Search

CN-121991061-A - Heteroaryl-containing compounds, preparation method and application thereof

CN121991061ACN 121991061 ACN121991061 ACN 121991061ACN-121991061-A

Abstract

The invention relates to heteroaryl-containing compounds, a preparation method and application thereof. In particular, the invention relates to a compound shown in a general formula (I), a preparation method thereof, a pharmaceutical composition containing the compound and application thereof in preparing medicines for treating nervous system diseases, wherein each substituent in the general formula (I) is as defined in the specification.

Inventors

  • XIAO HUALING
  • WU GUOLIN
  • WANG LONGCHENG
  • XING JING
  • WU JIANRUI

Assignees

  • 江苏豪森药业集团有限公司
  • 上海翰森生物医药科技有限公司

Dates

Publication Date
20260508
Application Date
20251107
Priority Date
20241108

Claims (10)

  1. 1. A compound of the general formula (III') or a pharmaceutically acceptable salt thereof: ; Wherein, the Ring a or ring B are each independently selected from aryl, heterocyclyl or heteroaryl; R 1 or R 2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylamino, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein the amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylamino, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with one or more substituents of deuterium, halogen, oxo, nitrile, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylamino, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl; Or wherein R 2 and R 1 、L 1 or L 2 , respectively, form with the attached atom a cycloalkyl, heterocyclyl, aryl or heteroaryl group, wherein said cycloalkyl, heterocyclyl, aryl or heteroaryl group is optionally substituted with one or more R 5 substituents; R 5 is each independently selected from hydrogen, deuterium, halogen, oxo, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylamino, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl; Or any two R 5 together with the attached atoms form cycloalkyl, heterocyclyl, aryl, or heteroaryl, optionally substituted with one or more substituents from the group of deuterium, hydroxy, halogen, cyano, amino, alkyl, haloalkyl, alkoxy, alkylamino, haloalkoxy, hydroxyalkyl, or cyano-substituted alkyl; L 1 is selected from the group consisting of a bond, -NH-, -C (O) -, -S (O) 2 -、-NHS(O) 2 -, -NHC (O) -, -C (S) -, alkylene, cycloalkylene, heterocyclylene, or heteroarylene, said alkylene, cycloalkylene, heterocyclylene, or heteroarylene optionally substituted with one or more substituents of deuterium, halogen, oxo, nitrile, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylamino, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl; L 2 or L 3 are each independently selected from the group consisting of bond, -C (O) -, -NHC (O) -, alkylene, haloalkylene, cycloalkylene, heterocyclylene, heteroarylene, -NH (CR m R n ) n1 -or- (CR m R n ) n1 -, said alkylene, haloalkylene, cycloalkylene or heterocyclylene optionally substituted with one or more substituents of deuterium, halogen, oxo, nitrile, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkylamino, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl; R m or R n are each independently selected from hydrogen, deuterium, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino, haloC 1-6 alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-12 aryl, or 5-12 membered heteroaryl; Or R m 、R n together with the attached carbon atom forms a C 3-6 cycloalkyl group or a 4-6 membered heterocyclyl group containing 1-2 atoms selected from N, O or S (O) n ; R 3 、R 4 or R 3' are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, said amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl, optionally substituted with one or more substituents of deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl; Or R 3 and R 4 form with adjacent carbon atoms cycloalkyl, heterocyclyl, aryl or heteroaryl, optionally substituted with one or more substituents from the group consisting of deuterium, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl; When R 3 and R 4 form an aryl or heteroaryl group with the adjacent carbon atom, R 3' is absent; y or z is each independently selected from 0,1, 2, 3 or 4.
