, imidazolidine-2-one, piperidine, piperazine, piperazine-2-one, morpholine, morpholine-3-one, morpholine-2-one, thiomorpholine-3- one 1,1-dioxide, thiomorpholine, thiomorpholine-1,1-dioxide, tetrahydropyran, 1,2- dihydroazetidine, 1,2-dihydrooxetadiene, 2,5-dihydro-1H-pyrrole, 2,5-dihydrofuran, 2,3- dihydrofuran, 2,3-dihydro-1H-pyrrole, 3,4-dihydro-2H-pyran, 1,2,3,4-tetrahydropyridine, 3,6- dihydro-2H-pyran, 1,2,3,6-tetrahydropyridine, 1,3-oxazinane, hexahydropyrimidine, 1,4-dioxane, tetrahydropyrimidine-2(1H)-one, 1,4-dioxane-2-one, and 5,6-dihydro-2H-pyran-2-one; the 5- to 6- membered heterocycloalkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[152] In an embodiment of the present disclosure, with regard to R<com:Sub>0< / com:Sub>, the 5- to 14-membered heterocycloalkyl is 5- to 6-membered heterocycloalkyl, wherein the 5- to 6-membered heterocycloalkyl is selected from tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine, thiomorpholine-1,1-dioxide and tetrahydropyran; the 5- to 6-membered heterocycloalkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[153] In an embodiment of the present disclosure, R<com:Sub>0< / com:Sub> is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazolyl or substituted or unsubstituted tetrahydropyrrolyl; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S.

[154] In an embodiment of the present disclosure, <com:Math><semantics>R0<annotation encoding="application / x-tex">R_0< / annotation>< / semantics>< / com:Math> is selected from the following structures: [Image disponible dans le document PDF, Image available in the PDF document] <com:S>...< / com:S> [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] **** [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] >

[155] In an embodiment of the present disclosure, in the 9- or 10-membered aromatic fused bicyclic ring and 8- to 10-membered bicyclic heteroaryl, when the non-aromatic ring is 3- to 6- membered saturated or partially unsaturated monocyclic heterocycloalkyl, the monocyclic heterocycloalkyl is selected from the following structures: [Image disponible dans le document PDF, Image available in the PDF document]

[156] In an embodiment of the present disclosure, L is a bond.

[157] In an embodiment of the present disclosure, L is selected from the following structures: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]

[158] In an embodiment of the present disclosure, R<com:Sub>3< / com:Sub> and R<com:Sub>4< / com:Sub> form together with the carbon atom adjacent thereto a C<com:Sub>3-8< / com:Sub> cycloalkyl ring, which is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-<com:Math><semantics>1,3<annotation encoding="application / x-tex">1,3< / annotation>< / semantics>< / com:Math>-dione; the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[159] In an embodiment of the present disclosure, R<com:Sub>5< / com:Sub> and R<com:Sub>6< / com:Sub> form together with the carbon atom adjacent thereto a C<com:Sub>3-8< / com:Sub> cycloalkyl ring, which is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-1,3-dione; the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[160] In an embodiment of the present disclosure, R<com:Sub>4< / com:Sub> and R<com:Sub>5< / com:Sub> form together with the carbon atom adjacent thereto a C<com:Sub>3-8< / com:Sub> cycloalkyl ring, which is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-1,3-dione; the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[161] In an embodiment of the present disclosure, <com:Math><semantics>R21<annotation encoding="application / x-tex">R_{21}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R22<annotation encoding="application / x-tex">R_{22}< / annotation>< / semantics>< / com:Math> form together with the carbon atom adjacent thereto a C<com:Sub>3-8< / com:Sub> cycloalkyl ring, which is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-1,3-dione; the C<com:Sub>3-8< / com:Sub> cycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[162] In an embodiment of the present disclosure, <com:Math><semantics>R31<annotation encoding="application / x-tex">R_{31}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R32<annotation encoding="application / x-tex">R_{32}< / annotation>< / semantics>< / com:Math> form together with the carbon atom adjacent thereto a C<com:Sub>3-8< / com:Sub> cycloalkyl ring, which is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-1,3-dione; the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[163] In an embodiment of the present disclosure, <com:Math><semantics>R21<annotation encoding="application / x-tex">R_{21}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R31<annotation encoding="application / x-tex">R_{31}< / annotation>< / semantics>< / com:Math> form together with the carbon atom adjacent thereto a C<com:Sub>3-8< / com:Sub> cycloalkyl ring, which is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-1,3-dione; the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S. 164 In an embodiment of the present disclosure, R<com:Sub>11< / com:Sub> and R<com:Sub>31< / com:Sub> form together with the atom adjacent thereto a C<com:Sub>3-8< / com:Sub> cycloalkyl ring, which is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-1,3-dione; the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[165] In an embodiment of the present disclosure, R<com:Sub>23< / com:Sub> and R<com:Sub>24< / com:Sub> form together with the carbon atom adjacent thereto a C<com:Sub>3-8< / com:Sub> cycloalkyl ring, which is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-1,3-dione; the <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S. 166 In an embodiment of the present disclosure, R<com:Sub>3< / com:Sub> and R<com:Sub>4< / com:Sub> form together with the carbon atom adjacent thereto a 3- to 6-membered heterocycloalkyl ring, which is selected from aziridine, ethylene oxide, azetidine, oxetane, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine, thiomorpholine-1,1-dioxide and tetrahydropyran; the 3- to 6-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[167] In an embodiment of the present disclosure, R<com:Sub>5< / com:Sub> and R<com:Sub>6< / com:Sub> form together with the carbon atom adjacent thereto a 3- to 6-membered heterocycloalkyl ring, which is selected from aziridine, ethylene oxide, azetidine, oxetane, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine, thiomorpholine-1,1-dioxide and tetrahydropyran; the 3- to 6-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[168] In an embodiment of the present disclosure, R<com:Sub>4< / com:Sub> and R<com:Sub>5< / com:Sub> form together with the carbon atom adjacent thereto a 3- to 6-membered heterocycloalkyl ring, which is selected from aziridine, ethylene oxide, azetidine, oxetane, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine, thiomorpholine-1,1-dioxide and tetrahydropyran; the 3- to 6-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[169] In an embodiment of the present disclosure, <com:Math><semantics>R21<annotation encoding="application / x-tex">R_{21}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R22<annotation encoding="application / x-tex">R_{22}< / annotation>< / semantics>< / com:Math> form together with the carbon atom adjacent thereto a 3- to 6-membered heterocycloalkyl ring, which is selected from aziridine, ethylene oxide, azetidine, oxetane, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine, thiomorpholine-1,1-dioxide and tetrahydropyran; the 3- to 6-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[170] In an embodiment of the present disclosure, <com:Math><semantics>R31<annotation encoding="application / x-tex">R_{31}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R32<annotation encoding="application / x-tex">R_{32}< / annotation>< / semantics>< / com:Math> form together with the carbon atom adjacent thereto a 3- to 6-membered heterocycloalkyl ring, which is selected from aziridine, ethylene oxide, azetidine, oxetane, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine, thiomorpholine-1,1-dioxide and tetrahydropyran; the 3- to 6-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[171] In an embodiment of the present disclosure, <com:Math><semantics>R21<annotation encoding="application / x-tex">R_{21}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R31<annotation encoding="application / x-tex">R_{31}< / annotation>< / semantics>< / com:Math> form together with the carbon atom adjacent thereto a 3- to 6-membered heterocycloalkyl ring, which is selected from aziridine, ethylene oxide, azetidine, oxetane, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine, thiomorpholine-1,1-dioxide and tetrahydropyran; the 3- to 6-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[172] In an embodiment of the present disclosure, R<com:Sub>11< / com:Sub> and R<com:Sub>31< / com:Sub> are connected form together to form a 3- to 6-membered heterocycloalkyl ring, which is selected from aziridine, ethylene oxide, azetidine, oxetane, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine, thiomorpholine-1,1-dioxide and tetrahydropyran; the 3- to 6- membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[173] In an embodiment of the present disclosure, <com:Math><semantics>R23<annotation encoding="application / x-tex">R_{23}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R24<annotation encoding="application / x-tex">R_{24}< / annotation>< / semantics>< / com:Math> form together with the carbon atom adjacent thereto a 3- to 6-membered heterocycloalkyl ring, which is selected from aziridine, ethylene oxide, azetidine, oxetane, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine, thiomorpholine-1,1-dioxide and tetrahydropyran; the 3- to 6-membered heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[174] In an embodiment of the present disclosure, R<com:Sub>24< / com:Sub> and R<com:Sub>33< / com:Sub> form together with the atom adjacent thereto a 3- to 6-membered nitrogen-containing heterocycloalkyl ring, which is selected from aziridine, azetidine, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine and thiomorpholine-1,1-dioxide; the 3- to 6-membered nitrogen-containing heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[175] In an embodiment of the present disclosure, R<com:Sub>14< / com:Sub> and R<com:Sub>33< / com:Sub> form together with the atom adjacent thereto a 3- to 6-membered nitrogen-containing heterocycloalkyl ring, which is selected from aziridine, azetidine, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine and thiomorpholine-1,1-dioxide; the 3- to 6-membered nitrogen-containing heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[176] In an embodiment of the present disclosure, the 3- to 6-membered heterocycloalkyl is selected from the following structures: [Image disponible dans le document PDF, Image available in the PDF document] membered heterocycloalkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S. <com:Math><semantics>⌈177⌉<annotation encoding="application / x-tex">\lceil 177 \rceil< / annotation>< / semantics>< / com:Math> In an embodiment of the present disclosure, the 3- to 8-membered nitrogen-containing heterocycloalkyl ring formed by R<com:Sub>a0< / com:Sub> and R<com:Sub>b0< / com:Sub> form together with the nitrogen atom adjacent thereto, or the 3- to 8-membered nitrogen-containing heterocycloalkyl ring formed by R<com:Sub>a0< / com:Sub>' and R<com:Sub>b0< / com:Sub>' form [Image disponible dans le document PDF, Image available in the PDF document] together with the nitrogen atom adjacent thereto is selected from the following structures: , [Image disponible dans le document PDF, Image available in the PDF document] above 3- to 8-membered nitrogen-containing heterocycloalkyl ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

[178] In an embodiment of the present disclosure, in each formula, R<com:Sub>1< / com:Sub>, R<com:Sub>2< / com:Sub>, R<com:Sub>3< / com:Sub>, R<com:Sub>4< / com:Sub>, R<com:Sub>5< / com:Sub>, R<com:Sub>6< / com:Sub>, A and B are each independently the corresponding groups in each specific compound in the embodiment.

[179] In an embodiment of the present disclosure, the compound of formula (I) has a structure selected from table A.

[180] Table A [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]

[181] In an embodiment of the present disclosure, the compound of formula (I) is selected from the compounds prepared in the embodiments of the present application. For example, the compound is selected from compounds Z1 to Z85, Z93, Z94, Z96, Z97, Z98, and Z102.

[182] In a second aspect, the present disclosure provides a pharmaceutical composition, wherein the pharmaceutical composition comprises the compound or the pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof described in the first aspect of the present disclosure; and a pharmaceutically acceptable carrier.

[183] In a third aspect, the present disclosure provides a use of the compound or the pharmaceutically acceptable salt, the stereoisomer, the solvate or the prodrug thereof described in the first aspect of the present disclosure, or the pharmaceutical composition described in the second aspect of the present disclosure in the manufacture of a medicament for preventing and / or treating of diseases.

[184] In an embodiment of the present disclosure, the diseases are selected from the group of stroke, inflammatory bowel disease, ulcerative colitis, Crohn's disease, psoriasis, rheumatoid arthritis, NASH and heart failure.

[185] In a fourth aspect, the present disclosure provides a use of the compound or the pharmaceutically acceptable salt, the stereoisomer, the solvate or the prodrug thereof described in the first aspect of the present disclosure, or the pharmaceutical composition described in the second aspect of the present disclosure in the manufacture of a selective inhibitor of RIPK1, wherein the selective inhibitor of RIPK1 is used to treat RIPK1-related diseases or conditions. 186 In an embodiment of the present disclosure, the RIPK1-related diseases or conditions include, but are not limited to, inflammatory disease, such as Crohn's disease and ulcerative colitis, inflammatory bowel disease, asthma, graft versus host disease, and chronic obstructive pulmonary disease; autoimmune disease, such as Graves disease, rheumatoid arthritis, systemic lupus erythematosus, and psoriasis; destructive bone disease, such as bone resorption disease, osteoarthritis, osteoporosis, and multiple myeloma-associated bone disease; proliferative disease, such as acute myeloid leukemia, and chronic myelocytic leukemia; angiogenesis disorder, such as angiogenesis disorder, including solid tumor, ocular neoangiogenesis and hemangioma of infant; infectious disease, such as septicemia, septic shock and shigellosis; neurodegenerative disease, such as Alzheimer's disease, Parkinson disease, amyotrophic lateral sclerosis, cerebral ischemia or neurodegenerative disease caused by traumatic injury; tumor and viral disease, such as metastatic melanoma, Kaposi's sarcoma, multiple myeloma, HIV infection and CMV retinitis, and AIDS.

