Search

EP-4735441-A1 - PYRROLOPYRIDINE COMPOUNDS FOR THE TREATMENT OF MENTAL ILLNESSES

EP4735441A1EP 4735441 A1EP4735441 A1EP 4735441A1EP-4735441-A1

Abstract

The present disclosure relates generally to compounds, their methods of synthesis, and their use in the treatment of mental illness or central nervous system disorders.

Inventors

  • BANISTER, Samuel
  • JORGENSEN, WILLIAM
  • Tan, Jinlong
  • WHISH, Lachlan

Assignees

  • Psylo Pty Ltd

Dates

Publication Date
20260506
Application Date
20240628

Claims (20)

  1. 1. A compound of formula (I): or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 1 is independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-6 haloalkynyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl, said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-6 haloalkynyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4- C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl each being optionally substituted with one or more substituents independently selected from halogen, CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2R 4 , C(O)N(R 4 ) 2 , OR 4 , N(R 4 ) 2 , NO2, SR 4 and SO2R 4 , said C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl each being further optionally substituted with one or more substituent independently selected from (O), C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, N, S(O), SO2 and NR 4 ; R 2 is independently selected from hydrogen, Ci ehaloalkyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl, said Ci ehaloalkyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl each being optionally substituted with one or more substituents independently selected from halogen, CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2R 4 , C(O)N(R 4 ) 2 , OR 4 , N(R 4 ) 2 , NO2, SR 4 and SO2R 4 , said C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl each being further optionally substituted with one or more substituents independently selected from (O), C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, N, S(O), SO2 and NR 4 ; alternatively R 1 and R 2 together with the atoms to which they are attached form a C3-8 heterocycloalkyl including 0, 1 or 2 additional ring heteromoieties selected from O, S, S(O), SO2, N and NR 4 , said C3-8 heterocycloalkyl being further optionally substituted with one or more substituents selected from halogen, (O), CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2R 4 , C(O)N(R 4 ) 2 , OR 4 , N(R 4 ) 2 , NO2, SR 4 , SO2R 4 , C1-6 alkyl, C1-6 haloalkyl, C2-ealkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-6 haloalkynyl, C1-8 alkylamino, C1-8 alkylsulfonyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, N, S(O), SO2 and NR 4 ; R 3 is selected from hydrogen, C1-6 alkyl, C3-8 cycloalkyl, or C4-14 alkylenecycloalkyl; alternatively R 3 and one of R 1 and R 2 are combined with the atoms to which they are attached to form a C3-12 heterocycloalkyl, said C3-12 heterocycloalkyl being further optionally substituted with one or more substituents selected from halogen, (O), CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2R 4 , C(O)N(R 4 ) 2 , OR 4 , N(R 4 ) 2 , NO 2 , SR 4 , SO 2 R 4 , C1-6 alkyl, C1-6 haloalkyl, C 2 -6 alkenyl, C 2 -6 haloalkenyl, C 2 -6 alkynyl, C 2 -6 haloalkynyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, N, S(O), SO 2 and NR 4 ; each R 4 is independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C 2 -6 alkenyl, C 2 -6 haloalkenyl, C 2 -6 alkynyl, C 2 -6 haloalkynyl, C3-7 cycloalkyl, and C3-7 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, S(O), SO 2 , N and NR 5 , said C1-6 alkyl, C1-6 haloalkyl, C 2 -6 alkenyl, C 2 -6 haloalkenyl, C 2 -6 alkynyl, C 2 -6 haloalkynyl, C3-7 cycloalkyl and C3-7 heterocycloalkyl each being optionally substituted with one or more substituents independently selected from halogen, CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO 2 R 5 , C(O)N(R 5 ) 2 , OR 5 , N(R 5 ) 2 , NO 2 , SR 5 and SO 2 R 5 , said C3-C7 cycloalkyl and C3-7 heterocycloalkyl each