  2. 2. A compound or pharmaceutically acceptable salt thereof according to claim 1, Ring B is selected from 3-14 membered heterocyclyl containing 1-3N, O or S atoms, C 6-12 aryl or 5-14 membered heteroaryl containing 1-3N, O or S atoms, said 3-14 membered heterocyclyl containing 1-3N, O or S atoms, C 6-12 aryl or 5-14 membered heteroaryl containing 1-3N, O or S atoms optionally substituted by one or more substituents from the group consisting of deuterium, oxo, thio, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, C 1-6 hydroxyalkyl or cyano-substituted C 1-6 alkyl; Preferably, ring B is selected from 3-10 membered heterocyclyl containing 1-3N, O or S atoms, C 6-12 aryl or 5-12 membered heteroaryl containing 1-3N, O or S atoms, said 3-10 membered heterocyclyl containing 1-3N, O or S atoms, C 6-12 aryl or 5-12 membered heteroaryl containing 1-3N, O or S atoms optionally substituted by one or more substituents selected from deuterium, oxo, thio, halogen, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-3 alkenyl, C 2-3 alkynyl, C 1-3 haloalkyl, C 1-3 alkoxy, halogenated C 1-3 alkoxy, C 1-3 hydroxyalkyl or cyano substituted C 1-3 alkyl; More preferably, ring B is monocyclic, bicyclic or tricyclic, when ring B is monocyclic, is selected from 3-6 membered heterocyclyl containing 1-3N, O or S atoms, phenyl or 5-6 membered heteroaryl containing 1-3N, O or S atoms, when ring B is bicyclic, is selected from 4-10 membered fused heterocyclyl containing 1-3N, O or S atoms, 5-10 membered bridged heterocyclyl containing 1-3N, O or S atoms, 5-10 membered spirocycloalkyl containing 1-3N, O or S atoms, naphthyl or 8-10 membered fused heteroaryl containing 1-3N, O or S atoms, and when ring B is tricyclic, is selected from 7-14 membered heterocyclyl containing 1-3N, O or S atoms or 12-14 membered heteroaryl containing 1-3N, O or S atoms; further preferably, ring B is selected from phenyl, pyrimidine, pyridazine, pyrazine, pyridinyl, 、 Or (b) ; Even more preferred 、 、 、 、 Or (b) ; Represents a site linked to L3, and if L3 is a bond, represents a site linked to the ring A.
  3. 3. A compound or pharmaceutically acceptable salt thereof according to claim 1, Ring a is selected from 3-10 membered heterocyclyl containing 1-3N, O or S atoms, C 6-12 aryl or 5-12 membered heteroaryl containing 1-3N, O or S atoms, said 3-10 membered heterocyclyl containing 1-3N, O or S atoms, C 6-12 aryl or 5-12 membered heteroaryl containing 1-3N, O or S atoms optionally substituted by one or more substituents from the group consisting of deuterium, oxo, thio, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, halogenated C 1-6 alkoxy, C 1-6 hydroxyalkyl or cyano-substituted C 1-6 alkyl; Preferably, ring A is selected from phenyl, a 5-6 membered monocyclic heteroaryl group containing 1-3N, O or S atoms, a 7-10 membered bicyclic heteroaryl group containing 1-3N, O or S atoms, a 7-10 membered bicyclic heterocyclyl group containing 1-3N, O or S atoms, a 10-14 membered tricyclic heterocyclyl group containing 1-4N, O or S atoms; more preferably phenyl group, 、 、 、 、 、 、 、 、 、 、 、 Pyrimidine, pyridazine, pyrazine, pyridinyl, 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 Or (b) 。
  4. 4. A compound or pharmaceutically acceptable salt thereof according to claim 1, L 1 is selected from the group consisting of a bond, -NH-, -C (O) -, -C (S) -, -S (O) 2 -、-NHS(O) 2 -、- NHC(O)-、C 1-6 alkylene, C 3-10 cycloalkylene, 3-10 membered heterocyclylene, or 5-10 membered heteroarylene, said C 3-10 cycloalkylene, 3-10 membered heterocyclylene, or 5-10 membered heteroarylene optionally substituted with one or more substituents selected from deuterium, halogen, oxo, nitrile, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 haloalkoxy, C 1-6 hydroxyalkyl, C 1-6 cyano-substituted alkyl, C 3-10 cycloalkyl, 3-10 membered heterocyclyl, C 6-10 aryl, or 5-10 membered heteroaryl; Preferably, L 1 is selected from the group consisting of bond, -NH-, -C (O), -C (S) -, -S (O) 2 -、-NHS(O) 2 -、- NHC(O)- 、C 