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US-12624041-B2 - Heterocyclic compound and use thereof

US12624041B2US 12624041 B2US12624041 B2US 12624041B2US-12624041-B2

Abstract

Disclosed is a heterocyclic compound as represented by formula (I), a tautomer thereof, or a pharmaceutically acceptable salt thereof. The compound has better inhibitory activity on TRPC5, has good metabolic stability in liver micro-particles, and has good clinical pharmacokinetic properties.

Inventors

  • Jinping Li
  • Xiaodan Guo
  • Feng Zhou
  • Jun Lou
  • Li Liu
  • Xiaoya Chen
  • YIHAN ZHANG
  • Yongkai CHEN
  • Chaodong Wang

Assignees

  • WUHAN LL SCIENCE AND TECHNOLOGY DEVELOPMENT CO., LTD.

Dates

Publication Date
20260512
Application Date
20210623
Priority Date
20200703

Claims (20)

  1. 1 . A heterocyclic compound represented by formula I, a tautomer thereof, a pharmaceutically acceptable salt thereof, a solvate thereof or a solvate of the pharmaceutically acceptable salt thereof: wherein, m is 1; A is —(CR 1 R 2 )—; R 1 is independently hydrogen, halogen, R 1-1 , R 1-2 substituted by one, two or more R 1-3 , —(C═O)NHR 14 , —NH(C═O)R 1-5 , —(C═O)OR 1-6 , —S(═O) 2 R 1-7 , or —S(═O)R 1-8 ; R 1-1 and R 1-2 are independently amino, C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, C 6 -C 20 aryl-C 1 -C 40 alkyl, 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S —C 1 -C 40 alkyl; R 1-3 , R 1-4 , R 1-5 , R 1-6 , R 1-7 and R 1-8 are independently —CN, halogen, —OH, —NH 2 , —COOH, —NO 2 , —S(═O) 2 CH 3 , —C(═O)NHCH 2 CH 3 , oxo (═O), —NHC(═O)R 1-3-4 , —C(═O)OR 1-3-5 , R 1-3-1 , or R 1-3-2 substituted by one, two or more R 1-3-3 ; R 1-3-1 and R 1-3-2 are independently C 1 -C 40 alkyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 1-3-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; R 1-3-4 is independently hydrogen, R 1-3-4-1 , or R 1-3-4-2 substituted by one, two or more R 1-3-4-3 ; R 1-3-4-1 and R 1-3-4-2 are independently C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 1-3-4-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; R 1-3-5 is independently hydrogen, R 1-3-5-1 , or R 1-3-5-2 substituted by one, two or more R 1-3-5-3 ; R 1-3-5-1 and R 1-3-5-2 are independently C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 1-3-5-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; R 2 is independently hydrogen, halogen, R 2-1 , R 2-2 substituted by one, two or more R 2-3 , —(C═O)NHR 2-4 , —NH(C═O)R 2-5 , —(C═O)OR 2-6 , —S(═O) 2 R 2-7 , or —S(═O)R 2-8 ; R 2-1 and R 2-2 are independently amino, C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, C 6 -C 20 aryl-C 1 -C 40 alkyl, 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S —C 1 -C 40 alkyl; R 2-3 , R 2-4 , R 2-5 , R 2-6 , R 2-7 and R 2-8 are independently —CN, halogen, —OH, —NH 2 , —COOH, —NO 2 , —S(═O) 2 CH 3 , —C(═O)NHCH 2 CH 3 , oxo (═O), —NHC(═O)R 2-3-4 , —C(═O)OR 2-3-5 , R 2-3-1 , or R 2-3-2 substituted by one, two or more R 2-3-3 ; R 2-3-1 and R 2-3-2 are independently C 1 -C 40 alkyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 