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CN-121986094-A - Heterocyclic compound, composition and application thereof

CN121986094ACN 121986094 ACN121986094 ACN 121986094ACN-121986094-A

Abstract

The invention provides a heterocyclic compound, a composition and application thereof. Specifically provided are compounds represented by formula II or pharmaceutically acceptable salts thereof. The compound has one or more of the following advantages of novel structure, high efficiency and high selectivity for degrading IKZF2, inhibiting and regulating the function of T cells, and great clinical development value when applied to treating tumors or diseases.

Inventors

  • XIANG SHAOYUN
  • WU LEI
  • LIU YUXIN
  • YANG MENG
  • ZHANG BING
  • CHEN YUFENG
  • YANG RUI

Assignees

  • 杭州多域生物技术有限公司

Dates

Publication Date
20260505
Application Date
20240927
Priority Date
20230928

Claims (14)

  1. A compound of formula II or a pharmaceutically acceptable salt thereof; wherein q is 0,1,2 or 3; R 3 is H, -OH or halogen; Y 1 is CR Y1 or N; Y 2 is CR Y2 or N; y 3 is CR Y3 or N; R Y1 、R Y2 and R Y3 are each independently H, NR a R b 、OR a or halogen; Q is CR Q1 R Q2 ; R Q1 and R Q2 are independently H, deuterium or C 1 -C 6 alkyl; R X is H or deuterium; Each R 1 is independently C 1 -C 6 alkyl or halogen; The ring A is 3-12 membered heterocycloalkylene or 3-12 membered heterocycloalkenylene, wherein in the 3-12 membered heterocycloalkylene and 3-12 membered heterocycloalkenylene, the number of hetero atoms is 1,2 or 3 respectively and independently, the hetero atoms are 1,2 or 3 respectively and independently selected from N, O and S, and at least one hetero atom is N; R 2 is C 3 -C 10 monocyclic cycloalkyl, C 5 -C 10 polycyclic cycloalkyl, 3-12 membered heterocycloalkyl, C 3 -C 10 monocyclic cycloalkyl substituted by one or more R 2-1 , C 1 -C 6 alkyl substituted by one or more R 2-2 , 3-12 membered heterocycloalkyl substituted by one or more R 2-3 or C 5 -C 10 polycyclic cycloalkyl substituted by one or more R 2-4 , wherein in the 3-12 membered heterocycloalkyl, the heteroatoms are independently selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is independently 1, 2 or 3; Each R 2-1 is independently OR a , -CONR a R b 、 CN, C 3 -C 10 cycloalkyl, 3-12 membered heterocycloalkyl, halogen, C 6 -C 10 aryl, 5-12 membered heteroaryl, C 1 -C 6 alkyl, C 6 -C 10 aryl substituted with one or more R 2- 1-1 , C 1 -C 6 alkyl substituted with one or more R 2-1-2 , or 5-12 membered heteroaryl substituted with one or more R 2-1-3 , wherein in the 5-12 membered heteroaryl, the heteroatoms are each independently selected from 1, 2, or 3 of N, O and S, the number of heteroatoms is each independently 1, 2, 3, or 4, and wherein in the 3-12 membered heterocycloalkyl, the heteroatoms are selected from 1, 2, or 3 of N, O and S, and the number of heteroatoms is 1, 2, or 3; Each R 2-4 is independently OR a , -CONR a R b 、 CN, C 3 -C 10 cycloalkyl, 3-12 membered heterocycloalkyl, halogen, C 6 -C 10 aryl, 5-12 membered heteroaryl, C 1 -C 6 alkyl, C 6 -C 10 aryl substituted with one or more R 2- 1-1 , C 1 -C 6 alkyl substituted with one or more R 2-1-2 , or 5-12 membered heteroaryl substituted with one or more R 2-1-3 , wherein in the 5-12 membered heteroaryl, the heteroatoms are each independently selected from 1, 2, or 3 of N, O and S, the number of heteroatoms is each independently 1, 2, 3, or 4, and wherein in the 3-12 membered heterocycloalkyl, the heteroatoms are selected from 1, 2, or 3 of N, O and S, and the number of heteroatoms is 1, 2, or 3; Each R 2-1-1 is independently halogen, cyano, OR a , A C 1 -C 6 alkyl or a C 1 -C 6 alkyl substituted with one or more halogens; Each R 2-1-2 is independently