1-3 alkylene, or a 3-10 membered heterocyclylene group containing 1-3N, O or S atoms, said 3-10 membered heterocyclylene group optionally being further substituted with one or more substituents of deuterium, halogen, oxo, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 alkylamino, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl; More preferably, L 1 is selected from the group consisting of a bond, -NH-, -C (O), -C (S) -, -S (O) 2 -、-NHS(O) 2 -, -NHC (O) -, methylene, ethylene, propylene, 3-6 membered monoheterocyclylene selected from the group consisting of 1-3N, O or S atoms, 4-10 membered fused heterocyclylene selected from the group consisting of 1-3N, O or S atoms, 1-3N, A 5-10 membered bridged heterocyclyl group of O or S atoms or a 5-10 membered spirocycloalkyl group containing 1-3N, O or S atoms, said methylene, ethylene, propylene, 3-6 membered monoheterocyclylene group selected from the group consisting of 1-3N, O or S atoms, 4-10 membered fused heterocyclyl group selected from the group consisting of 1-3N, O or S atoms, 5-10 membered bridged heterocyclyl group containing 1-3N, O or S atoms or 5-10 membered spirocycloalkyl group containing 1-3N, O or S atoms being optionally further substituted by deuterium, halogen, oxo, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 alkylamino, Further preferably L 1 is selected from the group consisting of a bond, -NH-, -C (O), -C (S) -, -S (O) 2 -、-NHS(O) 2 -, and, NHC (O) -, methylene, ethylene, propylene, a 5-6 membered monoheterocyclylene group selected from 1-3N, O or S atoms, a 5-10 membered fused heterocyclylene group selected from 1-3N, O or S atoms, a 6-10 membered bridged heterocyclylene group selected from 1-3N, O or S atoms, or a 6-10 membered spiroalkylene group selected from 1-3N, O or S atoms, said methylene, ethylene, propylene, a 5-6 membered monoheterocyclylene group selected from 1-3N, O or S atoms, a 5-10 membered fused heterocyclylene group selected from 1-3N, O or S atoms, a 6-10 membered bridged heterocyclylene group selected from 1-3N, O or S atoms, or a 6-10 membered spiroalkylene group selected from 1-3N, The 6-to 10-membered spirocyclic alkyl group of O or S atom is optionally further substituted by deuterium, halogen, oxo, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 haloalkyl, One or more substituents selected from C 1-3 alkoxy, C 1-3 alkylamino, halogenated C 1-3 alkoxy, and C 1-3 hydroxyalkyl; Still more preferably, L 1 is selected from the group consisting of a bond, -NH-, -C (O), -S (O) 2 -、-NHS(O) 2 -, -NHC (O) -, methylene, or a 5-6 membered heterocyclylene group containing 1-2N, O or S atoms; still more preferably, L 1 is selected from the group consisting of bond, -C (O) -, -NHC (O) -, methylene, 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 A cyclopropylene group, a cyclobutylene group, a cyclopentylene group, a cyclohexylene group, 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 Or (b) ; Or L 2 or L 3 are each independently selected from the group consisting of bond, -C (O) -, -NHC (O) -, C 1-6 alkylene, C 1-6 haloalkylene, C 3-10 cycloalkylene, 3-10 membered heterocyclylene, -N (CR m R n ) n1 -or- (CR m R n ) n1 -, said C 1-6 alkylene, C 1-6 haloalkylene, C 3-10 cycloalkylene, or 3-10 membered heterocyclylene, optionally substituted with one or more substituents of deuterium, halogen, oxo, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 alkylamino, halogenated C 1-3 alkoxy, C 1-3 hydroxyalkyl); Preferably, each L 2 or L 3 is independently selected from the group consisting of bond, -C (O) -, C 1-3 alkylene, C 3-6 cycloalkylene, 3-6 membered heterocyclylene containing 1-3N, O or S atoms, -N (CR m R n ) n1 -or- (CR m R n ) n1 -, said 3-6 membered heterocyclylene optionally further substituted with one or more substituents of deuterium, halogen, oxo, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 alkylamino, halogenated C 1-3 alkoxy, C 1-3 hydroxyalkyl; More preferably, each L 2 or L 3 is independently selected from the group consisting of bond, -C (O) -, C 1-3 alkylene, C 3-6 cycloalkylene, 5-6 membered heterocyclylene containing 1-3N, O or S atoms, -N (CR m R n ) n1 -or- (CR m R n ) n1 -, said 5-6 membered heterocyclylene optionally further substituted with one or more substituents of deuterium, halogen, oxo, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 alkylamino, halogenated C 1-3 alkoxy, C 1-3 hydroxyalkyl; more preferably, L 2 is selected from 、 、 、 、 Methylene, ethylene or-NHCH 2 CH 2 -; Or L 3 is selected from a bond or C 1-3 alkylene.