2-3-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; R 2-3-4 is independently hydrogen, R 2-3-4-1 , or R 2-3-4-2 substituted by one, two or more R 2-3-4-3 ; R 2-3-4-1 and R 2-3-4-2 are independently C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 2-3-4-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; R 2-3-5 is independently hydrogen, R 2-3-5-1 , or R 2-3-5-2 substituted by one, two or more R 2-3-5-3 ; R 2-3-5-1 and R 2-3-5-2 are independently C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 2-3-5-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; n is 2; G is —(CR 3 R 4 )—; R 3 is independently hydrogen, halogen, R 3-1 , R 3-2 substituted by one, two or more R 3-3 , —(C═O)NHR 3-4 , —NH(C═O)R 3-5 , —(C═O)OR 3-6 , —S(═O) 2 R 3-7 , or —S(═O)R 3-8 ; R 3-1 and R 3-2 are independently amino, C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, C 6 -C 20 aryl-C 1 -C 40 alkyl, 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S —C 1 -C 40 alkyl; R 3-3 , R 3-4 , R 3-5 , R 3-6 , R 3-7 and R 3-8 are independently —CN, halogen, —OH, —NH 2 , —COOH, —NO 2 , —S(═O) 2 CH 3 , —C(═O)NHCH 2 CH 3 , oxo (═O), —NHC(═O)R 3-3-4 , —C(═O)OR 3-3-5 , R 3-3-1 , or R 3-3-2 substituted by one, two or more R 3-3-3 ; R 3-3-1 and R 3-3-2 are independently C 1 -C 40 alkyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 3-3-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; R 3-3-4 is independently hydrogen, R 3-3-4-1 , or R 3-3-4-2 substituted by one, two or more R 3-3-4-3 ; R 3-3-4-1 and R 3-3-4-2 are independently C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 3-3-4-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; R 3-3-5 is independently hydrogen, R 3-3-5-1 , or R 3-3-5-2 substituted by one, two or more R 3-3-5-3 ; R 3-3-5-1 and R 3-3-5-2 are independently C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 3-3-5-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; R 4 is independently hydrogen, halogen, R 4-1 , R 4-2 substituted by one, two or more R 4-3 , —(C═O)NHR 4-4 , —NH(C═O)R 4-5 , —(C═O)OR 4-6 , —S(═O) 2 R 4-7 , or —S(═O)R 4-8 ; R 4-1 and R 4-2 are independently amino, C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, C 6 -C 20 aryl-C 1 -C 40 alkyl, 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S —C 1 -C 40 alkyl; R 4-3 , R 4-4 , R 4-5 , R 4-6 , R 4-7 and R 4-8 are independently —CN, halogen, —OH, —NH 2 , —COOH, —NO 2 , —S(═O) 2 CH 3 , —C(═O)NHCH 2 CH 3 , oxo (═O), —NHC(═O)R 4-3-4 , —C(═O)OR 4-3-5 , R 4-3-1 , or R 4-3-2 substituted by one, two or more R 4-3-3 ; R 4-3-1 and R 4-3-2 are independently C 1 -C 40 alkyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 4-3-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; R 4-3-4 is independently hydrogen, R 4-3-4-1 , or R 4-3-4-2 substituted by one, two or more R 4-3-4-3 ; R 4-3-4-1 and R 4-3-4-2 are independently C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 1 -C 40 alkoxy, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 4-3-4-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; R 4-3-5 is independently hydrogen, R 4-3-5-1 , or R 