[187] In an embodiment of the present disclosure, the RIPK1-related diseases or conditions include, but are not limited to, pancreatitis (acute or chronic), asthma, allergy, adult respiratory distress syndrome, chronic obstructive pulmonary disease, glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, chronic thyroiditis, Graves disease, autoimmune gastritis, diabetes, autoimmune hemolytic anemia, autoimmune neutropenia, thrombocytopenia, atopic dermatitis, chronic active hepatitis, myasthenia gravis, amyotrophic lateral sclerosis, multiple sclerosis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, psoriasis, graft versus host disease, inflammation caused by endotoxin, tuberculosis, atherosclerosis, muscle degeneration, cachexia, psoriatic arthritis, Reiter's syndrome, gout, traumatic arthritis, rubella arthritis, acute synovitis, pancreatic β cell disease; disease characterized by infiltration of large numbers of neutrophils; rheumatoid spondylitis, gouty arthritis and other arthritic conditions, cerebral malaria, chronic lung inflammation, silicosis, pulmonary sarcoma, bone resorption disease, allograft rejection, fever and myalgia caused by infection, cachexia secondary to infection, luteoid formation, scar tissue formation, ulcerative colitis, fever, influenza, osteoporosis, osteoarthritis, acute myeloid leukemia, chronic myelogenous leukemia, metastatic melanoma, Kaposi's sarcoma, multiple myeloma, septicemia, septic shock and shigellosis; Alzheimer's disease, Parkinson disease, neurodegenerative disease caused by cerebral ischemia or traumatic injury; angiogenesis disorder, including solid tumor, ocular neoangiogenesis and hemangioma of infant; viral disease, including acute hepatitis infection (including hepatitis A, hepatitis B and hepatitis C), HIV infection and CMV retinitis, AIDS, ARC or malignant tumor and herpes; stroke, myocardial ischemia, stroke heart attack, organ ischemia, vascular proliferation, heart and kidney reperfusion injury, thrombosis, cardiac hypertrophy, thrombin-induced platelet aggregation, endotoxemia and / or toxic shock syndrome, conditions related to prostaglandin endoperoxidase synthase-2, and pemphigus vulgaris.

[188] In an embodiment of the present disclosure, the RIPK1-related diseases or conditions are selected from stroke, inflammatory bowel disease, Crohn's disease and ulcerative colitis, allograft rejection, rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis and pemphigus vulgaris. Alternatively, the conditions are preferably selected from ischemia reperfusion injury, including cerebral ischemia reperfusion injury caused by stroke, and myocardial ischemia reperfusion injury caused by myocardial infarction.

[189] It should be understood that, within the scope of the present disclosure, each of the above- mentioned technical features of the present disclosure and each of the technical features specifically described hereinafter (e.g., examples) may be combined with each other to constitute a new or preferred technical solution. Due to space limitations, it will not be repeated herein.

[190] Definitions

[191] As used herein, the term "heteroatom" is selected from nitrogen, oxygen or sulfur, wherein the nitrogen can be optionally substituted, and the sulfur is also optionally substituted, for example oxidized, i.e. forming <com:Math><semantics>S(O)t3<annotation encoding="application / x-tex">S(O)_{t3}< / annotation>< / semantics>< / com:Math> (where t3 is an integer of 0 to 2).

[192] As used herein, when a group such as an alkyl group is in the middle of a structural formula, the group denotes an alkylene group; for example, alkyl for alkylene, etc.

[193] As used herein, the term "alkyl" refers to a chain (straight or branched) saturated aliphatic hydrocarbon group. The term "alkyl" may be straight or branched alkyl containing 1 to 20 carbon atoms (<com:Math><semantics>C1−20<annotation encoding="application / x-tex">C_{1-20}< / annotation>< / semantics>< / com:Math> alkyl), preferably alkyl containing 1 to 12 carbon atoms (<com:Math><semantics>C1−12<annotation encoding="application / x-tex">C_{1-12}< / annotation>< / semantics>< / com:Math> alkyl), and non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 2-methylbutyl, 3- methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2- dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, n-heptyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5- methylhexyl, 2,3-dimethylpentyl, 2,4-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 2- ethylpentyl, 3-ethylpentyl, n-octyl, 2,3-dimethylhexyl, 2,4-dimethylhexyl, 2,5-dimethylhexyl, 2,2- dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, 2-ethylhexyl, 3-ethylhexyl, 4-ethylhexyl, 2- methyl-2-ethylpentyl, 2-methyl-3-ethylpentyl, n-nonyl, 2-methyl-2-ethylhexyl, 2-methyl-3- ethylhexyl, 2,2-diethylpentyl, n-decyl, 3,3-diethylhexyl, 2,2-diethylhexyl, various branched isomers thereof, etc. More preferably, the term "alkyl" is lower alkyl containing 1 to 6 carbon atoms (<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl), and non-limiting examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert- butyl, sec-butyl, n-pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, 1- ethylpropyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 2,2-dimethylbutyl, 1,3-dimethylbutyl, 2-ethylbutyl, 2- methylpentyl, 3-methylpentyl, 4-methylpentyl, 2,3-dimethylbutyl, etc. More preferably, the term "alkyl" is lower alkyl containing 1 to 3 carbon atoms (<com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl), and non-limiting examples include methyl, ethyl, n-propyl, isopropyl, etc. Alkyl may be substituted or non-substituted; and when alkyl is substituted, the substituents are preferably one or more groups as described in the present application.

[194] As used herein, the terms "cycloalkyl" and "cycloalkyl ring" can be used interchangeably, and refer to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon group. The term "cycloalkyl" may be cycloalkyl containing 3 to 20 carbon atoms (C<com:Sub>3-20< / com:Sub> cycloalkyl), preferably cycloalkyl containing 3 to 12 carbon atoms (<com:Math><semantics>C3−12<annotation encoding="application / x-tex">C_{3-12}< / annotation>< / semantics>< / com:Math> cycloalkyl), more preferably cycloalkyl containing 3 to 10 carbon atoms (<com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> cycloalkyl), and more preferably cycloalkyl containing 3 to 6 carbon atoms (<com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl). The ring carbon atoms of the cycloalkyl may be optionally substituted with 1, 2, or 3 oxo groups to form a cyclic ketone structure.

[195] When the cycloalkyl is monocyclic cycloalkyl, monocyclic cycloalkyl containing 3 to 8 ring carbon atoms (i.e., 3- to 8-membered or C<com:Sub>3-8< / com:Sub> cycloalkyl) is preferred; "C<com:Sub>3-8< / com:Sub> monocyclic cycloalkyl" and "C<com:Sub>3-8< / com:Sub> cycloalkyl" can be used interchangeably herein; monocyclic cycloalkyl containing 3 to 6 ring carbon atoms (i.e., 3- to 6-membered or C<com:Sub>3-6< / com:Sub> cycloalkyl) is more preferred; non-limiting examples of monocyclic cycloalkyl (or <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl) include cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cycloheptyl, cycloheptatrienyl, cyclooctyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, cyclohexane-1,3-dione, etc.

[196] Typically, cycloalkyl containing 3 to 6 carbon atoms (C<com:Sub>3-6< / com:Sub> cycloalkyl) refers to monocyclic cycloalkyl (C<com:Sub>3-6< / com:Sub>monocyclic cycloalkyl). As used herein, "3- to 6-membered monocyclic", "3- to 6- membered monocyclic cycloalkyl", "C<com:Sub>3-6< / com:Sub> monocyclic cycloalkyl" and "C<com:Sub>3-6< / com:Sub> cycloalkyl" can be used interchangeably, and refer to a saturated or partially unsaturated full-carbon monocyclic ring containing 3 to 6 ring atoms. The ring carbon atoms of the monocyclic ring may be optionally substituted with 1, 2, or 3 oxo groups to form a cyclic ketone structure. Examples of 3- to 6- membered monocyclic ring include (but are not limited to): cyclopropyl ring, cyclobutyl ring, cyclopentyl ring, cyclopentenyl ring, cyclohexyl ring, cyclohexenyl ring, cyclohexadienyl ring, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, cyclohexane-1,3-dione, etc.

[197] In the case of polycyclic cycloalkyl, the polycyclic cycloalkyl includes spirocycloalkyl, fused cycloalkyl and bridged cycloalkyl.

[198] As used herein, the term "spirocycloalkyl" refers to a saturated or partially unsaturated polycyclic cyclic hydrocarbon group, wherein the rings in the system share one carbon atom (called spiro atom). The term "saturated spirocycloalkyl" refers to spirocycloalkyl containing no unsaturated bonds. The term "partially unsaturated spirocycloalkyl" refers to spirocycloalkyl that may contain one or more double bonds in each monocyclic ring, but none of the rings has a fully conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. The term "spirocycloalkyl" may be spirocycloalkyl containing 5 to 20 ring carbon atoms (i.e. 5- to 20-membered or C<com:Sub>5-20< / com:Sub> spirocycloalkyl), in which the 3- to 8- membered (i.e. containing 3 to 8 ring carbon atoms or C<com:Sub>3-8< / com:Sub>) monocyclic rings share a carbon atom (called spiro atom). 6- to 14-membered spirocycloalkyl is preferred, and 7- to 11-membered spirocycloalkyl is more preferred. According to the number of shared spiro atoms between rings, spirocycloalkyl can be divided into monospirocycloalkyl, bispirocycloalkyl or polyspirocycloalkyl; monospirocycloalkyl and bispirocycloalkyl are preferred; and 7-membered (4-membered monocyclic / 4-membered monocyclic), 8-membered (4-membered monocyclic / 5-membered monocyclic), 9-membered (4-membered monocyclic / 6-membered monocyclic, 5-membered monocyclic / 5-membered monocyclic), 10-membered (5-membered monocyclic / 6-membered monocyclic) or 11-membered (6-membered monocyclic / 6-membered monocyclic) monospirocycloalkyl is more preferred. Non-limiting examples of spirocycloalkyl (or 7- to 11- membered spirocycloalkyl) include: [Image disponible dans le document PDF, Image available in the PDF document] .

[199] As used herein, the term "fused cycloalkyl" refers to a saturated or partially unsaturated polycyclic cyclic hydrocarbon group, wherein each ring in the system shares an adjacent pair of carbon atoms with another ring in the system. The term "saturated fused cycloalkyl" refers to fused cycloalkyl containing no unsaturated bonds. The term "partially unsaturated fused cycloalkyl" refers to fused cycloalkyl in which one or more rings may contain one or more double bonds, but none of the rings has a fully conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. The term "fused cycloalkyl" may be fused cycloalkyl containing 5 to 20 ring carbon atoms (i.e., 5- to 20-membered or C<com:Sub>5-20< / com:Sub>). 6- to 14- membered fused cycloalkyl is preferred, and 6- to 10-membered fused cycloalkyl is more preferred. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic fused cycloalkyl, preferably bicyclic or tricyclic, and more preferably 8-membered (5- membered monocyclic ring fused to 5-membered monocyclic ring), 9-membered (5-membered monocyclic ring fused to 6-membered monocyclic ring) or 10-membered (6-membered monocyclic ring fused to 6-membered monocyclic ring) bicyclic fused cycloalkyl. Non-limiting examples of fused cycloalkyl (or 6- to 10-membered fused cycloalkyl) include: [Image disponible dans le document PDF, Image available in the PDF document]

[200] As used herein, the term "bridged cycloalkyl" refers to a saturated or partially unsaturated polycyclic cyclic hydrocarbon group, wherein any two rings in the system share two carbon atoms that are not directly connected. The term "saturated bridged cycloalkyl" refers to bridged cycloalkyl containing no unsaturated bonds. The term "partially unsaturated bridged cycloalkyl" refers to bridged cycloalkyl containing one or more double bonds, but none of the rings has a fully conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. The term "bridged cycloalkyl" may be bridged cycloalkyl containing 5 to 20 ring carbon atoms (i.e., 5- to 20-membered or <com:Math><semantics>C5−20<annotation encoding="application / x-tex">C_{5-20}< / annotation>< / semantics>< / com:Math>). 6- to 14-membered bridged cycloalkyl is preferred, and 7- to 10-membered bridged cycloalkyl is more preferred. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic bridged cycloalkyl, preferably bicyclic, tricyclic or tetracyclic, and more preferably bicyclic or tricyclic. Non-limiting examples of bridged cycloalkyl include: WSLEGAL\092120\00005\36981746v1 [Image disponible dans le document PDF, Image available in the PDF document]

[201] The cycloalkyl ring can be fused to aryl, heteroaryl or heterocycloalkyl ring, wherein the ring connected to the parent structure is a cycloalkyl ring, and non-limiting examples include indanyl, tetrahydronaphthyl, benzocycloheptanyl, etc. Cycloalkyl may be optionally substituted or non-substituted; and when cycloalkyl is substituted, the substituents are preferably one or more groups as described in the present application.

[202] As used herein, the term "C<com:Sub>2-8< / com:Sub> alkenyl" refers to alkyl as defined above composed of 2 to 8 carbon atoms and at least one carbon-carbon double bond, preferably C<com:Sub>2-6< / com:Sub>alkenyl composed of 2 to 6 carbon atoms and 1 to 2 carbon-carbon double bonds, and more preferably <com:Math><semantics>C2−4<annotation encoding="application / x-tex">C_{2-4}< / annotation>< / semantics>< / com:Math> alkenyl composed of 2 to 4 carbon atoms and 1 to 2 carbon-carbon double bonds, such as vinyl, 1-propenyl, 2-propenyl, 1-, 2- or 3-butenyl, etc. Alkenyl may be substituted or non-substituted; and when alkenyl is substituted, the substituents are preferred one or more groups as described in the present application.