  5. 5. A compound or pharmaceutically acceptable salt thereof according to claim 1, R 1 or R 2 are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino, halogenated C 1-6 alkoxy, C 1-6 hydroxyalkyl, cyano-substituted C 1-6 alkyl, C 3-12 cycloalkyl, 3-12 membered heterocyclyl, C 6-12 aryl, or 5-12 membered heteroaryl; Preferably, each R 1 or R 2 is independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 alkylamino, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-10 cycloalkyl, 3-to 10-membered heterocyclyl containing 1-3 atoms selected from N, O or S atoms, C 6-10 aryl, or 5-to 10-membered heteroaryl containing 1-3 atoms selected from N, O or S atoms; More preferably, R 1 or R 2 are each independently selected from hydrogen, deuterium, or methyl; Or R 2 and R 1 form a C 5-10 cycloalkyl group or a 5-10 membered heterocyclic group containing 1-3 atoms selected from C (O), N, O or S.
  6. 6. A compound or pharmaceutically acceptable salt thereof according to claim 1, R 3 、R 4 or R 3' are each independently selected from hydrogen, deuterium, halogen, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 haloalkyl, C 1-3 alkoxy, halo C 1-3 alkoxy, C 1-3 hydroxyalkyl, Cyano-substituted C 1-3 alkyl, C 3-10 cycloalkyl, 3-10 membered heterocyclyl containing 1 to 3 atoms selected from N, O or S, C 6-10 aryl or 5-10 membered heteroaryl containing 1 to 3 atoms selected from N, O or S, said amino group, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 haloalkyl, C 1-3 alkoxy, Halogenated C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-10 cycloalkyl, 3-10 membered heterocyclyl containing 1-3 atoms selected from N, O or S atoms, C 6-10 aryl, or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S atoms, optionally substituted with one or more substituents selected from deuterium, hydroxy, halogen, cyano, amino, C 1-3 alkyl, C 1-3 haloalkyl; preferably, R 3 is hydrogen or deuterium; R 4 is selected from C 1-3 haloalkyl or phenyl or C 3-6 cycloalkyl substituted with one or more substituents of fluoro, chloro, bromo, cyano, amino, C 1-3 alkyl, C 1-3 haloalkyl; Or R 3 and R 4 together with the atom to which they are attached form a C 3-7 cycloalkyl group, 1-3 4-10 membered heterocyclyl groups selected from N, O or S atoms, a C 6-10 aryl group or a 5-6 membered heteroaryl group containing 1-3 atoms selected from N, O or S atoms, optionally substituted with one or more substituents of deuterium, hydroxy, halogen, cyano, amino, C 1-3 alkyl, C 1-3 haloalkyl, preferably, or R 3 together with R 4 together with the atom to which they are attached form a cyclopropyl, phenyl or pyridine, optionally substituted with one or more substituents of deuterium, hydroxy, fluoro, chloro, cyano, amino, C 1-3 alkyl, C 1-3 haloalkyl.
  7. 7. The compound according to any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (III') is further represented by formula (IV-1), (IV-2) or (IV-3): 、 、 ; Wherein, the M 1 or M 2 are each independently selected from the group consisting of a bond, O, S, C (O), NH, NHC (O), -OCH 2 -, or (CH 2 ) m , and at least one of M 1 or M 2 is not a bond; r 5 is each independently selected from hydrogen, deuterium, halogen, oxo, amino, hydroxy, cyano, nitro, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 haloalkyl, C 1-3 alkoxy, C 1-3 alkylamino, halogenated C 1-3 alkoxy, C 1-3 hydroxyalkyl, cyano-substituted C 1-3 alkyl, C 3-10 cycloalkyl, 3-10 membered heterocyclyl containing 1-3 atoms selected from N, O or S atoms, C 6-10 aryl, or 5-10 membered heteroaryl containing 1-3 atoms selected from N, O or S atoms; Or any two R 5 together with the attached atoms form a C 3-6 cycloalkyl, a 5-6 membered