4-3-5-2 substituted by one, two or more R 4-3-5-3 ; R 4-3-5-1 and R 4-3-5-2 are independently C 1 -C 40 alkyl, C 2 -C 40 alkenyl, C 2 -C 40 alkynyl, C 3 -C 20 cycloalkyl, 3- to 20-membered heterocycloalkyl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S, C 6 -C 20 aryl, or 5- to 20-membered heteroaryl with 1, 2 or 3 heteroatoms selected from one or more of N, O and S; R 4-3-5-3 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; X is N, Z is CR 6 ; R 6 is hydrogen, halogen, amino, C 1 -C 4 alkyl substituted by one or more R 6-2 , C 1 -C 4 alkoxy or —C(═O)—NH—R 6-1 ; R 6-1 is C 1 -C 4 alkyl; R 6-2 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; Y is —O—, —S—, —NR 8 —, —CH 2 —, —C(═O)— or —S(═O)—; R 8 is hydrogen, C 1 -C 4 alkyl substituted by one or more R 8-2 , C 1 -C 4 alkoxy or —C(═O)—NH—R 8-1 ; R 8-1 is C 1 -C 4 alkyl; R 8-2 is independently —CN, halogen, —OH, —NH 2 , oxo (═O), —S(═O) 2 CH 3 , C 1 -C 40 alkyl, C 1 -C 40 alkyl substituted by one or more halogens, C 1 -C 40 alkoxy, or C 1 -C 40 alkoxy substituted by one or more halogens; p is 1, 2 or 3; R 5 is independently cyano, halogen, —OH, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —NR 9 R 10 , C 3 -C 6 cycloalkyl, or C 1 -C 4 alkyl substituted by one or more halogens; R 9 and R 10 are independently H or C 1 -C 4 alkyl.
  2. 2 . The heterocyclic compound represented by formula I according to claim 1 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein, R 1 is independently hydrogen or R 1-1 ; R 1-1 is C 1 -C 40 alkyl; or, R 2 is hydrogen; or, R 3 is independently hydrogen, R 3-1 , or R 3-2 substituted by one, two or more R 3-3 ; R 3-1 and R 3-2 are independently C 1 -C 40 alkyl; R 3-3 is —OH; or, R 4 is hydrogen; or, X is N and Z is CR 6 ; R 6 is hydrogen, halogen or —C(═O)—NH—R 6-1 ; R 6-1 is C 1 -C 4 alkyl; or, Y is —NR 8 —, —CH 2 —, —C(═O)— or —S(═O)—; R 8 is hydrogen; or, p is 1 or 2; or, R 5 is independently cyano, halogen, C 1 -C 4 alkoxy, —NR 9 R 10 , C 3 -C 6 cycloalkyl, or C 1 -C 4 alkyl substituted by one or more halogens; R 9 and R 10 are independently H, methyl or ethyl.
  3. 3 . The heterocyclic compound represented by formula I according to claim 2 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein, R 1 is hydrogen; or, R 3 is hydrogen; or, X is N and Z is CR 6 ; R 6 is hydrogen; or, Y is —CH 2 — or —C(═O)—; or, R 5 is independently cyano, halogen, or C 1 -C 4 alkyl substituted by one or more halogens.
  4. 4 . The heterocyclic compound represented by formula I according to claim 1 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein, R 1 is independently hydrogen or R 1-1 ; R 1-1 is independently methyl or ethyl; or, R 3 is independently hydrogen, R 3-1 or R 3-2 substituted by one, two or more R 3-3 ; R 3-1 and R 3-2 are independently methyl or ethyl; R 3-3 is —OH; or, Y is —O—, —S—, —NR 8 —, —CH 2 —, —C(═O)— or —S(═O)—; R 8 is hydrogen; or, R 5 is independently cyano, halogen, —OH, C 1 -C 4 alkoxy, —NR 9 R 10 , C 3 -C 6 cycloalkyl, or C 1 -C 4 alkyl substituted by one or more halogens; R 9 and R 10 are independently C 1 -C 4 alkyl.