halogen, OR a , C 3 -C 10 cycloalkyl, 3-12 heterocycloalkyl, C 6 -C 10 aryl or 5-12 membered heteroaryl, wherein in the 3-12 membered heterocycloalkyl, the heteroatom is 1,2 or 3 in N, O and S, the heteroatom is 1,2 or 3, and in the 5-12 membered heteroaryl, the heteroatom is 1,2 or 3 in N, O and S, the heteroatom is 1,2, 3 or 4; Each R 2-1-3 is independently halogen, cyano, OR a , A C 1 -C 6 alkyl or a C 1 -C 6 alkyl substituted with one or more halogens; Each R 2-2 is independently halogen, OR a , A C 3 -C 10 monocyclic cycloalkyl substituted by one or more R 2-2-1 , a C 5 -C 10 polycyclic cycloalkyl substituted by one or more R 2-2-2 or a 3-12 membered heterocycloalkyl substituted by one or more R 2-2-3 , wherein the heteroatoms in the 3-12 membered heterocycloalkyl are selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3; each R 2-2-1 is independently halogen, OR a , A C 6 -C 10 aryl group, a 5-12 membered heteroaryl group or a C 1 -C 6 alkyl group, wherein in the 5-12 membered heteroaryl group, a heteroatom is selected from 1,2 or 3 of N, O and S, and the number of the heteroatom is 1,2, 3 or 4; Each R 2-2-2 is independently halogen, OR a , A C 6 -C 10 -12 membered heteroaryl group, a C 1 -C 6 alkyl group or a C 1 -C 6 alkyl group substituted with one or more halogens, wherein the heteroatoms in the 5-12 membered heteroaryl group are selected from 1,2 or 3 of N, O and S, and the number of heteroatoms is 1,2, 3 or 4; each R 2-2-3 is independently halogen, OR a , Oxo, C 6 -C 10 aryl, 5-12 membered heteroaryl, C 1 -C 6 alkyl or C 1 -C 6 alkyl substituted by one or more halogens, wherein in the 5-12 membered heteroaryl, the hetero atom is selected from 1,2 or 3 in N, O and S, and the hetero atom number is 1,2, 3 or 4; Each R 2-3 is independently oxo (=O), -C (=O) OR a 、-C(＝O)R a , -CONR a R b 、 Halogen, OR a 、CN、C 3 -C 10 cycloalkyl, 3-12 membered heterocycloalkyl, and, A C 6 -C 10 aryl group, a 5-12 membered heteroaryl group substituted with one or more R a , a C 6 -C 10 aryl group substituted with one or more R 2-3-1 , or a C 1 -C 6 alkyl group substituted with one or more R 2-3-2 , wherein the 5-12 membered heteroaryl group has a heteroatom independently selected from 1,2, or 3 of N, O and S, the heteroatom independently selected from 1,2, 3, or 4 of S, and the 3-12 membered heterocycloalkyl group has a heteroatom independently selected from 1,2, or 3 of N, O and S, and the heteroatom is 1,2, or 3 of; Each R 2-3-1 is independently halogen, cyano, OR a , Or C 1 -C 6 alkyl substituted with one or more halogens; Each R 2-3-2 is independently halogen, OR a , C 3 -C 10 cycloalkyl, 3-12 heterocycloalkyl, C 6 -C 10 aryl or 5-12 membered heteroaryl, wherein in the 3-12 membered heterocycloalkyl, the heteroatom is 1,2 or 3 in N, O and S, the heteroatom is 1,2 or 3, and in the 5-12 membered heteroaryl, the heteroatom is 1,2 or 3 in N, O and S, the heteroatom is 1,2, 3 or 4; Each R a is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by one or more halogens, C 3 -C 10 cycloalkyl or 3-12 membered heterocycloalkyl, wherein in the 3-12 membered heterocycloalkyl, the heteroatoms are selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3; Each R b is independently hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkyl substituted by one or more halogens, C 3 -C 10 cycloalkyl or 3-12 membered heterocycloalkyl, wherein in the 3-12 membered heterocycloalkyl, the heteroatoms are selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2 or 3; Or R a 、R b and the atoms connected with the R a 、R b form 3-12 membered heterocycloalkyl, wherein in the 3-12 membered heterocycloalkyl, the heteroatom is selected from 1,2 or 3 in N, O and S, and the number of the heteroatom is 1,2 or 3.