monocyclic heterocyclyl containing 1-3N, O or S atoms, or a 5-6 membered monocyclic heteroaryl containing 1-3N, O or S atoms, optionally substituted with one or more substituents of deuterium, hydroxy, halogen, cyano, amino, C 1-3 alkyl, C 1-3 haloalkyl; m is 1, 2 or 3; x is 0,1, 2, 3 or 4; Preferably, the compound is further represented by the general formulA (IV-A), (IV-B) or (IV-C): 、 、 ; represents an aromatic ring or a non-aromatic ring; M 1 or M 2 are each independently selected from the group consisting of a bond, O, S, C (O), NH or CH 2 , and at least one of M 1 or M 2 is not a bond; T 1 、T 2 、M 3 、M 4 、M 5 、M 6 、M 7 or M 8 are each independently selected from a bond, O, S, C (O), N or C; T 3 、T 4 、T 5 or T 6 are each independently selected from N or C; T 7 is selected from N or C, ring C is selected from C 3-6 cycloalkyl, 1-3 4-10 membered heterocyclyl selected from N, O or S atom, C 6-10 aryl or 5-6 membered heteroaryl containing 1-3 atoms selected from N, O or S atom, optionally substituted with one or more substituents of hydroxy, deuterium, halogen, cyano, amino, C 1-3 alkyl, C 1-3 haloalkyl, preferably cyclopropyl, phenyl or pyridine, optionally substituted with one or more substituents of deuterium, hydroxy, fluorine, chlorine, cyano, amino, C 1-3 alkyl, C 1-3 haloalkyl.
  8. 8. A compound or a pharmaceutically acceptable salt thereof as shown below, the specific structure of the compound being as follows: 。
  9. 9. A pharmaceutical composition comprising a therapeutically effective amount of a compound as set forth in any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or excipients.
  10. 10. The use of a compound as set forth in any one of claims 1-8 or a pharmaceutically acceptable salt thereof or a pharmaceutical composition as set forth in claim 9 for the manufacture of a medicament for the treatment of a disease associated with SARM1, preferably a disease associated with SARM1 is selected from neurological diseases, more preferably Spinal Muscular Atrophy (SMA), chemotherapy-induced peripheral neuropathy, multiple Sclerosis (MS), traumatic Brain Injury (TBI), spinal cord injury, stroke, parkinson's disease, glaucoma, huntington's disease, alzheimer's disease, fibular muscular atrophy (CMT), retinitis Pigmentosa (RP), age-related macular degeneration (AMD), small-fiber neuropathy, peripheral neuropathy (e.g., viral neuropathy), spinocerebellar ataxia, cystic fibrosis, familial amyloid polyneuropathy, spongiform encephalopathy, spinal and bulbar atrophy, hereditary dentate nucleus erythroosis-pallidum atrophy, adrenoleukodystrophy, adrenomyeloneuropathy, alexander's disease, amyotrophic Lateral Sclerosis (ALS), bassen-Kornzweig syndrome, bell palsy, progressive Supranuclear Palsy (PSP), pontine central myelolysis, cluster headache, congenital myelin deficiency, corticobasal degeneration, creutzfeldt-Jakob disease, epilepsy, dementia (e.g., frontotemporal dementia and lewy body dementia), demyelinating diseases (e.g., ischemic demyelination), encephalomyelitis, friedel-crafts ataxia, gaucher's disease, hereditary Sensory and Autonomic Neuropathy (HSAN), hurler syndrome, creper's disease, metachromatic leukodystrophy, sex-acquired encephalopathy, migraine and tension headache, mild cognitive impairment, motor spinal neuronal disorders, neuromyelitis optica, niemann-pick disease, optic neuritis, petunia Li Zawu s·mezhibach disease, peripheral neuropathy, periventricular leukomalacia, postherpetic neuralgia, prion diseases, progressive supranuclear palsy, progressive multifocal leukoencephalopathy, tay-Sacks disease, herniated thoracic disc, transverse myelitis, trigeminal neuralgia, warrior degeneration, cerebellar degeneration, chiari deformity, dystonia, encephalitis (e.g. pediatric and rakes virus encephalitis), overconvulsions, multifocal motor neuropathy, muscular dystrophy, myasthenia gravis, myopathy, neuro-fibromatosis, neuronal ceroid lipofuscinosis, neuropathy (e.g. peripheral neuropathy), pseudobulbar effect, restless leg syndrome, spinal fissures, syringomyelia, thoracic outlet syndrome, and transverse myelitis.