  5. 5 . The heterocyclic compound represented by formula I according to claim 1 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein, the heterocyclic compound is as described in any one of the following schemes: scheme 1: m is 1; A is —(CR 1 R 2 )—; R 1 is independently hydrogen or R 1-1 ; R 1-1 is independently C 1 -C 40 alkyl; R 2 is hydrogen; n is 2; G is —(CR 3 R 4 )—; R 3 is independently hydrogen, R 3-1 , or R 3-2 substituted by one, two or more R 3-3 ; R 3-1 and R 3-2 are independently C 1 -C 40 alkyl; R 3-3 is —OH; R 4 is hydrogen; X is N and Z is CR 6 ; R 6 is hydrogen, halogen or —C(═O)—NH—R 6-1 ; R 6-1 is C 1 -C 4 alkyl; Y is —NR 8 — or —CH 2 —; R 8 is hydrogen; p is 1 or 2; R 5 is independently halogen, or C 1 -C 4 alkyl substituted by one or more halogens; scheme 2: m is 1; A is —(CR 1 R 2 )—; R 1 is hydrogen; R 2 is hydrogen; n is 2; G is —(CR 3 R 4 )—; R 3 is hydrogen; R 4 is hydrogen; X is N and Z is CR 6 ; R 6 is hydrogen, halogen or —C(═O)—NH—R 6-1 ; R 6-1 is C 1 -C 4 alkyl; Y is —NR 8 — or —CH 2 —; R 8 is hydrogen; p is 1 or 2; R 5 is independently halogen, or C 1 -C 4 alkyl substituted by one or more halogens; scheme 3: m is 1; A is —(CR 1 R 2 )—; R 1 is hydrogen; R 2 is hydrogen; n is 2; G is —(CR 3 R 4 )—; R 3 is hydrogen; R 4 is hydrogen; X is N and Z is CR 6 ; R 6 is hydrogen; Y is —CH 2 —; p is 1 or 2; R 5 is independently halogen, or C 1 -C 4 alkyl substituted by one or more halogens; scheme 4: m is 1; A is —(CR 1 R 2 )—; R 1 is independently hydrogen or R 1-1 ; R 1-1 is independently C 1 -C 40 alkyl; R 2 is hydrogen; n is 2; G is —(CR 3 R 4 )—; R 3 is independently hydrogen, R 3-1 , or R 3-2 substituted by one, two or more R 3-3 ; R 3-1 and R 3-2 are independently C 1 -C 40 alkyl; R 3-3 is —OH; R 4 is hydrogen; X is N and Z is CR 6 ; R 6 is hydrogen, halogen or —C(═O)—NH—R 6-1 ; R 6-1 is C 1 -C 4 alkyl; Y is —NR 8 —, —CH 2 —, —C(═O)— or —S(═O)—; R 8 is hydrogen; p is 1 or 2; R 5 is independently cyano, halogen, —OH, C 1 -C 4 alkoxy, —NR 9 R 10 , C 3 -C 6 cycloalkyl, or C 1 -C 4 alkyl substituted by one or more halogens; R 9 and R 10 are independently C 1 -C 4 alkyl; scheme 5: m is 1; A is —(CR 1 R 2 )—; R 1 is independently hydrogen or R 1-1 ; R 1-1 is independently methyl or ethyl; R 2 is hydrogen; n is 2; G is —(CR 3 R 4 )—; R 3 is independently hydrogen, R 3-1 , or R 3-2 substituted by one, two or more R 3-3 ; R 3-1 and R 3-2 are independently methyl or ethyl; R 3-3 is —OH; R 4 is hydrogen; X is N and Z is CR 6 ; R 6 is hydrogen, halogen or —C(═O)—NH—R 6-1 ; R 6-1 is methyl or ethyl; Y is —NR 8 —, —CH 2 —, —C(═O)— or —S(═O)—; R 8 is hydrogen; p is 1 or 2; R 5 is independently cyano, halogen, —OH, methoxy, ethoxy, —NR 9 R 10 , cyclopropyl or methyl substituted by one or more halogens; R 9 and R 10 are independently methyl or ethyl; scheme 6: m is 1; A is —(CR 1 R 2 )—; R 1 is hydrogen; R 2 is hydrogen; n is 2; G is —(CR 3 R 4 )—; R 