[203] As used herein, the term "<com:Math><semantics>C2−8<annotation encoding="application / x-tex">C_{2-8}< / annotation>< / semantics>< / com:Math> alkynyl" refers to alkyl as defined above composed of 2 to 8 carbon atoms and at least one carbon-carbon triple bond, preferably C<com:Sub>2-6< / com:Sub> alkynyl composed of 2 to 6 carbon atoms and 1 to 2 carbon-carbon triple bonds, and more preferably C<com:Sub>2-4< / com:Sub> alkynyl composed of 2 to 4 carbon atoms and 1 to 2 carbon-carbon triple bonds, such as ethynyl, 1-propynyl, 2- propynyl, 1-, 2- or 3-butynyl, etc. Alkynyl may be substituted or non-substituted; and when alkynyl is substituted, the substituents are preferred one or more groups as described in the present application.

[204] As used herein, the term "heterocycloalkyl" and "heterocycloalkyl ring" can be used interchangeably, and refer to a saturated or partially unsaturated monocyclic or polycyclic cyclic hydrocarbon group, wherein one or more (preferably 1 to 4, 1 to 3, or 1 to 2) ring atoms are the heteroatoms selected from nitrogen, oxygen or S(O)<com:Sub>13< / com:Sub> (where t3 is an integer of 0 to 2), with the ring part of-O-O-, -O-S- or-S-S- being excluded, and the rest of the ring atoms being carbon atoms. The term "heterocycloalkyl" may be heterocycloalkyl containing 3 to 20 ring atoms (i.e., 3- to 20- membered heterocycloalkyl), preferably 3- to 12-membered heterocycloalkyl, more preferably 3- to 10-membered heterocycloalkyl, and more preferably 3- to 6-membered heterocycloalkyl, wherein one or more (preferably 1 to 4) ring atoms are the heteroatoms selected from nitrogen, oxygen or S(O)<com:Sub>t3< / com:Sub> (where t3 is an integer of 0 to 2), with the ring part of-O-O-, -O-S- or-S-S- being excluded, and the rest of the ring atoms being carbon atoms. Nitrogen atoms may be substituted or unsubstituted (i.e., N or NR, R being hydrogen or any of the substituents already defined herein). The ring carbon atoms of the heterocycloalkyl may be optionally substituted with 1, 2, or 3 oxo groups to form a cyclic ketone, cyclic lactone or cyclolactam structure.

[205] As used herein, with regard to "3- to 20-membered heterocycloalkyl", "3- to 12- membered heterocycloalkyl", "3- to 10-membered heterocycloalkyl" or "3- to 6-membered heterocycloalkyl", when these heterocycloalkyl groups are 3-membered heterocycloalkyl groups and contain only one heteroatom as a ring atom, the heteroatom is not a nitrogen atom.

[206] In some embodiments of the present disclosure, "heterocycloalkyl" refers to monocyclic heterocycloalkyl, wherein the monocyclic heterocycloalkyl is saturated or partially unsaturated, preferably monocyclic heterocycloalkyl containing 3 to 8 ring atoms (i.e., 3- to 8-membered), of which 1, 2, or 3 are heteroatoms, more preferably monocyclic heterocycloalkyl containing 3 to 6 ring atoms (i.e., 3- to 6-membered), of which 1, 2, or 3 are heteroatoms, and most preferably monocyclic heterocycloalkyl containing 5 or 6 ring atoms (i.e., 5- or 6-membered), of which 1, 2, or 3 are heteroatoms. As used herein, the term "3- to 6-membered heterocycloalkyl" and "3- to 6- membered monocyclic heterocycloalkyl" can be used interchangeably, and the term "5- or 6- membered heterocycloalkyl" and "5- or 6-membered monocyclic heterocycloalkyl" can be used interchangeably. When the heteroatom is a nitrogen atom, the nitrogen atom may be substituted or unsubstituted (i.e., N or NR, R being hydrogen or other substituents already defined herein). When the heteroatom is a sulfur atom, the sulfur atom may be optionally oxidized (i.e., <com:Math><semantics>S(O)t3<annotation encoding="application / x-tex">S(O)_{t3}< / annotation>< / semantics>< / com:Math>, t3 is an integer of 0 to 2). The ring carbon atoms of the monocyclic heterocycloalkyl may be optionally substituted with 1, 2, or 3 oxo groups to form a cyclic ketone, cyclic lactone or cyclolactam structure. Non-limiting examples of monocyclic heterocycloalkyl include: aziridine, ethylene oxide, azetidine, azetidine-2-one, oxetane, oxetane-2-one, oxazolidine, pyrrolidine-2-one, pyrrolidine-2,5-dione, 1,3-dioxolane, dihydrofuran-2(3H)-one, dihydrofuran-2,5-dione, piperidine-2-one, piperidine-2,6- dione, tetrahydro-2H-pyran-2-one, imidazolidine, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, 1,3-dioxolane-2-one, oxazolidine-2-one, imidazolidine-2-one, piperidine, piperazine, piperazine-2-one, morpholine, morpholine-3-one, morpholine-2-one, thiomorpholine-3- one 1,1-dioxide, thiomorpholine, thiomorpholine-1,1-dioxide, tetrahydropyran, 1,2- dihydroazetidine, 1,2-dihydrooxetadiene, 2,5-dihydro-1H-pyrrole, 2,5-dihydrofuran, 2,3- dihydrofuran, 2,3-dihydro-1H-pyrrole, 3,4-dihydro-2H-pyran, 1,2,3,4-tetrahydropyridine, 3,6- dihydro-2H-pyran, 1,2,3,6-tetrahydropyridine, 1,3-oxazinane, hexahydropyrimidine, 1,4-dioxane, tetrahydropyrimidine-2(1H)-one, 1,4-dioxane-2-one, 5,6-dihydro-2H-pyran-2-one, 5,6- dihydropyrimidine-4(3H)-one, 3,4-dihydropyridine-2(1H)-one, 5,6-dihydropyridine-2(1H)-one, 5,6-dihydropyrimidine-4(1H)-one, pyrimidine-4(3H)-one, pyrimidine-4(1H)-one, 4,5-dihydro-1H- imidazole, 2,3-dihydro-1H-imidazole, 2,3-dihydroxazole, 1,3-dioxolene, 2,3-dihydrothiophene, 2,5-dihydrothiophene, 3,4-dihydro-2H-1,4-oxazine, 3,4-dihydro-2H-1,4-thiazide 1,1-dioxide, 1,2,3,4-tetrahydropyrazine, 1,3-dihydro-2H-pyrrole-2-one, 1,5-dihydro-2H-pyrrole-2-one, 1H- pyrrole-2,5-dione, furan-2(3H)-one, furan-2(5H)-one, 1,3-dioxolene-2-one, oxazole-2(3H)-one, 1,3-dihydro-2H-imidazole-2-one, furan-2,5-dione, 3,6-dihydropyridine-2(1H)-one, pyridine-2,6- (1H, 3H)-dione, 5,6-dihydro-2H-pyran-2-one, 3,6-dihydro-2H-pyran-2-one, 3,4-dihydro-2H-1,3- oxazine, 3,6-dihydro-2H-1,3-oxazine, 1,2,3,4-tetrahydropyrimidine, etc.

[207] Typically, 3- to 6-membered heterocycloalkyl refers to 3- to 6-membered monocyclic heterocycloalkyl. As used herein, "3- to 6-membered monocyclic heterocyclic ring" or "3- to 6- membered monocyclic heterocycloalkyl" can be used interchangeably, and refers to 3- to 6- membered, preferably 4- to 6-membered, and more preferably 5- to 6-membered, saturated or partially unsaturated monocyclic ring, in which 1, 2 or 3 carbon atoms are substituted with heteroatoms selected from nitrogen, oxygen or S(O)<com:Sub>t5< / com:Sub> (where t5 is an integer of 0 to 2), with the ring part of-O-O-, -O-S- or-S-S- being excluded, and the rest of the ring atoms being carbon atoms. The ring carbon atoms of the monocyclic heterocyclic ring may be optionally substituted with 1, 2, or 3 oxo groups to form a cyclic ketone, cyclic lactone or cyclolactam structure. Examples of 3- to 6- membered monocyclic heterocyclic ring include (but are not limited to) aziridine, ethylene oxide, azetidine, oxetane, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, pyrroline, oxazolidine, piperazine, dioxolane, dioxane, morpholine, thiomorpholine, thiomorpholine-1,1- dioxide, tetrahydropyran, 1,2-dihydroazetidine, 1,2-dihydrooxetadiene, 2,5-dihydro-1H-pyrrole, 2,5-dihydrofuran, 2,3-dihydrofuran, 2,3-dihydro-1H-pyrrole, 3,4-dihydro-2H-pyran, 1,2,3,4- tetrahydropyridine, 3,6-dihydro-2H-pyran, 1,2,3,6-tetrahydropyridine, etc.

[208] In an embodiment of the present disclosure, the monocyclic heterocycloalkyl is 3- to 6- membered monocyclic heterocycloalkyl or 4- to 6-membered monocyclic heterocycloalkyl, and non-limiting examples of the 3- to 6-membered monocyclic heterocycloalkyl or 4- to 6-membered monocyclic heterocycloalkyl include: NH, O, HN NH, HN O OOO [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]

[209] The above-mentioned two ring atoms connected to the monocyclic heterocycloalkyl, including C-C and N-C, can be optionally fused with cycloalkyl, heterocycloalkyl, aryl or heteroaryl as defined in the present disclosure, such as monocyclic cycloalkyl ring, monocyclic heterocycloalkyl ring, monoaryl ring, and 5- or -6-membered monocyclic heteroaryl ring, to form a fused polycyclic ring, and the two ring atoms connected to the monocyclic heterocycloalkyl, which are together with other rings to form fused rings, are preferably C-C.

[210] As used herein, "3- to 6-membered nitrogen-containing heterocycloalkyl" means that one of the ring atoms of the 3- to 6-membered heterocycloalkyl must be nitrogen atom, and the rest of the ring atoms are all carbon atoms, or 0, 1 or 2 of the rest of the ring atoms is each independently heteroatom selected from nitrogen, oxygen or sulfur. Preferably, the "3- to 6-membered nitrogen- containing heterocycloalkyl" is connected to the rest of the molecule via the nitrogen atom that must be contained in the molecule. WSLEGAL\092120\00005\36981746v1

[211] In some embodiments of the present disclosure, "heterocycloalkyl" refers to polycyclic heterocycloalkyl, including spiroheterocycloalkyl, fused heterocycloalkyl and bridged heterocycloalkyl.

[212] As used herein, the term "spiroheterocycloalkyl" refers to saturated or partially unsaturated polycyclic heterocycloalkyl, wherein one atom (called a spiro atom) is shared between the monocyclic rings in the system, and one or more (for example, 1 to 4, or 1 to 3, or 1 to 2) of the ring atoms are heteroatoms selected from nitrogen, oxygen or S(O)<com:Sub>t4< / com:Sub> (wherein t4 is an integer of 0 to 2), and the rest of the ring atoms are carbon. The term "saturated spiroheterocycloalkyl" refers to a spiroheterocycloalkyl system containing no unsaturated bonds. The term "partially unsaturated spiroheterocycloalkyl" means that one or more rings in the spiroheterocycloalkyl system may contain one or more double bonds, but none of the rings has a fully conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. The term "spiroheterocycloalkyl" may be a spiroheterocycloalkyl containing 5 to 20 ring atoms (i.e., 5- to 20-membered), wherein one atom (called a spiro atom) is shared between 3- to 8-membered monocyclic rings (i.e., containing 3 to 8 ring atoms), and the spiroheterocycloalkyl is preferably 6- to 14-membered spiroheterocycloalkyl, and more preferably 7- to 11-membered spiroheterocycloalkyl; and one or more of the ring atoms are heteroatoms selected from nitrogen, oxygen or <com:Math><semantics>S(O)t4<annotation encoding="application / x-tex">S(O)_{t4}< / annotation>< / semantics>< / com:Math> (wherein t4 is an integer of 0 to 2), and the rest of the ring atoms are carbon. When the heteroatom is a nitrogen atom, the nitrogen atom may be substituted or unsubstituted (i.e., N or NR, R being hydrogen or other substituents already defined herein). Each monocyclic ring can contain one or more double bonds, but none of the rings has a fully conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. According to the number of shared spiro atoms between the rings, the spiroheterocycloalkyl is divided into monospiroheterocycloalkyl, bisspiroheterocycloalkyl or polyspiroheterocycloalkyl, preferably monospiroheterocycloalkyl and bisspiroheterocycloalkyl. More preferably, 7-membered (4-membered monocyclic ring / 4-membered monocyclic ring), 8-membered (4-membered monocyclic ring / 5-membered monocyclic ring), 9-membered (4-membered monocyclic ring / 6- membered monocyclic ring, 5-membered monocyclic ring / 5-membered monocyclic ring), 10- membered (5-membered monocyclic ring / 6-membered monocyclic ring), or 11-membered (6- membered monocyclic ring / 6-membered monocyclic ring) monospiroheterocycloalkyl. The non- limiting examples of spiroheterocycloalkyl include: [Image disponible dans le document PDF, Image available in the PDF document]