  2. A compound of formula II or a pharmaceutically acceptable salt thereof as claimed in claim 1 which satisfies one or more of the following conditions: (1) In R 3 , the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (2) In R Y1 , the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (3) In R Y3 , the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (4) In R 1 , the C 1 -C 6 alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, preferably methyl; (5) In R 1 , the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (6) In ring A, the hetero atom of the 3-12 membered heterocycloalkylene group is 1 or 2 of N, O and S, the hetero atom number of the 3-12 membered heterocycloalkylene group is preferably 1 or 2, the 3-12 membered heterocycloalkylene group is more preferably 4-10 membered heterocycloalkylene group, further preferably 4-7 membered monocycloheterocycloalkyl group or 7-10 membered bridged heterocycloalkylene group, for example Also e.g. for example (7) In ring A, the hetero atoms of the 3-12 membered heterocycloalkenylene group are each independently N, or N and O, the number of hetero atoms of the 3-12 membered heterocycloalkenylene group is preferably 1 or2, the 3-12 membered heterocycloalkenylene group is more preferably 6-10 membered heterocycloalkenylene group, further preferably 6-membered monocyclic heterocycloalkenylene group or 9-membered bridged heterocycloalkenylene group, for example Also e.g. for example (8) In R 2 , the C 3 -C 10 monocyclic cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; (9) In R 2 , the C 5 -C 10 polycyclic cycloalkyl radicals are each independently of the others For example (10) In R 2 , the hetero atom of the 3-12 membered heterocycloalkyl group is each independently 1 or 2 of N, O and S, the hetero atom number of the 3-12 membered heterocycloalkyl group is preferably 1 or 2, the 3-12 membered heterocycloalkyl group is more preferably 4-10 membered heterocycloalkyl group, further preferably 4-7 membered monocyclic heterocycloalkyl group, 7-10 membered bridged heterocycloalkyl group or 7-10 membered fused heterocycloalkyl group of the spiroheterocycloalkyl group, for example Also e.g. for example The said process Preferably is And/or (11) In R 2 , the C 1 -C 6 alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, preferably methyl; (12) In R 2-1 , the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (13) In R 2-1 , the C 6 -C 10 aryl groups are each independently phenyl or naphthyl, preferably phenyl; (14) In R 2-1 , the heteroatoms of the 5-12 membered heteroaryl are each independently N and/or O, the number of heteroatoms of the 5-12 membered heteroaryl is preferably 1 or 2, the 5-12 membered heteroaryl is more preferably 6-9 membered heteroaryl, further preferably 6 membered monocyclic heteroaryl or 9 membered bicyclic heteroaryl, for example Also e.g. for example (15) In R 2-1 , the C 1 -C 6 alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, preferably methyl; (16) In R 2-4 , the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (17) In R 2-1-1 , the C 1 -C 6 alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, preferably methyl; (18) In R 2-1-1 , the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (19) In R 2-1-2 , the C 6 -C 10 aryl groups are each independently phenyl or naphthyl, preferably phenyl; (20) In R 2-1-3 , the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (21) In R 2-2 , the C 3 -C 10 monocyclic cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; (22) In R 2-2-1 , the C 6 -C 10 aryl groups are each independently phenyl or naphthyl, preferably phenyl; (23) In R 2-3 , the C 6 -C 10 aryl groups are each independently phenyl or naphthyl, preferably phenyl; (24) In R 2-3 , the heteroatoms of the 5-12 membered heteroaryl are each independently N and/or O, the number of heteroatoms of the 5-12 membered heteroaryl is preferably 1 or 2, the 5-12 membered heteroaryl is more preferably a 6-9 membered heteroaryl, further preferably a 6 membered monocyclic heteroaryl, for example Also e.g. for example (25) In R 2-3-1 , the halogen is fluorine, chlorine, bromine or iodine, preferably fluorine; (26) In R a , the C 1 -C 6 alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, preferably methyl, isobutyl or tert-butyl; (27) The C 1 -C 6 alkyl groups are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert-butyl, preferably methyl, isobutyl or tert-butyl; (28) The halogens are each independently fluorine, chlorine, bromine or iodine, preferably fluorine; (29) The C 3 -C 10 monocyclic cycloalkyl groups are each independently cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; (30) The C 5 -C 10 polycyclic cycloalkyl radicals are each independently For example (31) The hetero atom of the 3-12 membered heterocycloalkyl group is 1 or 2 of N, O and S, the hetero atom number of the 3-12 membered heterocycloalkyl group is preferably 1 or 2, the 3-12 membered heterocycloalkyl group is more preferably 4-10 membered heterocycloalkyl group, further preferably 4-7 membered monocyclic heterocycloalkyl group, 7-10 membered spirocycloalkyl group, 7-10 membered bridged heterocycloalkyl group or 7-10 membered fused heterocycloalkyl group, for example Also e.g. for example The said process Preferably is And/or (32) The C 6 -C 10 aryl groups are each independently phenyl or naphthyl, preferably phenyl; (33) The heteroatoms of the 5-12 membered heteroaryl group are each independently N and/or O, the number of heteroatoms of the 5-12 membered heteroaryl group is preferably 1 or 2, the 5-12 membered heteroaryl group is more preferably a 6-9 membered heteroaryl group, further preferably a 6-membered monocyclic heteroaryl group or a 9-membered bicyclic heteroaryl group, e.g Also e.g. for example (34) The halogen in the C 1 -C 6 alkyl substituted with one or more halogens is fluorine, chlorine, bromine or iodine, preferably fluorine; (35) The C 1 -C 6 alkyl groups of the C 1 -C 6 alkyl groups substituted with one or more halogens are each independently methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, or tert-butyl; (36) The C 1 -C 6 alkyl substituted with one or more halogens is preferably-CF 3 .