3 is hydrogen; R 4 is hydrogen; X is N and Z is CR 6 ; R 6 is hydrogen; Y is —CH 2 —, —C(═O)— or —S(═O)—; p is 1 or 2; R 5 is independently halogen, cyano, —OH, or C 1 -C 4 alkyl substituted by one or more halogens; scheme 7: m is 1; A is —(CR 1 R 2 )—; R 1 is hydrogen; R 2 is hydrogen; n is 2; G is —(CR 3 R 4 )—; R 3 is hydrogen; R 4 is hydrogen; X is N and Z is CR 6 ; R 6 is hydrogen; Y is —CH 2 —, —C(═O)— or —S(═O)—; p is 1 or 2; R 5 is independently halogen, cyano, —OH, or C 1 -C 4 alkyl substituted by one or more halogens; when p is 1, R 5 is C 1 -C 4 alkyl substituted by one or more halogens; when p is 2, the C 1 -C 4 alkyl substituted by one or more halogens is C 1 -C 4 alkyl substituted by 3 halogens; scheme 9: the structure of the heterocyclic compound represented by formula I is represented by formula IV or formula V: scheme 10: the structure of the heterocyclic compound represented by formula I is represented by formula VI or formula VII: scheme 11: m is 1; A is —(CR 1 R 2 )—; R 1 is independently hydrogen or R 1-1 ; R 1-1 is C 1 -C 40 alkyl; R 2 is hydrogen; n is 2; G is —(CR 3 R 4 )—; R 3 is independently hydrogen, R 3-1 , or R 3-2 substituted by one, two or more R 3-3 ; R 3-1 and R 3-2 are independently C 1 -C 40 alkyl; R 3-3 is —OH; R 4 is hydrogen; X is N, Z is CR 6 ; R 6 is hydrogen, halogen or —C(═O)—NH—R 6-1 ; R 6-1 is C 1 -C 4 alkyl; Y is —O—, —S—, —NR 8 —, —CH 2 —, —C(═O)— or —S(═O)—; R 8 is hydrogen; p is 1 or 2; R 5 is independently cyano, halogen, —OH, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, —NR 9 R 10 , C 3 -C 6 cycloalkyl, or C 1 -C 4 alkyl substituted by one or more halogens; R 9 and R 10 are independently C 1 -C 4 alkyl; scheme 12: m is 1; A is —(CR 1 R 2 )—; R 1 is independently hydrogen or R 1-1 ; R 1-1 is independently methyl or ethyl; R 2 is hydrogen; n is 2; G is —(CR 3 R 4 )—; R 3 is independently hydrogen, R 3-1 , or R 3-2 substituted by one, two or more R 3-3 ; R 3-1 and R 3-2 are independently methyl or ethyl; R 3-3 is —OH; R 4 is hydrogen; X is N and Z is CR 6 ; R 6 is hydrogen, halogen or —C(═O)—NH—R 6-1 ; R 6-1 is methyl or ethyl; Y is —O—, —S—, —NR 8 —, —CH 2 —, —C(═O)— or —S(═O)—; R 8 is hydrogen; p is 1 or 2; R 5 is independently cyano, halogen, —OH, methoxy, ethoxy, —NR 9 R 10 , cyclopropyl, methyl, difluoromethyl or trifluoromethyl; R 9 and R 10 are independently methyl or ethyl; scheme 13: m is 1; A is —(CR 1 R 2 )—; R 1 is hydrogen; R 2 is hydrogen; n is 2; G is —(CR 3 R 4 )—; R 3 is hydrogen; R 4 is hydrogen; X is N and Z is CR 6 ; R 6 is hydrogen; Y is —CH 2 — or —C(═O)—; p is 1 or 2; R 5 is independently halogen, cyano, or methyl substituted by one or more halogens; when p is 2, the R 5 is located at the ortho and para positions of the Y, and the methyl substituted by one or more halogens is methyl substituted by 3 halogens; when Y is —CH 2 — and p is 1, R 5 is methyl substituted by one or more halogens.