[213] As used herein, the term "fused heterocycloalkyl" refers to saturated or partially unsaturated polycyclic heterocycloalkyl, wherein each ring in the system shares an adjacent pair of atoms with other rings in the system, and one or more (for example, 1 to 4, or 1 to 3, or 1 to 2) of the ring atoms in the system are heteroatoms selected from nitrogen, oxygen or S(O)<com:Sub>t4< / com:Sub> (wherein t4 is an integer of 0 to 2), and the rest of the ring atoms are carbon. The term "saturated fused heterocycloalkyl" refers to a fused heterocycloalkyl system containing no unsaturated bonds. The term "partially unsaturated fused heterocycloalkyl" means that one or more rings in the fused heterocycloalkyl system may contain one or more double bonds, but none of the rings has a fully conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. The term "fused heterocycloalkyl" may be a fused heterocycloalkyl containing 5 to 20 ring atoms (i.e., 5- to 20-membered), preferably 6- to 14-memberedfused heterocycloalkyl, more preferably 6- to 10-membered fused heterocycloalkyl, and more preferably 8- to 10-membered fused heterocycloalkyl; and one or more of the ring atoms in the system are heteroatoms selected from nitrogen, oxygen or <com:Math><semantics>S(O)t4<annotation encoding="application / x-tex">S(O)_{t4}< / annotation>< / semantics>< / com:Math> (wherein t4 is an integer of 0 to 2), and the rest of the ring atoms are carbon. When the heteroatom is a nitrogen atom, the nitrogen atom may be substituted or unsubstituted (i.e., N or NR, R being hydrogen or other substituents already defined herein). According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic fused heterocycloalkyl, preferably bicyclic or tricyclic, and more preferably 8-membered (5-membered monocyclic ring fused with 5-membered monocyclic ring), 9-membered (5-membered monocyclic ring fused with 6-membered monocyclic ring) or 10-membered (6- membered monocyclic ring fused with 6-membered monocyclic ring) bicyclic fused [Image disponible dans le document PDF, Image available in the PDF document] heterocycloalkyl. The non-limiting examples of fused heterocycloalkyl include: [Image disponible dans le document PDF, Image available in the PDF document]

[214] As used herein, the term "bridged heterocycloalkyl" refers to saturated or partially unsaturated polycyclic heterocycloalkyl, wherein any two rings in the system share two atoms that are not directly connected, and one or more (for example, 1 to 4, or 1 to 3, or 1 to 2) of the ring atoms are heteroatoms selected from nitrogen, oxygen or S(O)<com:Sub>t3< / com:Sub> (wherein t3 is an integer of 0 to 2), and the rest of the ring atoms are carbon. The term "saturated bridged heterocycloalkyl" refers to a bridged heterocycloalkyl system containing no unsaturated bonds. The term "partially unsaturated bridged heterocycloalkyl" means that one or more rings in the bridged heterocycloalkyl system may contain one or more double bonds, but none of the rings has a fully conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. The term "bridged heterocycloalkyl" may be a bridged heterocycloalkyl containing 5 to 20 ring atoms (i.e., 5- to 20-membered), preferably 6- to 14-membered bridged heterocycloalkyl, and more preferably 7- to 10-membered bridged heterocycloalkyl; and one or more (for example, 1 to 4, or 1 to 3, or 1 to 2) of the ring atoms are heteroatoms selected from nitrogen, oxygen or S(O)<com:Sub>t3< / com:Sub> (wherein t3 is an integer of 0 to 2), and the rest of the ring atoms are carbon. According to the number of constituent rings, it can be divided into bicyclic, tricyclic, tetracyclic or polycyclic bridged heterocycloalkyl, preferably bicyclic, tricyclic or tetracyclic, and more preferably bicyclic or tricyclic. The non-limiting examples of bridged heterocycloalkyl include: [Image disponible dans le document PDF, Image available in the PDF document]

[215] In the present disclosure, the above-mentioned various heterocycloalkyl groups may be optionally substituted or unsubstituted; when substituted, the substituents are preferably one or more groups as described in the present application. |216| As used herein, in "spiroheterocycloalkyl", "bridged heterocycloalkyl" or "fused heterocycloalkyl", when the ring containing a heteroatom is a 3-membered ring and contains only one heteroatom as a ring atom, the heteroatom is not a nitrogen atom.

[217] As used herein, the terms "aryl", "aryl ring" and "aromatic ring" are used interchangeably and refer to fully unsaturated aliphatic hydrocarbon groups. It can be an all-carbon monocyclic ring containing 6 to 14 ring atoms (i.e., 6- to 14-membered or <com:Math><semantics>C6−14<annotation encoding="application / x-tex">C_{6-14}< / annotation>< / semantics>< / com:Math>), an all-carbon polycyclic ring (the rings are connected via covalent bonds, not by means of fusion) or an all-carbon fused polycyclic ring (that is, a ring that shares adjacent pairs of carbon atoms) group, wherein at least one ring in the ring system is aromatic, that is, it has a conjugated <com:Math><semantics>π<annotation encoding="application / x-tex">\pi< / annotation>< / semantics>< / com:Math>-electron system. Preferably, any local containing 6 to 10 ring carbon atoms (i.e., 6- to 10-membered or <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math>). Each ring in the ring system contains 5 or 6 ring atoms.

[218] In some embodiments of the present disclosure, "aryl" refers to a monoaryl or polyaryl ring, non-limiting examples of which include: phenyl, biphenyl, etc.

[219] In some embodiments of the present disclosure, "aryl" refers to an aromatic fused polycyclic ring, which is a polycyclic group in which monoaryl ring is fused with one or more monoaryl rings, non-limiting examples of which include: naphthyl, anthracenyl, etc. 1220 In some embodiments of the present disclosure, and ring described herein (e.g., monoary) ring, preferably phenyl) may be fused with one or more non-aromatic rings to form a polycyclic group, wherein the ring connected to the parent structure is an aromatic ring or a non-aromatic ring, and the non-aromatic ring includes but is not limited to: a 3- to 6-membered monocyclic heterocycloalkyl ring, preferably a 5- or -6-membered monocyclic heterocycloalkyl ring (the ring carbon atoms of the monocyclic heterocycloalkyl ring may be substituted by 1 to 2 oxo groups to form a cyclolactam or cyclic lactone structure); a 3- to 6-membered monocyclic cycloalkyl ring, preferably a 5- or 6-membered monocyclic cycloalkyl ring (the ring carbon atoms of the monocyclic cycloalkyl ring may be substituted by 1 or 2 oxo groups to form a cyclic ketone structure), etc. The polycyclic group in which the above-mentioned monoaryl ring is fused with one or more non- aromatic rings can be connected to other groups or the parent structure via a nitrogen atom or carbon atom, and the ring connected to the parent structure is a monoaryl ring or non-aromatic ring.

[221] As used herein, the phenyl is fused with a 5- or -6-membered monocyclic heterocycloalkyl ring to form a 9- or 10-membered bicyclic ring, which means that two adjacent substituent groups on the phenyl taken together with the ring atoms connecting them form a fused 5- or -6-membered monocyclic heterocycloalkyl ring, wherein the 5- or -6-membered monocyclic heterocycloalkyl ring is as defined herein, and the formed 9- or 10-membered bicyclic ring can also be called a 9- or 10- membered phenylheterocycloalkyl ring.

[222] As used herein, the phenyl is fused with a 5- or -6-membered monocyclic cycloalkyl ring to form a 9- or 10-membered bicyclic ring, which means that two adjacent substituent groups on the phenyl taken together with the ring atoms connecting them form a fused 5- or -6-membered monocyclic cycloalkyl ring, wherein the 5- or -6-membered monocyclic cycloalkyl ring is as defined herein, and the formed 9- or 10-membered bicyclic ring can also be called a 9- or 10- membered phenylcycloalkyl ring.

[223] In the present disclosure, the above-mentioned various aryl groups may be substituted or unsubstituted; when substituted, the substituents are preferably one or more groups as described in the present application. 224 As used herein, the term "heteroaryl", "heteroaryl ring" and "heteroaromatic ring" are used interchangeably and refer to fully unsaturated aliphatic hydrocarbon groups containing heteroatoms. It may be a monocyclic or fused polycyclic ring (that is, a ring that shares adjacent pairs of carbon atoms or heteroatoms) group which may contain 5 to 14 ring atoms (i.e., 5- to 14- membered), preferably 5 to 10 ring atoms (i.e., 5- to 10-membered), more preferably 5, 6, 8, 9 or 10 ring atoms, in which 1 to 4 heteroatoms are contained therein as ring atoms, and the heteroatoms are selected from oxygen, sulfur and nitrogen. The nitrogen and sulfur atoms can be optionally oxidized, and nitrogen atoms can be optionally quaternized. The heteroaryl preferably has 6, 10 or <com:Math><semantics>14π<annotation encoding="application / x-tex">14 \pi< / annotation>< / semantics>< / com:Math> electrons shared in the ring system. At least one ring in the ring system is aromatic.

[225] In some embodiments of the present disclosure, "heteroaryl" refers to monocyclic heteroaryl ring (preferably 5- or -6-membered monocyclic heteroaryl ring), non-limiting examples of which include: thiophene, N-alkylpyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine, pyrazine, etc.

[226] In some embodiments of the present disclosure, "heteroaryl" refers to fused polyheteroaryl ring (preferably 8- to 10-membered bicyclic heteroaryl ring). The fused polyheteroaryl ring includes both a polycyclic group (preferably a 9- or 10-membered bicyclic heteroaryl ring) in which a monoaryl ring (preferably phenyl) is fused with a monocyclic heteroaryl ring (preferably a 5- or -6-membered monocyclic heteroaryl ring), and a polycyclic group (preferably a 8- to 10-membered bicyclic heteroaryl ring) in which a monocyclic heteroaryl (preferably a 5- or -6-membered monocyclic heteroaryl) is fused with a monocyclic heteroaryl (preferably a 5- or -6-membered monocyclic heteroaryl).

[227] In some embodiments of the present disclosure, non-limiting examples of the monocyclic heteroaryl ring (preferably 5- or -6-membered monocyclic heteroaryl ring) that forms a fused [Image disponible dans le document PDF, Image available in the PDF document]

[228] The above-mentioned any two ring atoms connected to the monocyclic heteroaryl ring, including C-C, N-C and N-N, can be fused with cycloalkyl, heterocycloalkyl, aryl or heteroaryl as defined in the present disclosure, such as monocyclic cycloalkyl ring, monocyclic heterocycloalkyl ring, monoaryl ring, and 5- or -6-membered monocyclic heteroaryl ring, to form a fused polycyclic ring. The two adjacent ring atoms of the monocyclic heteroaryl ring forming a fused ring with other rings are preferably C-C, and the monocyclic heteroaryl ring includes the following forms without [Image disponible dans le document PDF, Image available in the PDF document]

[229] Non-limiting examples of fused polyheteroaryl rings include: benzo[d]isoxazole, 1H- indole, isoindole, 1H-benzo[d]imidazole, benzo[d]isothiazole, 1H-benzo[d][1,2,3]triazole, benzo[d]oxazole, benzo[d]thiazole, indazole, benzofuran, benzo[b]thiophene, quinoline, isoquinoline, quinazoline, quinoxaline, cinnoline, pyrido[3,2-d]pyrimidine, pyrido[2,3- d]pyrimidine, pyrido[3,4-d]pyrimidine, pyrido[4,3-d]pyrimidine, 1,8-naphthyridine, 1,7- naphthyridine, 1,6-naphthyridine, 1,5-naphthyridine, pyrazolo[1,5-a]pyrimidine, imidazolo[1,2- b|pyridazine, etc.

[230] The above-mentioned monocyclic heteroaryl, or a polycyclic group in which a monoaryl ring is fused with a monocyclic heteroaryl ring, or a polycyclic group in which a monocyclic heteroaryl is fused with a monocyclic heteroaryl may be connected to other groups or the parent structure via a nitrogen atom or carbon atom. In the case of a polycyclic group, the ring connected to the parent structure is a heteroaryl ring, an aryl ring, a monocyclic cycloalkyl ring or a monocyclic heterocycloalkyl ring, non-limiting examples of which include: [Image disponible dans le document PDF, Image available in the PDF document]

[231] In some embodiments of the present disclosure, the heteroaryl ring as described in the present disclosure (e.g., monocyclic heteroaryl ring, preferably 5- or 6-membered monocyclic heteroaryl ring) may be fused with one or more non-aromatic rings to form a polycyclic group, wherein the ring connected to the parent structure is a heteroaryl ring or a non-aromatic ring, and the non-aromatic ring includes but is not limited to: a 3- to 6-membered (preferably a 5- or 6- membered) monocyclic heterocycloalkyl ring (the ring carbon atoms of the monocyclic heterocycloalkyl ring may be substituted by 1 to 2 oxo groups to form a cyclolactam or cyclic lactone structure); a 3- to 6-membered (preferably a 5- or -6-membered) monocyclic cycloalkyl ring (the ring carbon atoms of the monocyclic cycloalkyl ring may be substituted by 1 or 2 oxo groups to form a cyclic ketone structure), etc.

[232] The polycyclic group in which the above-mentioned monocyclic heteroaryl ring is fused with one or more non-aromatic rings can be connected to other groups or the parent structure via a nitrogen atom or carbon atom, and the ring connected to the parent structure is a heteroaryl ring or a non-aromatic ring.