  3. A compound of formula II or a pharmaceutically acceptable salt thereof as claimed in claim 1 which satisfies one or more of the following conditions: (1) q is 0, 1 or 2, preferably 0 or 1, more preferably 0; (2) R 3 is H; (3) Y 1 is CR Y1 ; (4) Y 2 is CR Y2 ; (5) Y 3 is CR Y3 ; (6) R Y1 and R Y2 are independently H or halogen, preferably H; (7) R Y3 is independently H or halogen; (8) R Q1 and R Q2 are independently H or deuterium, preferably hydrogen; (9) R X is H; (10) Each R 1 is independently C 1 -C 6 alkyl or halogen, preferably C 1 -C 6 alkyl; (11) Ring A is 3-12 membered heterocycloalkylene or 3-12 membered heterocycloalkenylene, preferably 3-12 membered heterocycloalkylene, wherein the 3-12 membered heterocycloalkylene and 3-12 membered heterocycloalkenylene are each independently 1,2 or 3 in number, and each heteroatom is independently selected from 1,2 or 3 of N, O and S, at least one heteroatom is N, more preferably 4-7 membered monocycloheterocycloalkyl or 7-10 membered bridged heterocycloalkylene, for example 4-7 membered monocycloheterocycloalkyl, and wherein the 4-7 membered monocycloheterocycloalkyl and 7-10 membered bridged heterocycloalkylene are each independently 1 or 2 in number, each heteroatom is each independently 1 or 2 of N, O and S, and at least one heteroatom is N; (12) R 2 is C 5 -C 10 polycyclocycloalkyl, 3-12 membered heterocycloalkyl, C 3 -C 10 monocyclocycloalkyl substituted by one or more R 2-1 , C 1 -C 6 alkyl substituted by one or more R 2-2 , 3-12 membered heterocycloalkyl substituted by one or more R 2-3 or C 5 -C 10 polycyclocycloalkyl substituted by one or more R 2-4 , wherein the 3-12 membered heterocycloalkyl is independently selected from 1, 2 or 3 of N, O and S, the number of heteroatoms is independently 1, 2 or 3, preferably C 5 -C 10 polycyclocycloalkyl, 7-10 membered spirocycloalkyl, 7-10 membered bridged heterocycloalkyl or C 5 -C 10 polycyclocycloalkyl substituted by one or more R 2-4 , the heteroatoms in the 7-10 membered spirocycloalkyl and 7-10 membered bridged heterocycloalkyl are independently selected from 1 or 2 of N, O and S, the number of heteroatoms is independently 1 or 2 of heteroatoms; (13) Each R 2-1 is independently-OH, halogen, C 6 -C 10 aryl, 5-12 membered heteroaryl, C 6 -C 10 aryl substituted by one or more R 2-1-1 , C 1 -C 6 alkyl substituted by one or more R 2-1-2 or 5-12 membered heteroaryl substituted by one or more R 2-1-3 , preferably C 6 -C 10 aryl or C 1 -C 6 alkyl substituted by one or more R 2-1-2 , wherein the heteroatoms in the 5-12 membered heteroaryl are selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is 1, 2, 3 or 4; (14) Each R 2-1-1 is independently C 1 -C 6 alkyl substituted with one or more halogens; (15) Each R 2-1-2 is independently C 6 -C 10 aryl; (16) Each R 2-1-3 is independently halogen; (17) Each R 2-4 is independently halogen, OR a , Or CN, preferably halogen; (18) Each R 2-2 is independently C 3 -C 10 monocyclic cycloalkyl substituted by one or more R 2-2-1 ; (19) Each R 2-2-1 is independently C 6 -C 10 aryl; (20) Each R 2-3 is independently oxo (=O), -C (=O) OR a 、-C(＝O)R a , C 6 -C 10 aryl, 5-12 membered heteroaryl OR C 6 -C 10 aryl substituted by one OR more R 2-3-1 , preferably-C (=O) OR a 、-C(＝O)R a , A C 6 -C 10 aryl group, a 5-12 membered heteroaryl group OR a C 6 -C 10 aryl group substituted by one OR more R 2-3-1 , more preferably a C 6 -C 10 aryl group OR a-C (=O) OR a , wherein in the 5-12 membered heteroaryl group, the heteroatom is selected from 1, 2 OR 3 of N, O and S, and the number of heteroatoms is 1, 2,3 OR 4; (21) Each R 2-3-1 is independently halogen OR OR a , preferably halogen; (22) Each R a is independently C 1 -C 6 alkyl or H; (23) The pharmaceutically acceptable salt of the compound shown in the formula II is formate.