  6. 6 . The heterocyclic compound represented by formula I according to claim 1 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein, when A is independently —(CR 1 R 2 )—, the carbon atoms connected to R 1 and R 2 are carbon atoms of R-configuration or carbon atoms of S-configuration; or, when R 1-1 is C 1 -C 40 alkyl, the C 1 -C 40 alkyl is C 1 -C 4 alkyl; or, when G is —(CR 3 R 4 )—, wherein, the carbon atoms connected to R 3 and R 4 are carbon atoms of R-configuration or carbon atoms of S-configuration; or, when R 3-1 is C 1 -C 40 alkyl, the C 1 -C 40 alkyl is C 1 -C 4 alkyl; or, when R 3-2 is C 1 -C 40 alkyl, the C 1 -C 40 alkyl is C 1 -C 4 alkyl; or, when R 6 is halogen, the halogen is fluorine, chlorine or bromine; or, when R 6-1 is C 1 -C 4 alkyl, the C 1 -C 4 alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl; or, the R 5 is independently located at the ortho, meta or para position of the Y; or, when R 5 is independently halogen, the halogen is fluorine, chlorine or bromine; or, when R 5 is independently C 1 -C 4 alkyl substituted by one or more halogens, the number of the more halogens is 2 or 3; or, when R 5 is independently C 1 -C 4 alkyl substituted by one or more halogens, the halogen is fluorine, chlorine or bromine; or, when R 5 is independently C 1 -C 4 alkyl substituted by one or more halogens, the C 1 -C 4 alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.
  7. 7 . The heterocyclic compound represented by formula I according to claim 6 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein, when R 1-1 is C 1 -C 40 alkyl, the C 1 -C 40 alkyl is methyl or ethyl; or, when R 3-1 is C 1 -C 40 alkyl, the C 1 -C 40 alkyl is methyl or ethyl; or, when R 3-2 is C 1 -C 40 alkyl, the C 1 -C 40 alkyl is methyl or ethyl; or, when R 6 is halogen, the halogen is bromine; or, when R 6-1 is C 1 -C 4 alkyl, the C 1 -C 4 alkyl is methyl; or, when p is 1, the R 5 is located at the ortho position of the Y; or, when p is 2, the R 5 is located at the ortho or para position of the Y; or, when R 5 is independently halogen, the halogen is fluorine or chlorine; or, when R 5 is independently C 1 -C 4 alkyl substituted by more halogens, the C 1 -C 4 alkyl substituted by more halogens is difluoromethyl or trifluoromethyl.
  8. 8 . The heterocyclic compound represented by formula I according to claim 1 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein, when p is 2, the R 5 is independently located at the ortho or para position of the Y, or is located at the ortho or meta position of the Y;
  9. 9 . The heterocyclic compound represented by formula I according to claim 8 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein,
  10. 10 . The heterocyclic compound represented by formula I according to claim 7 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein, when R 3 is independently R 3-2 substituted by one R 3-3 , the R 3-2 substituted by one R 3-3 is hydroxymethyl; or, the is 2-trifluoromethylphenyl, 2-trifluoromethyl-4-fluorophenyl, 2-difluoromethyl-4-fluorophenyl, 2,4-difluorophenyl or 2-chloro-4-fluorophenyl,
  11. 11 . The heterocyclic compound represented by formula I according to claim 10 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein, the is 2-trifluoromethylphenyl, 2-trifluoromethyl-4-fluorophenyl, 2-difluoromethyl-4-fluorophenyl, 2,4-difluorophenyl, 2-chloro-4-fluorophenyl
  12. 12 . The heterocyclic compound represented by formula I according to claim 1 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvate of the pharmaceutically acceptable salt thereof, wherein, the heterocyclic compound represented by formula I is any one of the following compounds:
  13. 13 . A pharmaceutical composition, comprising substance Y and pharmaceutical excipients, the substance Y is the heterocyclic compound represented by formula I according to claim 1 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvent thereof or the solvent of the pharmaceutically acceptable salt thereof.