Description

Heteroaryl-containing compounds, preparation method and application thereof Technical Field The invention belongs to the field of biological medicine, and in particular relates to a heteroaryl-containing compound, a preparation method and application thereof. Background In many neurodegenerative diseases and nerve injuries, degeneration of the nerve axon is a pathological change that occurs at an early stage. Its appearance is often predictive of irreversible nerve damage and neuronal death. The current treatment of neurodegenerative diseases is often limited to relief from the corresponding symptoms, and treatment of the etiology and progression of the disease is far from being achieved. How to effectively prevent and control the degeneration of nerve axons provides a new treatment path for the treatment of various neurodegenerative diseases and nerve injuries, and relieves and blocks the progress of the diseases. SARM1 is a class of hydrolytic enzymes expressed in neurons and glial cells that hydrolyze nicotinamide adenine dinucleotide (nicotinamide adenine dinucleotide, nad+) as a substrate to Nicotinamide (NAM), adenosine diphosphate ribose (adenosine diphosphate ribose, ADPR), and cyclic adenosine diphosphate ribose (cADPR). SARM1 activates when nerves are damaged, a large amount of hydrolyzed nad+ reduces intracellular nad+ levels, causing cell metabolic disorders, and its hydrolyzate cADPR causes elevated cytoplasmic calcium ion concentrations by modulating endoplasmic reticulum ryanodine receptor and TRPM2 calcium channels, ultimately leading to programmed axonal degeneration and axonal loss. SARM1 inhibitors are useful in the treatment of axonal degeneration lesions. SARM1 is a multi-domain enzyme comprising 724 amino acids, consisting of an amino-terminal ARM (Armadillo repeat) domain, a continuous repeat SAM (STERILE ALPHA motif) domain that oligomerizes kinesin, and a carboxy-terminal TIR (Toll/interleukin-1 receptor) enzyme domain that catalyzes the hydrolysis of NAD+. ARM domains are self-inhibitory and thus modulate the activity of SARM1, and truncating ARM results in SARM1 activation. In physiological states, SARM1 exhibits a lower basal level of enzyme activity due to ARM binding directly to TIR and inhibiting its catalytic activity. Upon SARM1 activation, ARM's inhibition of TIR is blocked, activating the programmed axonal degeneration signaling pathway. SARM1 inhibitors may act to protect axons by inhibiting the catalytic activity of SARM1 or by blocking SARM1 activation by maintaining SARM1 in a self-inhibiting state. SARM1 enzyme activity is significantly enhanced in chemotherapy-induced peripheral neuropathy (chemotherapy-induced peripheral neuropathy, CIPN), painful diabetic neuropathy (painful diabetic neuropathy, PDN), alzheimer's Disease (AD), parkinson's Disease (PD), huntington's Disease (HD), amyotrophic lateral sclerosis (amyotrophic lateral sclerosis, ALS), spinal muscular atrophy (spinal muscular atrophy), multiple sclerosis (multiple sclerosis, MS), traumatic brain injury (traumatic brain injury, TBI), ischemic stroke (ischemictaste stroke), and glaucoma (glaucoma) to cause degeneration of axons and loss of axons, and thus the development of SARM1 inhibitors is helpful in the treatment of these diseases. Disclosure of Invention The invention aims to provide a compound shown in a general formula (I) or pharmaceutically acceptable salt thereof: Ring a is selected from cycloalkyl, heterocyclyl, aryl or heteroaryl optionally substituted with one or more substituents of halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl, alkenylcarboxyl or alkynylcarboxyl; L is selected from the group consisting of a bond 、-C(O)-、-NR11C(O)-、-C(O)NR11-、-NR11C(O)NR22-、-OC(O)NR22-、-SC(O)NR22-、-NR11C(O)O-、-NR11C(O)S-、-NR11C(S)-、-C(S)NR11-、-NR11C(S)NR22-、-OC(S)NR22-、-SC(S)NR22-、-NR11C(S)O-、-NR11C(S)S-、 heterocyclylene or heteroarylene, wherein said heterocyclylene or heteroarylene is optionally substituted with one or more substituents of oxo, thioxo, halo, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, or cyano-substituted alkyl; R 11 or R 22 are each independently selected from hydrogen, halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, said amino, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl optionally substituted with one or more substituents of halogen, amino, hydroxy, cyano, nitro, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, cyano-substituted alkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl; r 1 or R 2 are each independently selected from hydrogen, halogen,