  4. The compound of formula II or a pharmaceutically acceptable salt thereof according to claim 1, which is scheme a, scheme b or scheme c as follows; scheme a: q is 0,1 or 2; R 3 is H, -OH or halogen; Y 1 is CR Y1 ; Y 2 is CR Y2 ; y 3 is CR Y3 ; R Y1 、R Y2 and R Y3 are each independently H or halogen; Q is CR Q1 R Q2 ; r Q1 and R Q2 are independently H; R X is H; Each R 1 is independently C 1 -C 6 alkyl or halogen; the ring A is 3-12 membered heterocycloalkylene or 3-12 membered heterocycloalkenylene, wherein in the 3-12 membered heterocycloalkylene and 3-12 membered heterocycloalkenylene, the number of hetero atoms is independently 1,2 or 3, the hetero atoms are independently selected from 1,2 or 3 of N, O and S, and at least one hetero atom is N; r 2 is C 5 -C 10 polycyclic cycloalkyl, 3-12 membered heterocycloalkyl, C 3 -C 10 monocyclic cycloalkyl substituted by one or more R 2-1 , C 1 -C 6 alkyl substituted by one or more R 2-2 , 3-12 membered heterocycloalkyl substituted by one or more R 2-3 or C 5 -C 10 polycyclic cycloalkyl substituted by one or more R 2-4 , wherein the 3-12 membered heterocycloalkyl has 1,2 or 3 heteroatoms selected from N, O and S, and 1,2 or 3 heteroatoms; Each R 2-1 is independently-OH, halogen, C 6 -C 10 aryl, 5-12 membered heteroaryl, C 6 -C 10 aryl substituted by one or more R 2-1-1 , C 1 -C 6 alkyl substituted by one or more R 2-1-2 or 5-12 membered heteroaryl substituted by one or more R 2-1-3 , wherein in the 5-12 membered heteroaryl, the heteroatom is selected from 1,2 or 3 of N, O and S, and the heteroatom number is 1,2, 3 or 4; Each R 2-1-1 is independently C 1 -C 6 alkyl substituted with one or more halogens; each R 2-1-2 is independently C 6 -C 10 aryl; Each R 2-1-3 is independently halogen; Each R 2-2 is independently C 3 -C 10 monocyclic cycloalkyl substituted by one or more R 2-2-1 ; Each R 2-2-1 is independently C 6 -C 10 aryl; Each R 2-3 is independently oxo (=O), -C (=O) OR a 、-C(＝O)R a , A C 6 -C 10 aryl group, a 5-12 membered heteroaryl group or a C 6 -C 10 aryl group substituted with one or more R 2-3-1 groups, wherein in the 5-12 membered heteroaryl group, the heteroatoms are selected from 1,2 or 3 of N, O and S, and the number of the heteroatoms is 1,2,3 or 4; Each R 2-3-1 is independently halogen OR a ; Each R 2-4 is independently halogen, OR a , Or CN, preferably halogen; Each R a is independently C 1 -C 6 alkyl or H; Scheme b: q is 0 or 1; R 3 is H, -OH or halogen; Y 1 is CR Y1 ; Y 2 is CR Y2 ; y 3 is CR Y3 ; R Y1 and R Y2 are each independently H; R Y3 is H or halogen; Q is CR Q1 R Q2 ; r Q1 and R Q2 are independently H; R X is H; Each R 1 is independently C 1 -C 6 alkyl; The number of hetero atoms in the 3-12 membered heterocycloalkylene is independently 1,2 or 3, the hetero atoms are independently selected from 1,2 or 3 of N, O and S, and at least one hetero atom is N; R 2 is C 5 -C 10 polycyclic cycloalkyl, 3-12 membered heterocycloalkyl, C 3 -C 10 monocyclic cycloalkyl substituted by one or more R 2-1 , C 1 -C 6 alkyl substituted by one or more R 2-2 , 3-12 membered heterocycloalkyl substituted by one or more R 2-3 or C 5 -C 10 polycyclic cycloalkyl substituted by one or more R 2-4 , wherein in the 3-12 membered heterocycloalkyl, the heteroatoms are each independently selected