  14. 14 . A method for inhibiting TRPC5 in a subject in need thereof, comprising: administering an effective amount of substance Y to the subject, the substance Y is the heterocyclic compound represented by formula I according to claim 1 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvent of the pharmaceutically acceptable salt thereof.
  15. 15 . A method for treating a TRPC5-mediated disease in a subject in need thereof, comprising: administering an effective amount of substance Y to the subject, the substance Y is the heterocyclic compound represented by formula I according to claim 1 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvate thereof or the solvent of the pharmaceutically acceptable salt thereof.
  16. 16 . The method according to claim 15 , the TRPC5-mediated disease is psychiatric condition, neurological condition, neurodegenerative condition or nephropathy; the psychiatric condition, neurological condition or neurodegenerative condition can be selected from: borderline personality disorder, depression, post-traumatic stress disorder, panic disorder, agoraphobia, social phobia, generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, separation anxiety amnesia, aphasia, brain injury, brain tumor, chronic fatigue syndrome, Creutzfeldt-Jakob disease, dissociative amnesia, fugue amnesia, learning disorder, sleeping disorder, multiple personality disorder, pain, post-traumatic stress disorder, schizophrenia, sports injury, stroke, Wernicke-Korsakoff Syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis or epilepsy; the nephropathy can be focal segmental glomerulosclerosis, minimal change nephropathy or diabetic nephropathy.
  17. 17 . A method for treating psychiatric condition, neurological condition, neurodegenerative condition or nephropathy in a subject in need thereof, comprising: administering an effective amount of substance Y to the subject, the substance Y is the heterocyclic compound represented by formula I according to claim 1 , the tautomer thereof, the pharmaceutically acceptable salt thereof, the solvent thereof, or the solvent of the pharmaceutically acceptable salt thereof.
  18. 18 . The method according to claim 17 , the psychiatric condition, neurological condition or neurodegenerative condition is selected from: borderline personality disorder, depression, post-traumatic stress disorder, panic disorder, agoraphobia, social phobia, generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, separation anxiety amnesia, aphasia, brain injury, brain tumor, chronic fatigue syndrome, Creutzfeldt-Jakob disease, dissociative amnesia, fugue amnesia, learning disorder, sleeping disorder, multiple personality disorder, pain, post-traumatic stress disorder, schizophrenia, sports injury, stroke, Wernicke-Korsakoff Syndrome, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis or epilepsy; or, the nephropathy is focal segmental glomerulosclerosis, minimal change nephropathy or diabetic nephropathy.
  19. 19 . The method according to claim 16 , wherein the depression is selected from major depression, major depressive disorder, psychiatric depression, dysthymia and postpartum depression, and bipolar disorder.
  20. 20 . The method according to claim 18 , wherein the depression is selected from major depression, major depressive disorder, psychiatric depression, dysthymia and postpartum depression, and bipolar disorder.