[233] As used herein, the 5- or 6-membered monocyclic heteroaryl is fused with a 5- or -6- membered monocyclic heterocycloalkyl ring to form a 8- to 10-membered biheterocyclic ring, which means that two adjacent substituent groups on the 5- or 6-membered monocyclic heteroaryl together with the ring atoms connecting them form a fused 5- or -6-membered monocyclic heterocycloalkyl ring, and the 5- or -6-membered monocyclic heterocycloalkyl ring is as defined herein, and the formed 8- to 10-membered biheterocyclic ring can also be called a 8- to 10- membered heteroaryl heterocycloalkyl ring.

[234] As used herein, the 5- or 6-membered monocyclic heteroaryl is fused with a 5- or -6- membered monocyclic cycloalkyl ring to form a 8- to 10-membered biheterocyclic ring, which means that two adjacent substituent groups on the 5- or 6-membered monocyclic heteroaryl together with the ring atoms connecting them form a fused 5- or -6-membered monocyclic cycloalkyl ring, wherein the 5- or -6-membered monocyclic cycloalkyl ring is as defined herein, and the formed 8- to 10-membered biheterocyclic ring can also be called a 8- to 10-membered heteroaryl cycloalkyl ring. [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] ~ ~ [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document]

[236] In the present disclosure, the above-mentioned various heteroaryl groups may be substituted or unsubstituted; when substituted, the substituents are preferably one or more groups as described in the present application.

[237] As used herein, the term "<com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkoxy" refers to -O-(<com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl), wherein the definition of alkyl is as described above. <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy is preferred, and <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy is more preferred. Non- limiting examples include methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, isobutoxy, pentoxy, etc. Alkoxy may be optionally substituted or non-substituted; and when alkoxy is substituted, the substituents are preferably one or more groups as described in the present application.

[238] As used herein, "deuterated" refers to the substitution of one or more (such as 1, 2, 3, 4 or 5) or all hydrogens in a group with deuterium atoms.

[239] For example, "deuterated <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl" means that one or more (such as 1, 2, 3, 4 or 5) or all hydrogens in alkyl are substituted by deuterium atoms, wherein the definition of alkyl is as described above. Deuterated <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl is preferred, and deuterated <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl is more preferred. For example, deuterated methyl may be mono-deuterated methyl, di-deuterated methyl or per- deuterated methyl.

[240] As used herein, "halo" refers to the substitution of one or more (e.g., 1, 2, 3, 4 or 5) hydrogens in a group with halogen.

[241] For example, "halo <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl" means that alkyl is substituted by one or more (such as 1, 2, 3, 4 or 5) halogens, wherein the definition of alkyl is as described above. Halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl is preferred, and halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl is more preferred. Examples of halo <com:Math><semantics>C1−8<annotation encoding="application / x-tex">C_{1-8}< / annotation>< / semantics>< / com:Math> alkyl include (but are not limited to) monochloromethyl, dichloromethyl, trichloromethyl, monochloroethyl, 1,2- dichloroethyl, trichloroethyl, monobromoethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, monofluoroethyl, difluoroethyl, trifluoroethyl, etc.

[242] For another example, "halo <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkoxy" means that alkoxy is substituted by one or more (such as 1, 2, 3, 4 or 5) halogens, wherein the definition of alkoxy is as described above. Halo <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy is preferred, and halo <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy is more preferred. Examples includes (but not limited to) trifluoromethoxy, trifluoroethoxy, monofluoromethoxy, monofluoroethoxy, difluoromethoxy, difluoroethoxy, etc.

[243] For another example, "halo <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl" means that cycloalkyl is substituted by one or more (such as 1, 2, 3, 4 or 5) halogens, wherein the definition of cycloalkyl is as described above. Halo C<com:Sub>3-6< / com:Sub> cycloalkyl is preferred. Examples includes (but not limited to) trifluorocyclopropyl, monofluorocyclopropyl, monofluorocyclohexyl, difluorocyclopropyl, difluorocyclohexyl, etc. 244 As used herein, the term "hydroxyl" refers to -OH.

[245] As used herein, the term "hydroxymethyl" refers to -CH<com:Sub>2< / com:Sub>OH, and "hydroxyethyl" refers to -CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>OH or -CHOHCH<com:Sub>3< / com:Sub>.

[246] As used herein, the term "cyanomethyl" refers to -CH<com:Sub>2< / com:Sub>CN, "cyanoethyl" refers to - CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>CN or -CHCNCH<com:Sub>3< / com:Sub>.

[247] As used herein, the term "halogen" refers to fluorine, chlorine, bromine or iodine. 248 As used herein, the term "amino" refers to -NH<com:Sub>2< / com:Sub>. |249| As used herein, the term "cyano" refers to -CN.

[250] As used herein, the term "nitro" refers to -NO<com:Sub>2< / com:Sub>.

[251] As used herein, the term "benzyl" refers to -CH<com:Sub>2< / com:Sub>-benzene.

[252] As used herein, the term "oxo" refers to <com:Math><semantics>=0<annotation encoding="application / x-tex">=0< / annotation>< / semantics>< / com:Math>. 253 As used herein, the term "carboxyl" refers to -C(O)OH. |254| As used herein, the term "carboxylate group" refers to -C(O)O(alkyl) or - C(O)O(cycloalkyl). 255 As used herein, the term "acetyl" refers to -COCH<com:Sub>3< / com:Sub>.

[256] As used herein, the wavy line on the group, no matter what form it appears, means that it is the place where it is connected to the rest of the molecule. If there is no wavy line on the group, it means that any position in the group may be connected to other positions of the molecule. 257 "Optional" or "optionally" means that the event or circumstance subsequently described may but need not to occur, and the description includes the occasions where the events or circumstances occur or do not occur. For example, "heterocycloalkyl optionally substituted by alkyl" means that alkyl may but does not have to be present. This description includes the cases where the heterocycloalkyl group is substituted by an alkyl group and the heterocycloalkyl group is not substituted by an alkyl group.

[258] "Substituted" means that one or more hydrogen atoms in the group, preferably up to 5, more preferably 1 to 3 hydrogen atoms, are independently to each other, substituted by a corresponding number of substituents. It goes without saying that the substituents are only in their possible chemical positions, and those skilled in the art can determine (by experiment or theory) possible or impossible substitutions without too much effort. For example, an amino group or a hydroxyl group having free hydrogen may be unstable when combined with a carbon atom having an unsaturated (e.g., olefinic) bond.

[259] Unless otherwise defined, when a group described in the present disclosure is substituted by a substituent, it means that all the same groups appearing in the present disclosure can be substituted by a substituent, which means that the group can be substituted when it exists alone, and it can also be substituted when the group and other groups exist in combination. For example, R is -<com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> monocyclic cycloalkyl, -<com:Math><semantics>C(O)C1−6<annotation encoding="application / x-tex">C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, -<com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl -<com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl or -<com:Math><semantics>S(O)2−1<annotation encoding="application / x-tex">S(O)_{2-1}< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> monocyclic cycloalkyl, wherein the <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl, and <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> monocyclic cycloalkyl are optionally substituted, and the description also includes the case where <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>C6−10<annotation encoding="application / x-tex">C_{6-10}< / annotation>< / semantics>< / com:Math> aryl and <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math> 6 monocyclic cycloalkyl of <com:Math><semantics>−C(O)C1−6<annotation encoding="application / x-tex">-C(O)C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>−C1−4<annotation encoding="application / x-tex">-C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl <com:Math><semantics>−C6−10<annotation encoding="application / x-tex">-C_{6-10}< / annotation>< / semantics>< / com:Math> aryl and <com:Math><semantics>−S(O)2−C3−6<annotation encoding="application / x-tex">-S(O)_2-C_{3-6}< / annotation>< / semantics>< / com:Math> monocyclic cycloalkyl are optionally substituted.

[260] Unless otherwise defined, the "...same or different, and are each independently..." as described in the present disclosure means that when there are more than one identical substituent groups in the general formula, the groups may be the same or different, and are of independent species to each other. For example, L is <com:Math><semantics>(CRL1RL2)s<annotation encoding="application / x-tex">(CR_{L1}R_{L2})_s< / annotation>< / semantics>< / com:Math>; when s is 2, that is, L is <com:Math><semantics>(CRL1RL2)s<annotation encoding="application / x-tex">(CR_{L1}R_{L2})_s< / annotation>< / semantics>< / com:Math>. the two R<com:Sub>L1< / com:Sub> or R<com:Sub>L2< / com:Sub> may be the same or different, and are of independent species to each other; for example, L may be C(CH<com:Sub>3< / com:Sub>)(CN)-C(CH<com:Sub>2< / com:Sub>CH<com:Sub>3< / com:Sub>)(OH), C(CH<com:Sub>3< / com:Sub>)(CN)-C(CH<com:Sub>3< / com:Sub>)(OH) or C(CN)(CH<com:Sub>2< / com:Sub>CH<com:Sub>3< / com:Sub>)- <com:Math><semantics>C(OH)(CH2CH3)<annotation encoding="application / x-tex">C(OH)(CH_2CH_3)< / annotation>< / semantics>< / com:Math>. 261 Unless otherwise defined, the "substituents independently selected from..." as described in the present disclosure means that when more than one hydrogen on the group is substituted by substituents, the types of the substituents may be the same or different, and the selected substituents are of independent species to each other. 262 As used herein, <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> may preferably be <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>; more preferably <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math>; more preferably <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math>. For example, <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkyl may preferably be <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl; more preferably <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkyl; more preferably <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkyl. For example, <com:Math><semantics>C1−10<annotation encoding="application / x-tex">C_{1-10}< / annotation>< / semantics>< / com:Math> alkoxy may preferably be <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkoxy; more preferably <com:Math><semantics>C1−4<annotation encoding="application / x-tex">C_{1-4}< / annotation>< / semantics>< / com:Math> alkoxy; more preferably <com:Math><semantics>C1−3<annotation encoding="application / x-tex">C_{1-3}< / annotation>< / semantics>< / com:Math> alkoxy.

[263] As used herein, <com:Math><semantics>C3−20<annotation encoding="application / x-tex">C_{3-20}< / annotation>< / semantics>< / com:Math> may preferably be <com:Math><semantics>C3−10<annotation encoding="application / x-tex">C_{3-10}< / annotation>< / semantics>< / com:Math>; more preferably <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math>; more preferably <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math>; more preferably <com:Math><semantics>C3−5<annotation encoding="application / x-tex">C_{3-5}< / annotation>< / semantics>< / com:Math>. For example, <com:Math><semantics>C3−20<annotation encoding="application / x-tex">C_{3-20}< / annotation>< / semantics>< / com:Math> cycloalkyl may preferably be <com:Math><semantics>C3−8<annotation encoding="application / x-tex">C_{3-8}< / annotation>< / semantics>< / com:Math> cycloalkyl; more preferably <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl; more preferably <com:Math><semantics>C3−6<annotation encoding="application / x-tex">C_{3-6}< / annotation>< / semantics>< / com:Math> cycloalkyl.

[264] In an embodiment of the present disclosure, in any group, the 3- to 20-membered heterocycloalkyl is 3- to 6-membered heterocycloalkyl, 6- to 10-membered fused heterocycloalkyl, 7- to 11-membered spiroheterocycloalkyl or 7- to 10-membered bridged heterocycloalkyl, wherein, the 3- to 6-membered heterocycloalkyl, 6- to 10-membered fused heterocycloalkyl, 7- to 11- membered spiroheterocycloalkyl, and 7- to 10-membered bridged heterocycloalkyl each independently have 1, 2, or 3 heteroatoms selected from N, O and S as ring atoms.

[265] In an embodiment of the present disclosure, in any group, the C<com:Sub>3-6< / com:Sub> cycloalkyl is selected from: cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[266] In an embodiment of the present disclosure, in any group, the 3- to 6-membered heterocycloalkyl is selected from: aziridine, ethylene oxide, azetidine, oxetane, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, piperidine, piperazine, morpholine, thiomorpholine, thiomorpholine -1,1-dioxide and tetrahydropyran.

[267] In an embodiment of the present disclosure, in any group, the 3- to 6-membered heterocycloalkyl or 3- to 6-membered monocyclic heterocycloalkyl is selected from the following [Image disponible dans le document PDF, Image available in the PDF document]

[268] In an embodiment of the present disclosure, in any group, the 5- or -6-membered monocyclic heteroaryl is selected from: thiophene, N-alkylpyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4- triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine and pyrazine.

[269] In an embodiment of the present disclosure, in any group, the 5- or -6-membered monocyclic heteroaryl is selected from: [Image disponible dans le document PDF, Image available in the PDF document]

[270] In an embodiment of the present disclosure, in any group, the 8- to 10-membered bicyclic heteroaryl is selected from: benzoxazole, benzisoxazole, benzimidazole, benzothiazole, benzisothiazole, benzotriazole, benzofuran, benzothiophene, indole, indazole, isoindole, quinoline, isoquinoline, quinazoline, quinoxaline, cinnoline, pyridopyrimidine and naphthyridine.

[271] "Pharmaceutical composition" means a mixture containing one or more of the compounds described herein or physiologically / pharmaceutically acceptable salts or prodrugs thereof, and other chemical components, as well as other components such as physiological / pharmaceutically acceptable carriers and excipients. The purpose of the pharmaceutical composition is to promote the administration to the organism, facilitate the absorption of the active ingredients and then exert the biological activity. 272 The "pharmaceutically acceptable salt" includes pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts.