from 1,2 or 3 of N, O and S, and the number of heteroatoms is each independently 1,2 or 3; Each R 2-1 is independently C 6 -C 10 aryl or C 1 -C 6 alkyl substituted with one or more R 2-1-2 ; each R 2-1-2 is independently C 6 -C 10 aryl; Each R 2-2 is independently C 3 -C 10 monocyclic cycloalkyl substituted by one or more R 2-2-1 ; Each R 2-2-1 is independently C 6 -C 10 aryl; Each R 2-3 is independently-C (=O) OR a 、-C(＝O)R a , A C 6 -C 10 aryl group, a 5-12 membered heteroaryl group or a C 6 -C 10 aryl group substituted with one or more R 2-3-1 groups, wherein in the 5-12 membered heteroaryl group, the heteroatoms are selected from 1,2 or 3 of N, O and S, and the number of the heteroatoms is 1,2,3 or 4; Each R 2-3-1 is independently halogen; Each R 2-4 is independently halogen, OR a , Or CN, preferably halogen; Each R a is independently C 1 -C 6 alkyl or H; Scheme c: in scheme c, the compound shown in formula II is a compound shown in formula II-1 as follows: Wherein, the R 3 is H, -OH or halogen, preferably H; y 3 is CR Y3 ; R Y3 is independently H or halogen; R X is H; The ring A is 4-7 membered monocyclic heterocycloalkylene or 7-10 membered bridged heterocycloalkylene, the number of heteroatoms in the 4-7 membered monocyclic heterocycloalkylene and 7-10 membered bridged heterocycloalkylene is 1 or 2 respectively, the number of heteroatoms in the 4-7 membered monocyclic heterocycloalkylene and 7-10 membered bridged heterocycloalkylene is N, O respectively, the number of heteroatoms in the 4-7 membered monocyclic heterocycloalkylene is preferably 4-7 membered monocyclic heterocycloalkyl, the number of heteroatoms in the 4-7 membered monocyclic heterocycloalkylene is 1 or 2 respectively, the number of heteroatoms in the 4-7 membered monocyclic heterocycloalkylene is N, O respectively, the number of heteroatoms in the 7-10 membered monocyclic heterocycloalkylene is 2 respectively, and the number of heteroatoms in the 4-7 membered monocyclic heterocycloalkylene is N; R 2 is C 5 -C 10 polycyclocycloalkyl, 3-12 membered heterocycloalkyl, C 3 -C 10 monocyclocycloalkyl substituted by one or more R 2-1 , C 1 -C 6 alkyl substituted by one or more R 2-2 , 3-12 membered heterocycloalkyl substituted by one or more R 2-3 or C 5 -C 10 polycyclocycloalkyl substituted by one or more R 2-4 , wherein the 3-12 membered heterocycloalkyl is independently selected from 1, 2 or 3 of N, O and S, the number of heteroatoms is independently 1, 2 or 3, preferably C 5 -C 10 polycyclocycloalkyl, 7-10 membered spirocycloalkyl, 7-10 membered bridged heterocycloalkyl or C 5 -C 10 polycyclocycloalkyl substituted by one or more R 2-4 , the heteroatoms in the 7-10 membered spirocycloalkyl and 7-10 membered bridged heterocycloalkyl are independently selected from 1 or 2 of N, O and S, the number of heteroatoms is independently 1 or 2 of heteroatoms; Each R 2-1 is independently C 6 -C 10 aryl or C 1 -C 6 alkyl substituted with one or more R 2-1-2 ; each R 2-1-2 is independently C 6 -C 10 aryl; each R 2-4 is independently halogen; Each R 2-2 is independently C 3 -C 10 monocyclic cycloalkyl substituted by one or more R 2-2-1 ; Each R 2-2-1 is independently C 6 -C 10 aryl; Each R 2-3 is independently C 6 -C 10 aryl OR-C (=o) OR a ; Each R a is independently C 1 -C 6 alkyl.