Description

The present application claims the right of the priorities of Chinese patent application 2020106363080 filed on Jul. 3, 2020 and Chinese patent application 2020114601432 filed on Dec. 11, 2020. The contents of the above Chinese patent application are incorporated herein by reference in its entireties. TECHNICAL FIELD The present disclosure related to a heterocyclic compound and a use thereof. BACKGROUND There are various ion channel proteins to regulate the ion flow through the cell membrane. The proper expression and function of ion channel protein are important for the maintenance of cell function and intracellular communication. Many diseases are caused by abnormal regulation of membrane potential or abnormal calcium treatment. Given the central importance of ion channels in the regulation of membrane potential and ion flow in cells, the identification of agents that can promote or inhibit specific ion channels is of great interest as research tools and as possible therapeutic agents. TRPC (Transient Receptor Potential Canonical) is one of the most important subfamilies in the TRP superfamily, including TRPC1-7, wherein, TRPC2 is a pseudogene and is not expressed in humans. According to amino acid sequence homology and structural characteristics, TRPCs can be divided into two subclasses: TRPC1, 4, 5 are classified as a subclass, and TRPC3, 6, 7 are classified as a subclass. According to the activation mode, functional TRPC can be divided into store-operated calcium channel and receptor-operated calcium channel. Both modes of activation of TRPC channels behave as nonspecific cation channels that mediate sodium and calcium influx and potassium efflux. Cation channels (such as transient receptor potential (TRP) cation channel subfamily C, member 5 (TRP5)) regulate the flow of calcium and sodium ions through cell membranes. The influx of sodium and calcium leads to depolarization of cells. This increases the likelihood that voltage-gated ion channels will reach the threshold required for activation. Thus, activation of non-selective cation channels increases electrical excitability and increases the frequency of voltage-dependent events. Voltage-dependent events include, but are not limited to, neuronal action potential, cardiac action potential, smooth muscle contraction, cardiac muscle contraction and skeletal muscle contraction. Calcium influx caused by activation of non-selective cation channels (such as TRPC5) also alters intracellular free calcium concentration. Calcium is a ubiquitous second messenger molecule in cells, and the change in intracellular calcium level has a profound effect on signal transduction and gene expression. Therefore, activation of non-selective cation channels (such as TRPC5) can lead to changes in gene expression and cell phenotype. Gene expression events include, but are not limited to, the production of mRNA encoding cell surface receptors, ion channels and kinases. These changes in gene expression can lead to the hyperexcitability of this cell. Homomeric TRPC5 ion channels are signaling-gated, Ca2+-permeable channels expressed primarily in neurons. TRPC5 forms homomeric multi-subunit structures (such as tetramers (i.e., TRPC5 homomultimers)) and heteromeric multi-subunit structures (such as tetramers (such as TRPC5-TRPC1 heteromultimers)). Unless otherwise specified, when the term TRPC5 is used herein (for example, when identifying modulators of TRPC5, such as TRPC5 antagonists), the term TRPC5 is generally used to include one or both of TRPC5 homomultimers or heteropolymers (such as TRPC5-TPRC1 or TRPC5-TRPC4 heteropolymers). Examples of TRPC5 in the literature include the following: Nature., Jan. 3, 2008; 451(7174): 69-72; Mol Pharmacol. January 2008; 73(1): 42-9; J Biol Chem. Nov. 16, 2007; 282(46): 33868-78; Biochem Biophys Res Commun. Jan. 11, 2008; 365(2): 239-45; J Biol Chem. Nov. 3, 2006; 281(44): 33487-96; Eur J Pharmacol. Mar. 14, 2005; 510(3): 217-22; J Biol Chem. Feb. 24, 2006; 281(8): 4977-82; Biochem Soc Trans. February 2007; 35 (Pt 1): 101-4; Handb Exp Pharmacol. 2007; (179): 109-23; J Biol Chem. Mar. 25, 2005; 280(12): 10997-1006; J Physiol. Jan. 15, 2006; 570 (Pt 2): 219-35; and Nat Neurosci. (2003) 6:837-45. Modulating the function of the TRPC5 protein provides methods for modulating calcium homeostasis, sodium homeostasis, membrane polarization, and/or intracellular calcium level, and the compound that can modulate TRPC5 function are useful in many ways, including but not limited to maintaining calcium homeostasis, regulating intracellular calcium level, modulation of membrane polarization, and treatment or prevention of diseases, disorders or conditions associated with calcium and/or sodium homeostasis or dyshomeostasis. The compound that inhibits TRPC5 containing ion channels is, for example, suitable for treating diseases by regulating the activity of transient receptor potential cation channel subfamily C, member 5 (TRPC5) which can be in the form of