[273] "Pharmaceutically acceptable acid addition salt" refers to a salt formed with an inorganic acid or an organic acid that can retain the biological effectiveness of the free base without other side effects.

[274] "Pharmaceutically acceptable base addition salts" include, but are not limited to, salts of inorganic bases such as sodium, potassium, calcium and magnesium salts; and include, but not limited to salts of organic bases, such as ammonium, triethylamine, lysine and arginine salts.

[275] The "solvate" mentioned in the present disclosure refers to a complex formed by the compound of the present disclosure and a solvent. They are obtained either by reacting in a solvent or precipitating or crystallizing out of the solvent. For example, a complex formed from the compound with water is called a "hydrate". The so...

Claims

1. A dihydronaphthyridinone compound, or a pharmaceutically acceptable salt, a stereoisomer, or a solvate thereof characterized in that the compound has a structure represented by formula (I): [Image disponible dans le document PDF, Image available in the PDF document] (I) wherein, R 1 R_1 and R 2 R_2 are each independently hydrogen, halogen, substituted or unsubstituted C 1 − 6 C_{1-6} alkyl, substituted or unsubstituted C 1-6 alkoxy or substituted or unsubstituted NR a0 R b0 , wherein R a0 and R b0 are each independently hydrogen or C 1-3 alkyl; or R a0 and R b0 form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl; the "substituted" in R 1 R_1 and R 2 R_2 means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; the definition for R 3 R_3 , R 4 R_4 , R 5 R_5 and R 6 R_6 are selected from one of the following groups: (i) R 3 , R 4 , R 5 and R 6 are each independently hydrogen, halogen, substituted or unsubstituted C 1 − 6 C_{1-6} alkyl, or substituted or unsubstituted C 3 − 8 C_{3-8} cycloalkyl; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; (ii) R 3 and R 4 form together with the carbon atom adjacent thereto a substituted or unsubstituted C 3-8 cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; R 5 and R 6 are each independently hydrogen, halogen, substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 3-8 cycloalkyl; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; (iii) R 3 and R 4 are each independently hydrogen, halogen, substituted or unsubstituted C 1-6 alkyl, or substituted or unsubstituted C 3 − 8 C_{3-8} cycloalkyl; R 5 R_5 and R 6 R_6 form together with the carbon atom adjacent thereto a substituted or unsubstituted C 3 − 8 C_{3-8} cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; (iv) R 4 and R 5 form together with the carbon atom adjacent thereto a substituted or unsubstituted C 3-8 cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; R 3 and R 6 are each independently hydrogen, halogen, substituted or unsubstituted C 1 − 6 C_{1-6} alkyl, or substituted or unsubstituted C 3 − 8 C_{3-8} cycloalkyl; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; B is-L-R 0 , wherein, R 0 R_0 is substituted or unsubstituted C 6 − 14 C_{6-14} aryl, substituted or unsubstituted 5- to 14-membered heteroaryl or substituted or unsubstituted 5- to 14-membered heterocycloalkyl; the "substituted" in R 0 means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; L is a bond, − ( C R 11 R 12 ) t 1 − ( C R 21 R 22 ) t 2 − ( C R 31 R 32 ) t 3 − ( C R 41 R 42 ) t 4 − ( O ) t 5 -(CR_{11}R_{12})_{t1}-(CR_{21}R_{22})_{t2}-(CR_{31}R_{32})_{t3}-(CR_{41}R_{42})_{t4}-(O)_{t5} or − ( C R 13 R 14 ) t 1 -(CR_{13}R_{14})_{t1} ( C R 23 R 24 ) t 2 (CR_{23}R_{24})_{t2} - ( N R 33 ) t 3 (NR_{33})_{t3} - ( C R 43 R 44 ) t 4 (CR_{43}R_{44})_{t4} - ( O ) t 5 (O)_{t5} -, wherein t1, t2, t3, t4 and t5 are each independently 0 or 1; the definition for R 11 , R 12 , R 21 , R 22 , R 31 , R 32 , R 41 and R 42 are selected from one of the following groups: (a2) R 11 , R 12 , R 41 and R 42 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; R 21 , R 22 , R 31 and R 32 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; (b2) R 11 , R 12 , R 41 and R 42 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; R 21 R_{21} and R 22 R_{22} form together with the carbon atom adjacent thereto a substituted or unsubstituted C 3-8 cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; R 31 and R 32 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; (c2) R 11 , R 12 , R 41 and R 42 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1-3 alkyl; R 21 and R 22 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; R 31 R_{31} and R 32 R_{32} form together with the carbon atom adjacent thereto a substituted or unsubstituted C 3-8 cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; (d2) R 11 , R 12 , R 41 and R 42 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; R 22 and R 32 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; R 21 R_{21} and R 31 R_{31} form together with the atom adjacent thereto a substituted or unsubstituted C 3 − 8 C_{3-8} cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; (e2) R 12 , R 41 and R 42 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; R 21 , R 22 and R 32 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; R 11 R_{11} and R 31 R_{31} form together with the atom adjacent thereto a substituted or unsubstituted C 3 − 8 C_{3-8} cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; the definition for R 13 , R 14 , R 23 , R 24 , R 33 , R 43 and R 44 are selected from one of the following groups: (a3) R 13 , R 14 , R 23 , R 24 , R 43 and R 44 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1-3 alkyl; R 33 R_{33} is hydrogen, deuterium, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; (b3) R 13 , R 14 , R 43 and R 44 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; R 23 R_{23} and R 24 R_{24} form together with the carbon atom adjacent thereto a substituted or unsubstituted C 3-8 cycloalkyl ring or a substituted or unsubstituted 3- to 6-membered heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; R 33 R_{33} is hydrogen, deuterium, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; (c3) R 13 , R 14 , R 23 , R 43 and R 44 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; R 24 and R 33 form together with the atom adjacent thereto a substituted or unsubstituted 3- to 6- membered nitrogen-containing heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; (d3) R 13 , R 23 , R 24 , R 43 and R 44 are each independently hydrogen, deuterium, halogen, hydroxyl, hydroxymethyl, hydroxyethyl or C 1 − 3 C_{1-3} alkyl; R 14 and R 33 form together with the atom adjacent thereto a substituted or unsubstituted 3- to 6- membered nitrogen-containing heterocycloalkyl ring; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; A is (i) unsubstituted 5- or 6-membered monocyclic heteroaryl; (ii) substituted or unsubstituted 8- to 10-membered bicyclic heteroaryl, wherein the 8- to 10-membered bicyclic heteroaryl is formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; (iii) substituted or unsubstituted 9- or 10-membered bicyclic heteroaryl; the 9- or 10-membered bicyclic heteroaryl is formed by fusing a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring; wherein the 5- or 6-membered monocyclic heteroaryl ring is selected from: [Image disponible dans le document PDF, Image available in the PDF document] wherein the attached two carbon atoms represented by " " are adjacent pairs of carbon atoms shared when fused with other rings; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; (iv) substituted or unsubstituted 8- to 10-membered bicyclic heteroaryl; the 8- to 10-membered bicyclic heteroaryl is formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; or (v) substituted or unsubstituted benzothiazole, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S'; in the above groups, the substituents from group S are selected from deuterium, halogen, nitro, oxo, -C 1-6 alkyl, -halo C 1-6 alkyl, -deuterated C 1-6 alkyl, -S-C 1-6 alkyl, -S-halo C 1-6 alkyl, -(CR a1 R b1 ) u - cyano, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -hydroxyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - C 1 − 6 C_{1-6} alkoxy, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -halo C 1 − 6 C_{1-6} alkoxy, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - deuterated C 1 − 6 C_{1-6} alkoxy, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -halo C 1 − 6 C_{1-6} alkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -deuterated C 1 − 6 C_{1-6} alkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - 3- to 6-membered heterocycloalkyl, − ( C R a 1 R b 1 ) u − C 3 − 8 -(CR_{a1}R_{b1})_u-C_{3-8} cycloalkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -phenyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - 5- or 6-membered monocyclic heteroaryl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -O- − ( C R a 2 R b 2 ) v -(CR_{a2}R_{b2})_v -halo C 1 − 6 C_{1-6} alkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -O- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v - C 3 − 8 C_{3-8} cycloalkyl, - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u -O- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -3- to 6-membered heterocycloalkyl, - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u -O- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -phenyl, - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u -O- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -5- or 6-membered monocyclic heteroaryl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -S- − ( C R a 2 R b 2 ) v -(CR_{a2}R_{b2})_v -phenyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -SO 2 - − ( C R a 2 R b 2 ) v -(CR_{a2}R_{b2})_v -phenyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -O- C ( O ) N R a 0 R b 0 C(O)NR_{a0}R_{b0} , − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - O − ( C R a 2 R b 2 ) v O-(CR_{a2}R_{b2})_v - C 1 − 6 C_{1-6} alkoxy, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - O − ( C R a 2 R b 2 ) v O-(CR_{a2}R_{b2})_v -hydroxyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - O − ( C R a 2 R b 2 ) v O-(CR_{a2}R_{b2})_v -hydroxyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - O − ( C R a 2 R O-(CR_{a2}R ( C R a 1 R b 1 ) u − S O 2 C 1 − 6 (CR_{a1}R_{b1})_{u}-SO_{2}C_{1-6} alkyl, − ( C R a 1 R b 1 ) u − S O 2 N R a 0 R b 0 -(CR_{a1}R_{b1})_{u}-SO_{2}NR_{a0}R_{b0} , − ( C R a 1 R b 1 ) u − C ( O ) N R a 0 R b 0 -(CR_{a1}R_{b1})_{u}-C(O)NR_{a0}R_{b0} , − ( C R a 1 R b 1 ) u − C ( O ) N R a 0 R b 0 -(CR_{a1}R_{b1})_{u}-C(O)NR_{a0}R_{b0} C ( O ) C(O) phenyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u − C ( O ) C 1 − 6 -C(O)C_{1-6} alkyl, − C ( O ) O C 1 − 6 -C(O)OC_{1-6} alkyl, − C ( O ) − ( C R a 2 R b 2 ) v -C(O)-(CR_{a2}R_{b2})_v hydroxyl, − C ( O ) -C(O) ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u - N R a 0 R b 0 NR_{a0}R_{b0} , - N R a 0 C ( O ) NR_{a0}C(O) - C 1 − 6 C_{1-6} alkyl, - N R a 0 C ( O ) NR_{a0}C(O) -deuterated C 1 − 6 C_{1-6} alkyl, - N R a 0 C ( O ) NR_{a0}C(O) - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u -hydroxyl, − N R a 0 C ( O ) -NR_{a0}C(O) - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u - O O - ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v - C ( O ) C 1 − 6 C(O)C_{1-6} alkyl, − N R a 0 C ( O ) -NR_{a0}C(O) - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u - O − ( C R a 2 R b 2 ) v O-(CR_{a2}R_{b2})_v -phenyl, − N R a 0 C ( O ) − C 3 − 8 -NR_{a0}C(O)-C_{3-8} cycloalkyl, − N R a 0 C ( O ) − ( C R a 1 R b 1 ) u -NR_{a0}C(O)-(CR_{a1}R_{b1})_u - N R a 0 R b 0 NR_{a0}R_{b0} , and − N R a 0 C ( O ) -NR_{a0}C(O) - halo C 1 − 6 C_{1-6} alkyl, wherein the C 3 − 8 C_{3-8} cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, C 1-3 alkyl, halo C 1 − 3 C_{1-3} alkyl, C 1 − 3 C_{1-3} alkoxy, halo C 1 − 3 C_{1-3} alkoxy, C 3 − 6 C_{3-6} cycloalkyl and halo C 3 − 6 C_{3-6} cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R a0 and R b0 are each independently hydrogen or C 1-3 alkyl; or R a0 and R b0 form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen- containing heterocycloalkyl, wherein the 3- to 8-membered nitrogen-containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or C 1 − 3 C_{1-3} alkyl; R a 1 R_{a1} , R b 1 R_{b1} , R a 2 R_{a2} and R b 2 R_{b2} are the same or different, and are each independently hydrogen, hydroxyl, C 1-3 alkyl or halo C 1-3 alkyl; in the above groups, the substituents from group S' are selected from deuterium, halogen, nitro, oxo, − C 1 − 6 -C_{1-6} alkyl, -halo C 1 − 6 C_{1-6} alkyl, -deuterated C 1 − 6 C_{1-6} alkyl, − S − C 1 − 6 -S-C_{1-6} alkyl, − S -S -halo C 1 − 6 C_{1-6} alkyl, - ( C R a 1 ′ R b 1 ′ ) u ′ (CR_{a1}'R_{b1}')_{u}' -cyano, − ( C R a 1 ′ R b 1 ′ ) u ′ -(CR_{a1}'R_{b1}')_{u}' -hydroxyl, − ( C R a 1 ′ R b 1 ′ ) u ′ -(CR_{a1}'R_{b1}')_{u}' - − C 1 − 6 -C_{1-6} alkoxy, − ( C R a 1 ′ R b 1 ′ ) u ′ -(CR_{a1}'R_{b1}')_{u}' -halo C 1 − 6 C_{1-6} alkoxy, -(CR a1 'R b1 ') u '-halo C 1-6 alkyl, -(CR a1 'R b1 ') u '-3- to 6-membered heterocycloalkyl, - ( C R a 1 ′ R b 1 ′ ) u ′ − C 3 − 8 (CR_{a1}'R_{b1}')_u'-C_{3-8} cycloalkyl, − ( C R a 1 ′ R b 1 ′ ) u ′ -(CR_{a1}'R_{b1}')_u' -phenyl, − ( C R a 1 ′ R b 1 ′ ) u ′ -(CR_{a1}'R_{b1}')_u' -5- or 6-membered monocyclic heteroaryl, − ( C R a 1 ′ R b 1 ′ ) u ′ − O − ( C R a 2 ′ R b 2 ′ ) v ′ − h a l o -(CR_{a1}'R_{b1}')_u'-O-(CR_{a2}'R_{b2}')_v'-halo C 1 − 6 C_{1-6} alkyl, − ( C R a 1 ′ R b 1 ′ ) u ′ − O − ( C R a 2 ′ R b 2 ′ ) v ′ − C 3 − 8 -(CR_{a1}'R_{b1}')_u'-O-(CR_{a2}'R_{b2}')_v'-C_{3-8} cycloalkyl, -(CR a1 'R b1 ') u '-O-(CR a2 'R b2 ') v '-3- to 6-membered heterocycloalkyl, -(CR a1 'R b1 ') u '-O- (CR a2 'R b2 ') v -phenyl, -(CR a1 'R b1 ') u '-O-(CR a2 'R b2 ') v '-5- or 6-membered monocyclic heteroaryl, - ( C R a 1 ′ R b 1 ′ ) u (CR_{a1}'R_{b1}')_{u} -S- ( C R a 2 ′ R b 2 ′ ) v ′ (CR_{a2}'R_{b2}')_{v}' -phenyl, − ( C R a 1 ′ R b 1 ′ ) u ′ -(CR_{a1}'R_{b1}')_{u}' -SO 2 - ( C R a 2 ′ R b 2 ′ ) v ′ (CR_{a2}'R_{b2}')_{v}' -phenyl, − ( C R a 1 ′ R b 1 ′ ) u ′ -(CR_{a1}'R_{b1}')_{u}' -O- C ( O ) N R a 0 ′ R b 0 ′ C(O)NR_{a0}'R_{b0}' , − ( C R a 1 ′ R b 1 ′ ) u ′ − O − ( C R a 2 ′ R b 2 ′ ) v ′ − C 1 − 6 -(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-C_{1-6} alkoxy, − ( C R a 1 ′ R b 1 ′ ) u ′ − O − ( C R a 2 ′ R b 2 ′ ) v ′ − C 1 − 6 -(CR_{a1}'R_{b1}')_{u}'-O-(CR_{a2}'R_{b2}')_{v}'-C_{1-6} hydroxyl, − ( C R a 1 ′ R b 1 ′ ) u ′ − S O 2 C 1 − 6 -(CR_{a1}'R_{b1}')_{u}'-SO_{2}C_{1-6} alkyl, − ( C R a 1 ′ R b 1 ′ ) u ′ − S O 2 N R a 0 ′ R b 0 ′ -(CR_{a1}'R_{b1}')_{u}'-SO_{2}NR_{a0}'R_{b0}' , − ( C R a 1 ′ R b 1 ′ ) u ′ -(CR_{a1}'R_{b1}')_{u}' C ( O ) N R a 0 ′ R b 0 ′ C(O)NR_{a0}'R_{b0}' , − ( C R a 1 ′ R b 1 ′ ) u ′ − C ( O ) -(CR_{a1}'R_{b1}')_{u}'-C(O) phenyl, − ( C R a 1 ′ R b 1 ′ ) u ′ − C ( O ) C 1 − 6 -(CR_{a1}'R_{b1}')_{u}'-C(O)C_{1-6} alkyl, − C ( O ) O C 1 − 6 -C(O)OC_{1-6} alkyl, and C(O)-(CR a2 'R b2 ') v '-hydroxyl, wherein the C 3-8 cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, C 1-3 alkyl, halo C 1-3 alkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 3-6 cycloalkyl and halo C 3-6 cycloalkyl; u' and v' are each independently 0, 1, 2, 3 or 4; R a0 ' and R b0 ' are each independently hydrogen or C 1-3 alkyl; or R a0 ' and R b0 ' form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl, wherein the 3- to 8-membered nitrogen- containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or C 1-3 alkyl; R a1 ', R b1 ', R a 2 R_{a2} ' and R b 2 R_{b2} ' are the same or different, and are each independently hydrogen, hydroxyl, C 1 − 3 C_{1-3} alkyl or halo C 1 − 3 C_{1-3} alkyl.

2. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 1, wherein A is unsubstituted 5- or 6-membered monocyclic heteroaryl.

3. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 1, wherein A is substituted or unsubstituted 8- to 10-membered bicyclic heteroaryl, the 8- to 10-membered bicyclic heteroaryl is formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heteroaryl ring, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; the group S are as defined in claim 1.

4. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 1, wherein A is substituted or unsubstituted 9- or 10-membered bicyclic heteroaryl; the 9- or 10-membered bicyclic heteroaryl is formed by fusing a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring; wherein the 5- or 6-membered monocyclic heteroaryl ring is selected from: [Image disponible dans le document PDF, Image available in the PDF document] wherein the attached two carbon atoms represented by " ---- " are adjacent pairs of carbon atoms shared when fused with other rings; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; the group S are as defined in claim 1.

5. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 1, wherein A is substituted or unsubstituted 8- to 10-membered bicyclic heteroaryl; the 8- to 10-membered bicyclic heteroaryl is formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S; the group S are as defined in claim 1.

6. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 1, wherein A is substituted or unsubstituted benzothiazole, wherein the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S'; the group S' are as defined in claim 1.

7. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 3 characterized in that with regard to A, the 8- to 10-membered bicyclic heteroaryl formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6- membered monocyclic heteroaryl ring has a structure represented by formula (A1): [Image disponible dans le document PDF, Image available in the PDF document] , wherein Z 1 is N or CR Z1 ; Z 2 is NR Z2 or O; Z 3 is N or CR Z3 ; Z 4 is N or CR Z4 ; Z 5 is N or CR Z5 ; Z 6 is N or CR Z6 ; Z 3 , Z 4 , Z 5 and Z 6 are not N at the same time; and at least one of Z 3 , Z 4 , Z 5 and Z 6 is N; R Z0 , R Z1 , R Z2 , R Z3 , R Z4 , R Z5 and R Z6 are each independently hydrogen or the substituent from group S.

8. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 3 characterized in that with regard to A, the 8- to 10-membered bicyclic heteroaryl formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6- membered monocyclic heteroaryl ring has a structure represented by formula (A2): [Image disponible dans le document PDF, Image available in the PDF document] , wherein Y 1 is N or CR Y1 ; Y 2 is N or CR Y2 ; Y 3 is N or CR Y3 ; Y 4 is N or CR Y4 ; Y 5 is N or CR Y5 ; Y 6 is N or CR Y6 ; Y 7 is N or CR Y7 ; Y 3 , Y 4 , Y 5 , Y 6 and Y 7 are not N at the same time; and at least one of Y 1 , Y 2 , Y 3 , Y 4 , Y 5 , Y 6 and Y 7 is N; R Y0 , R Y1 , R Y2 , R Y3 , R Y4 , R Y5 , R Y6 and R Y7 are each independently hydrogen or the substituent from group S.

9. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 3 characterized in that with regard to A, the 8- to 10-membered bicyclic heteroaryl formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6- membered monocyclic heteroaryl ring has a structure represented by formula (A3): [Image disponible dans le document PDF, Image available in the PDF document] , wherein U 1 is N or CR U1 ; U 2 is N or CR U2 ; U 3 is N or CR U3 ; U 4 is N or CR U4 ; U 5 is N or CR U5 ; U 6 is N or CR U6 ; U 7 is N or CR U7 ; U 8 is N or CR U8 ; U 4 , U 5 , U 6 , U 7 and U 8 are not N at the same time; and at least one of U 1 , U 2 , U 3 , U 4 , U 5 , U 6 , U 7 and U 8 is N; R U1 , R U2 , R U3 , R U4 , R U5 , R U6 , R U7 and R U8 are each independently hydrogen or the substituent from group S.

10. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 4 characterized in that the 9- or 10-membered bicyclic heteroaryl said in A formed by fusing a benzene ring with a 5- or 6-membered monocyclic heteroaryl ring has a structure represented by formula (A4): [Image disponible dans le document PDF, Image available in the PDF document] wherein W 1 is N or CR W1 ; W 2 is NR W2 or O; n is 1, 2 or 3; R W0 , R W1 , R W2 and R W3 are each independently hydrogen or the substituent from group S.

11. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 5 characterized in that the 8- to 10-membered bicyclic heteroaryl said in A formed by fusing a 5- or 6-membered monocyclic heteroaryl ring with a 5- or 6-membered monocyclic heterocycloalkyl ring has a structure represented by formula (A5): [Image disponible dans le document PDF, Image available in the PDF document] , wherein G 1 is N or CR G1 ; G 2 is N or CR G2 ; G 3 is N or CR G3 ; G 4 is NR G4a , O or CR G4b R G4c ; G 5 is NR G5a , O or CR G5b R G5c ; G 6 is NR G6a , O or CR G6b R G6c ; G 7 is NR G7a , O or CR G7b R G7c ; at least one of G 3 , G 4 , G 5 , G 6 and G 7 is N; and the ring part of -G 3 -G 4 -G 5 -G 6 -G 7 - does not comprise -O-O-, -O- N- or-N-N-; R G0 , R G1 , R G2 , R G3 , R G4a , R G4b , R G4c , R G5a , R G5b , R G5c , R G6a , R G6b , R G6c , R G7a , R G7b and R G7c are each independently hydrogen or the substituent from group S.

12. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 1 characterized in that the compound has a structure represented by formula (I-1): [Image disponible dans le document PDF, Image available in the PDF document] ( I − 1 ) (I-1) wherein, i and j are each independently 0, 1 or 2; and i and j are not 0 at the same time; R 7 is hydrogen, deuterium, halogen, nitro, oxo, -C 1-6 alkyl, -halo C 1-6 alkyl, -deuterated C 1-6 alkyl, -S-C 1-6 alkyl, -S- halo C 1 − 6 C_{1-6} alkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -cyano, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -hydroxyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - − C 1 − 6 -C_{1-6} alkoxy, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -halo C 1 − 6 C_{1-6} alkoxy, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -halo C 1 − 6 C_{1-6} alkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -deuterated C 1 − 6 C_{1-6} alkoxy, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -deuterated C 1 − 6 C_{1-6} alkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -3- to 6-membered heterocycloalkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - C 3 − 8 C_{3-8} cycloalkyl, - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u -phenyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -5- or 6-membered monocyclic heteroaryl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -O- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -halo C 1 − 6 C_{1-6} alkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -O- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -C 3-8 cycloalkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -O- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -3- to 6-membered heterocycloalkyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -O- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -phenyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -O- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -5- or 6-membered monocyclic heteroaryl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -S- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -phenyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -SO 2 - ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -phenyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -O-C(O)NR a0 R b0 , − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u -O-(CR a2 R b2 ) v -C 1-6 alkoxy, - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_{u} -O- ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_{v} -hydroxyl, - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_{u} -SO 2 C 1-6 alkyl, - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_{u} -SO 2 NR a0 R b0 , - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u - C ( O ) N R a 0 R b 0 C(O)NR_{a0}R_{b0} , - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u - C ( O ) C(O) phenyl, - ( C R a 1 R b 1 ) u (CR_{a1}R_{b1})_u - C ( O ) C 1 − 6 C(O)C_{1-6} alkyl, - C ( O ) O C 1 − 6 C(O)OC_{1-6} alkyl, - C ( O ) O C 1 − 6 C(O)OC_{1-6} alkyl, - C ( O ) O C 1 − 6 C(O)OC_{1-6} alkyl, - C ( O ) O C 1 − 6 C(O)OC_{1-6} alkyl, -<Formule mathématique disponible dans le document PDF, Math available in the PDF document>C(O)OC_{1 C ( O ) − ( C R a 2 R b 2 ) v − h y d r o x y l , − ( C R a 1 R b 1 ) u − N R a 0 R b 0 , − N R a 0 C ( O ) − C 1 − 6 C(O)-(CR_{a2}R_{b2})_v-hydroxyl, -(CR_{a1}R_{b1})_u-NR_{a0}R_{b0}, -NR_{a0}C(O)-C_{1-6} alkyl, − N R a 0 C ( O ) -NR_{a0}C(O) -deuterated C 1 − 6 C_{1-6} alkyl, − N R a 0 C ( O ) − ( C R a 1 R b 1 ) u − h y d r o x y l -NR_{a0}C(O)-(CR_{a1}R_{b1})_u-hydroxyl , − N R a 0 C ( O ) − ( C R a 1 R b 1 ) u − O − ( C R a 2 R b 2 ) v − C ( O ) C 1 − 6 -NR_{a0}C(O)-(CR_{a1}R_{b1})_u-O-(CR_{a2}R_{b2})_v-C(O)C_{1-6} alkyl, − R a 0 C ( O ) − ( C R a 1 R b 1 ) u − O − ( C R a 2 R b 2 ) v − C ( O ) C 1 − 6 -R_{a0}C(O)-(CR_{a1}R_{b1})_u-O-(CR_{a2}R_{b2})_v-C(O)C_{1-6} alkyl, − R a 0 C ( O ) − ( C R a 1 R b 1 ) -R_{a0}C(O)-(CR_{a1}R_{b1}) N R a 0 C ( O ) − ( C R a 1 R b 1 ) u − O − ( C R a 2 R b 2 ) v − p h e n y l NR_{a0}C(O)-(CR_{a1}R_{b1})_{u}-O-(CR_{a2}R_{b2})_{v}-phenyl , − N R a 0 C ( O ) − C 3 − 8 -NR_{a0}C(O)-C_{3-8} cycloalkyl, − N R a 0 C ( O ) − ( C R a 1 R b 1 ) u − C 3 − 8 -NR_{a0}C(O)-(CR_{a1}R_{b1})_{u}-C_{3-8} N R a 0 R b 0 NR_{a0}R_{b0} , or − N R a 0 C ( O ) -NR_{a0}C(O) -halo C 1 − 6 C_{1-6} alkyl, wherein the C 3 − 8 C_{3-8} cycloalkyl, 3- to 6-membered heterocycloalkyl, phenyl, and 5- or 6-membered monocyclic heteroaryl are optionally substituted with 1, 2 or 3 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, C 1-3 alkyl, halo C 1-3 alkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 3-6 cycloalkyl and halo C 3-6 cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R a0 and R b0 are each independently hydrogen or C 1 − 3 C_{1-3} alkyl; or R a 0 R_{a0} and R b 0 R_{b0} form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl, wherein the 3- to 8-membered nitrogen-containing heterocycloalkyl is optionally substituted with 1, 2 or 3 halogens or C 1 − 3 C_{1-3} alkyl; R a1 , R b1 , R a2 and R b2 are the same or different, and are each independently hydrogen, hydroxyl, C 1 - 3 alkyl or halo C 1 − 3 C_{1-3} alkyl; R 8 R_8 is hydrogen, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - S O 2 SO_2 - ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -phenyl, − ( C R a 1 R b 1 ) u -(CR_{a1}R_{b1})_u - S O 2 C 1 − 6 SO_2C_{1-6} alkyl, − ( C R a 1 R b 1 ) u − S O 2 N R a 0 R b 0 -(CR_{a1}R_{b1})_u-SO_2NR_{a0}R_{b0} , − ( C R a 1 R b 1 ) u − C ( O ) N R a 0 R b 0 -(CR_{a1}R_{b1})_u-C(O)NR_{a0}R_{b0} , − ( C R a 1 R b 1 ) u − C ( O ) -(CR_{a1}R_{b1})_u-C(O) C ( O ) C 1 − 6 C(O)C_{1-6} alkyl, or- C ( O ) C(O) - ( C R a 2 R b 2 ) v (CR_{a2}R_{b2})_v -hydroxyl, wherein the phenyl and C 1 − 6 C_{1-6} alkyl are optionally substituted with 1, 2, 3 or 4 substituents selected from hydroxyl, hydroxymethyl, hydroxyethyl, halogen, cyano, cyanomethyl, cyanoethyl, C 1 − 3 C_{1-3} alkyl, halo C 1 − 3 C_{1-3} alkyl, C 1 − 3 C_{1-3} alkoxy, halo C 1 − 3 C_{1-3} alkoxy, C 3-6 cycloalkyl and halo C 3-6 cycloalkyl; u and v are each independently 0, 1, 2, 3 or 4; R a0 and R b0 are each independently hydrogen or C 1-3 alkyl; or R a0 and R b0 form together with the nitrogen atom adjacent thereto a 3- to 8-membered nitrogen-containing heterocycloalkyl; R a1 , R b1 , R a2 and R b2 are the same or different, and are each independently hydrogen, hydroxyl, C 1 − 3 C_{1-3} alkyl or halo C 1 − 3 C_{1-3} alkyl; the other groups are as defined in claim 1.

13. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 12 characterized in that the compound of formula (I-1) has a structure represented by formula (I-1-a), formula (I-1-b), formula (I-1-c) or formula (I-1-d): [Image disponible dans le document PDF, Image available in the PDF document] , wherein, each group is as defined in claim 12.

14. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 1 characterized in that A has a structure selected from: [Image disponible dans le document PDF, Image available in the PDF document] WSLEGAL\092120\00005\39745792v1 [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] J Wherein R W01 , R W2 , R W02 , R W03 , R Y01 , R Y02 , R U8 , R U1 and R G0 are each independently hydrogen or the substituent from group S; R E1 is hydrogen; R E0 is hydrogen or the substituent from group S'; m is 1, 2, 3 or 4.

15. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-11 and 14 characterized in that the C 6 − 14 C_{6-14} aryl said in R 0 R_0 is phenyl, naphthyl, or is a 9- or 10-membered aromatic fused bicyclic ring formed by fusing phenyl with a non-aromatic ring; the non-aromatic ring is 3- to 6-membered saturated or partially unsaturated monocyclic heterocycloalkyl or 3- to 6-membered saturated or partially unsaturated monocyclic cycloalkyl, wherein the 3- to 6-membered saturated or partially unsaturated monocyclic heterocycloalkyl is selected from aziridine, ethylene oxide, azetidine, azetidine-2-one, oxetane, oxetane-2-one, oxazolidine, pyrrolidine-2-one, pyrrolidine-2,5-dione, 1,3-dioxolane, dihydrofuran- 2(3H)-one, dihydrofuran-2,5-dione, piperidine-2-one, piperidine-2,6-dione, tetrahydro-2H-pyran- 2-one, imidazolidine, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, 1,3-dioxolane-2-one, oxazolidine-2-one, imidazolidine-2-one, piperidine, piperazine, piperazine-2-one, morpholine, morpholine-3-one, morpholine-2-one, thiomorpholine-3-one 1,1-dioxide, thiomorpholine, thiomorpholine-1,1-dioxide, tetrahydropyran, 1,2-dihydroazetidine, 1,2-dihydrooxetadiene, 2,5- dihydro-1H-pyrrole, 2,5-dihydrofuran, 2,3-dihydrofuran, 2,3-dihydro-1H-pyrrole, 3,4-dihydro-2H- pyran, 1,2,3,4-tetrahydropyridine, 3,6-dihydro-2H-pyran, 1,2,3,6-tetrahydropyridine, 1,3- oxazinane, hexahydropyrimidine, 1,4-dioxane, tetrahydropyrimidine-2(1H)-one, 1,4-dioxane-2-one, and 5,6-dihydro-2H-pyran-2-one; the 3- to 6-membered saturated or partially unsaturated monocyclic cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane-1,3-dione; the phenyl, naphthyl, or 9- or 10-membered aromatic fused bicyclic ring is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

16. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-11 and 14-15 characterized in that the 5- to 14-membered heteroaryl said in R 0 is 5- or 6-membered monocyclic heteroaryl, wherein the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, N-alkyl pyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4- triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine; the 5- or 6-membered monocyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

17. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-11 and 14-15 characterized in that the 5- to 14-membered heteroaryl said in R 0 is 9- or 10-membered bicyclic heteroaryl formed by fusing phenyl with 5- or 6-membered monocyclic heteroaryl, wherein the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, N-alkyl pyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine; the 9- or 10-membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

18. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-11 and 14-15 characterized in that the 5- to 14-membered heteroaryl said in R 0 is 8- to 10-membered bicyclic heteroaryl formed by fusing 5- or 6-membered monocyclic heteroaryl with 5- or 6-membered monocyclic heteroaryl, wherein the 5- or 6- membered monocyclic heteroaryl is selected from thiophene, N-alkyl pyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5- triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5- oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine; the 8- to 10- membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

19. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-11 and 14-15 characterized in that the 5- to 14-membered heteroaryl said in R 0 is 8- to 10-membered bicyclic heteroaryl formed by fusing 5- or 6-membered monocyclic heteroaryl with a non-aromatic ring, wherein the non-aromatic ring is 3- to 6-membered saturated or partially unsaturated monocyclic heterocycloalkyl or 3- to 6-membered saturated or partially unsaturated monocyclic cycloalkyl; the 5- or 6-membered monocyclic heteroaryl is selected from thiophene, N-alkyl pyrrolidone, furan, thiazole, isothiazole, imidazole, oxazole, pyrrole, pyrazole, triazole, 1,2,3-triazole, 1,2,4-triazole, 1,2,5-triazole, 1,3,4-triazole, tetrazole, isoxazole, oxadiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,5-oxadiazole, 1,3,4-oxadiazole, thiadiazole, pyridine, pyridazine, pyrimidine or pyrazine; the 3- to 6-membered saturated or partially unsaturated monocyclic heterocycloalkyl is selected from aziridine, ethylene oxide, azetidine, azetidine-2-one, oxetane, oxetane-2-one, oxazolidine, pyrrolidine-2-one, pyrrolidine-2,5-dione, 1,3-dioxolane, dihydrofuran-2(3H)-one, dihydrofuran-2,5-dione, piperidine-2-one, piperidine-2,6- dione, tetrahydro-2H-pyran-2-one, imidazolidine, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, 1,3-dioxolane-2-one, oxazolidine-2-one, imidazolidine-2-one, piperidine, piperazine, piperazine-2-one, morpholine, morpholine-3-one, morpholine-2-one, thiomorpholine-3- one 1,1-dioxide, thiomorpholine, thiomorpholine-1,1-dioxide, tetrahydropyran, 1,2- dihydroazetidine, 1,2-dihydrooxetadiene, 2,5-dihydro-1H-pyrrole, 2,5-dihydrofuran, 2,3- dihydrofuran, 2,3-dihydro-1H-pyrrole, 3,4-dihydro-2H-pyran, 1,2,3,4-tetrahydropyridine, 3,6- dihydro-2H-pyran, 1,2,3,6-tetrahydropyridine, 1,3-oxazinane, hexahydropyrimidine, 1,4-dioxane, tetrahydropyrimidine-2(1H)-one, 1,4-dioxane-2-one, and 5,6-dihydro-2H-pyran-2-one; the 3- to 6- membered saturated or partially unsaturated monocyclic cycloalkyl is selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cyclohexadienyl, cyclobutanone, cyclobutane-1,2-dione, cyclopentanone, cyclopentane-1,3-dione, cyclohexanone, and cyclohexane- 1,3-dione; the 8- to 10-membered bicyclic heteroaryl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

20. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-11, 14-19 characterized in that the 5- to 14-membered heterocycloalkyl said in R 0 is 5- to 6-membered heterocycloalkyl, wherein the 5- to 6-membered heterocycloalkyl is selected from oxazolidine, pyrrolidine-2-one, pyrrolidine-2,5-dione, 1,3- dioxolane, dihydrofuran-2(3H)-one, dihydrofuran-2,5-dione, piperidine-2-one, piperidine-2,6- dione, tetrahydro-2H-pyran-2-one, imidazolidine, tetrahydrofuran, tetrahydrothiophene, tetrahydropyrrole, 1,3-dioxolane-2-one, oxazolidine-2-one, imidazolidine-2-one, piperidine, piperazine, piperazine-2-one, morpholine, morpholine-3-one, morpholine-2-one, thiomorpholine-3- one 1,1-dioxide, thiomorpholine, thiomorpholine-1,1-dioxide, tetrahydropyran, 1,2- dihydroazetidine, 1,2-dihydrooxetadiene, 2,5-dihydro-1H-pyrrole, 2,5-dihydrofuran, 2,3- dihydrofuran, 2,3-dihydro-1H-pyrrole, 3,4-dihydro-2H-pyran, 1,2,3,4-tetrahydropyridine, 3,6- dihydro-2H-pyran, 1,2,3,6-tetrahydropyridine, 1,3-oxazinane, hexahydropyrimidine, 1,4-dioxane, tetrahydropyrimidine-2(1H)-one, 1,4-dioxane-2-one, and 5,6-dihydro-2H-pyran-2-one; the 5- to 6- membered heterocycloalkyl is unsubstituted or substituted with 1, 2, 3 or 4 substituents each independently selected from group S.

21. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-11 and 14 characterized in that R 0 is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazolyl or substituted or unsubstituted tetrahydropyrrolyl; the "substituted" means that 1, 2, 3 or 4 hydrogen atoms in the group are substituted with substituent(s) each independently selected from group S.

22. The compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to claim 1, wherein the compound is selected from the following group: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] 212 [Image disponible dans le document PDF, Image available in the PDF document] 213 [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] 216 [Image disponible dans le document PDF, Image available in the PDF document] •23. A pharmaceutical composition, the pharmaceutical composition comprises the compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-22 and a pharmaceutically acceptable carrier.

24. Use of the compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-22, or the pharmaceutical composition according to claim 23 in the manufacture of a medicament for preventing and / or treating diseases, the diseases are selected from stroke, inflammatory bowel disease, psoriasis, rheumatoid arthritis, NASH and heart failure.

25. Use of the compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-22, or the pharmaceutical composition according to claim 23 for prevention and / or treatment of diseases, the diseases are selected from stroke, inflammatory bowel disease, psoriasis, rheumatoid arthritis, NASH and heart failure.

26. Use of claim 24 or 25, wherein the diseases are selected from ulcerative colitis and Crohn's disease.

27. Use of the compound or the pharmaceutically acceptable salt, the stereoisomer, or the solvate thereof according to any one of claims 1-22, or the pharmaceutical composition according to claim 23 in the manufacture of a selective inhibitor of RIPK1 for treatment of RIPK1-related diseases or conditions.