  5. A compound of formula II or a pharmaceutically acceptable salt thereof as claimed in claim 4 which satisfies one or more of the following conditions: (1) R 2 is (2) Is that (3) Is that (4) R x is H.
  6. The compound of formula II or a pharmaceutically acceptable salt thereof according to claim 5, wherein the compound of formula II is any one of the following structures: Preferably, the method comprises the steps of, IKZF2 degradation (Hibit) DC 50 is not less than 50nM, maximum degradation rate at 1. Mu.M is not less than 50%, or IKZF2 degradation (Hibit) DC 50 is less than 50nM, maximum degradation rate at 1. Mu.M is not less than 50%.
  7. The compound of formula II or a pharmaceutically acceptable salt thereof according to claim 5, wherein the pharmaceutically acceptable salt of the compound of formula II is any one of the following structures: Preferably, the method comprises the steps of, IKZF2 degradation (WB) DC 50 is <100nM, maximum degradation rate at 1. Mu.M is not less than 75%, or IKZF2 degradation (Hibit) DC 50 is <50nM, maximum degradation rate at 1. Mu.M is not less than 50%.
  8. A compound of formula III or a pharmaceutically acceptable salt thereof, or a compound of formula IV: Wherein Q, R 1 , ring A, R 3 、Y 1 、Y 2 、Y 3 , Q and R X are as defined in any one of claims 1 to 7; R 5 is H, -C (=o) -OR 5-1 OR C 3 -C 10 monocyclic cycloalkyl substituted with one OR more R 5-2 OR; R 5-1 is C 1 -C 6 alkyl; each R 5-2 is independently C 6 -C 10 aryl or C 6 -C 10 aryl substituted with one or more R 2-5-1 ; each R 2-5-1 is independently C 1 -C 6 alkyl substituted with one or more halogens; R 6 is oxo (=O) or Preferably, R 5 is H,
  9. The compound of formula III or a pharmaceutically acceptable salt thereof, or the compound of formula IV, according to claim 8, which satisfies one or both of the following conditions: (1) The compound shown in the formula III has any one of the following structures: (2) The compound shown in the formula IV has any one of the following structures:
  10. A compound as shown below:
  11. A pharmaceutical composition comprising a substance Z which is a compound of formula II as described in any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant.
  12. Use of a substance Z, which is a compound of formula II as defined in any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 11 for the manufacture of a protein degrading agent targeting IKZF2 or a medicament for the treatment and/or prophylaxis of a disorder associated with IKZF 2.
  13. The use according to claim 12 wherein the disorder associated with IKZF2 is one or more of a tumour, a disorder caused by infection with a virus, bacteria or other pathogen, or a disorder associated with aging in humans, preferably one or more of head and neck cancer, cervical cancer, gall bladder cancer, bile duct cancer, gastric cancer, colorectal cancer, rectal cancer, hepatocellular carcinoma, glioma, renal cancer, neuroblastoma, sarcoma, lung cancer, ovarian cancer, bladder cancer, pancreatic cancer, melanoma, breast cancer, triple negative breast cancer, nasopharyngeal carcinoma, bone cancer, brain cancer, spinal cord cancer, melanoma, meningioma, prostate cancer, uterine cancer, lymphoma and myeloid leukaemia.
  14. Use of a substance Z or a pharmaceutical composition according to claim 11 for the preparation of a medicament, said substance Z being a compound according to formula II according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof; The medicament is preferably for the treatment of one or more of a tumour, a disease caused by infection with a virus, bacteria or other pathogen, or a disease associated with aging of the human body, preferably one or more of head and neck cancer, cervical cancer, gall bladder cancer, bile duct cancer, gastric cancer, colorectal cancer, rectal cancer, hepatocellular carcinoma, glioma, renal cancer, neuroblastoma, sarcoma, lung cancer, ovarian cancer, bladder cancer, pancreatic cancer, melanoma, breast cancer, triple negative breast cancer, nasopharyngeal cancer, bone cancer, brain cancer, spinal cord cancer, melanoma, meningioma, prostate cancer, uterine cancer, lymphoma and myeloid leukaemia.

Description

Heterocyclic compound, composition and application thereof The present application claims priority from China patent application 2023112756095 with the application date 2023/9/28. The present application incorporates the entirety of the above-mentioned chinese patent application. Technical Field The invention relates to a heterocyclic compound, a composition and application thereof. Background The Ikaros protein family comprises Ikaros (Ikzf), helios (Ikzf 2), aiolos (Ikzf 3), eos (Ikzf 4), and Pegasus (Ikzf 5), are hematopoietic-specific transcription factors involved in regulating lymphocyte development. IKZF2 forms homo-or heterodimers with other Ikaros family members and is thought to play a major role in hematopoietic development. IKZF2 is highly expressed at mRNA and protein levels in regulatory T cells (Tregs), and the expression of FoxP3 is affected by a promoter that binds to the primary transcriptional regulator of regulatory T cells, foxP3, thereby affecting the development and function of regulatory T cells. The function of IKZF2 in regulatory T cells is to maintain the suppressive properties of regulatory T cells. Knocking out IKZF2 of regulatory T cells in mice results in activated regulatory T cells losing their inhibitory properties and expressing effector T cytokines to exert effector T cell functions. Regulatory T cells play a critical role in maintaining autoimmune tolerance, but accumulation of regulatory T cells within the Tumor Microenvironment (TME) will suppress anti-tumor immunity. Targeting regulatory T cells is an important direction in the development of tumor immunomodulators, and a number of clinical drug candidates have entered the clinical development stage and made clinical progress, such as anti-TIGIT antibodies, anti-CCR4 antibodies, anti-CTL4 antibodies against Tregs, for enhancing anti-tumor immune responses. Immunomodulatory Drugs (IMiD) such as pomalidomide and lenalidomide induce degradation of IKZF1 and IKZF3 transcription factors. The IMiD does not bind to IKZF1/3 itself, by binding to CRBN E3 ligase, forms a protein-small molecule complex and creates a complex surface. These newly formed complex surfaces recruit new substrates. IKZF1 and 3 were recruited to the IMiD-bound CRBN and then labeled with ubiquitin, resulting in degradation of IKZF1 and 3 by the proteasome. Other proteins such as GSPT and IKZF2 can also be degraded by similar methods. The protein degradation agent targeting the IKZF2 can inhibit the activity of Treg cells by degrading the IKZF2, thereby inhibiting the immune suppression effect mediated by the Treg cells and increasing the anti-tumor activity of tumor immunotherapy. Therefore, the research and development of the protein degradation agent targeting Helios (IKZF 2) has potential clinical application value. Disclosure of Invention The invention provides a heterocyclic compound, a composition and application thereof. The compound has one or more of the following advantages of novel structure, high efficiency and high selectivity for degrading IKZF2, inhibiting and regulating the function of T cells, and great clinical development value when applied to treating tumors or diseases. The invention provides a compound shown as a formula II or pharmaceutically acceptable salt thereof; wherein q is 0,1,2 or 3; R 3 is H, -OH or halogen; Y 1 is CR Y1 or N; Y 2 is CR Y2 or N; y 3 is CR Y3 or N; R Y1、RY2 and R Y3 are each independently H, NR aRb、ORa or halogen; Q is CR Q1RQ2; R Q1 and R Q2 are independently H, deuterium or C 1-C6 alkyl; R X is H or deuterium; Each R 1 is independently C 1-C6 alkyl or halogen; The ring A is 3-12 membered heterocycloalkylene or 3-12 membered heterocycloalkenylene, wherein in the 3-12 membered heterocycloalkylene and 3-12 membered heterocycloalkenylene, the number of hetero atoms is 1,2 or 3 respectively and independently, the hetero atoms are 1,2 or 3 respectively and independently selected from N, O and S, and at least one hetero atom is N; R 2 is C 3-C10 monocyclic cycloalkyl, C 5-C10 polycyclic cycloalkyl, 3-12 membered heterocycloalkyl, C 3-C10 monocyclic cycloalkyl substituted by one or more R 2-1, C 1-C6 alkyl substituted by one or more R 2-2, 3-12 membered heterocycloalkyl substituted by one or more R 2-3 or C 5-C10 polycyclic cycloalkyl substituted by one or more R 2-4, wherein in the 3-12 membered heterocycloalkyl, the heteroatoms are independently selected from 1, 2 or 3 of N, O and S, and the number of heteroatoms is independently 1, 2 or 3; Each R 2-1 is independently OR a, -CONRaRb、CN, C 3-C10 cycloalkyl, 3-12 membered heterocycloalkyl, halogen, C 6-C10 aryl, 5-12 membered heteroaryl, C 1-C6 alkyl, C 6-C10 aryl substituted with one or more R 2-1-1, C 1-C6 alkyl substituted with one or more R 2-1-2, or 5-12 membered heteroaryl substituted with one or more R 2-1-3, wherein in the 5-12 membered heteroaryl, the heteroatoms are each independently selected from 1, 2, or 3 of N, O and S, the number of heteroatoms is