being further optionally substituted with one or more substituents independently selected from (O), C1-6 alkyl, C1-6 haloalkyl, C 2 -6 alkenyl, C 2 -6 haloalkenyl, C 2 -6 alkynyl, C 2 -6 haloalkynyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, S(O), SO 2 , N and NR 5 ; each R 5 is independently selected from hydrogen, C1-6 alkyl, C 2 -6 alkenyl, C 2 -6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C5-10 heterocycloalkyl, Ce-i 2 aryl and C5-10 heteroaryl, said C1-6 alkyl, C 2 -6 alkenyl, C 2 -6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C5-10 heterocycloalkyl, Ce-i 2 aryl and C5-10 heteroaryl each being optionally substituted with one or more substituents independently selected from halogen, CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO 2 H, CO 2 CH3, C(O)NH 2 , C(O)N(CH 3 ) 2 , C(O)NHCH 3 , OH, NH 2 , N(CH 3 ) 2 , NHCH3, NO 2 , SH, SCH3, SO 2 CH3, SOCH3, C1-6 alkyl, C1-6 haloalkyl, C 2 -6 alkenyl, C 2 -6 haloalkenyl, C 2 -6 alkynyl, C 2 -6 haloalkynyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, S(O), SO 2 , N, NH and NCH3; R 7 , R 8 , R 9 , R 10 and R 11 are each independently selected from hydrogen, halogen, CN, OR 13 , N(R 13 ) 2 , SR 13 , C1-6 alkyl, C1-6 haloalkyl, C 2-6 alkenyl, C 2 -C 6 haloalkenyl, C 2-6 alkynyl, C 2 -6 haloalkynyl, C1-6 alkylamine, C1-6 alkoxy, C1-6 haloalkoxy, CO 2 R 13 , C(O)R 13 , C(O)N(R 13 ) 2 , C(O)C(O)N(R 13 ) 2 , OC(O)R 13 , OC(O)OR 13 , OC(O)N(R 13 ) 2 , OS(O)R 13 , OS(O)N(R 13 ) 2 , OSO2R 13 , OP(O)(OR 13 ) 2 , OCi- 6 alkyleneP(O)(OR 13 ) 2 , S(O)R 13 , S(O)N(R 13 ) 2 , SO2R 13 , N(R 13 ) 2 , N(R 13 )C(O)R 13 , N(R 13 )C(O)OR 13 , N(R 13 )C(O)N(R 13 ) 2 , NO2, C3-8 cycloalkyl, C3-14 alkylenecycloalkyl, C3-10 heterocycloalkyl, C4-16 alkyleneheterocycloalkyl, Ce-i2 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, C4-16 alkyleneheteroaryl, said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-C6 haloalkenyl, C2-e alkynyl, C2-6 haloalkynyl, C1-6 alkylamine, C1-6 alkoxy, C1-6 haloalkoxy, C3-8 cycloalkyl, C3-14 alkylenecycloalkyl, C3-10 heterocycloalkyl, C4-16 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C4-16 alkyleneheteroaryl being optionally substituted with one or more substituents independently selected from halogen, CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2R 13 , C(O)N(R 13 ) 2 , OR 13 , N(R 13 ) 2 , NO2, SR 13 and SO2R 13 , said C3-8 cycloalkyl, C3-14 alkylenecycloalkyl, C3-10 heterocycloalkyl, C4-16 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C4-16 alkyleneheteroaryl each being further optionally substituted with one or more substituents selected from (O), C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-6 haloalkynyl, Cs-ecycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoeities selected from O, S, S(O), SO2, N, and NR 13 ; each R 13 is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-10 heterocycloalkyl, C4-16 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl, said C1-6 alkyl, C2-6 alkenyl, C2-e alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-10 heterocycloalkyl, C4-16 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl each being optionally substituted with one or more substituents independently selected from halogen, CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2H, CO2CH3, C(O)NH 2 , C(O)N(CH 3 ) 2 , C(O)NHCH 3 , OH, NH 2 , N(CH 3 ) 2 , NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, S(O), SO2, N, NH and NCH3.
  2. 2. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 9 is independently selected from halogen, CN, -OH, C1-6 haloalkyl, C1-6 alkoxy, and C1-6 haloalkoxy, said C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, is optionally substituted with one or more substituents independently selected from halogen, CN, C1-8 alkoxy, C1-8 alkylamino, Ci-8 alkylsulfonyl, CO2R 13 , C(O)N(R 13 ) 2 , OR 13 , N(R 13 ) 2 , NO 2 , SR 13 and SO 2 R 13 ,
  3. 3. The compound of claim 2, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 9 is selected from halo, CN, -OH, Ci-4alkoxy, Ci-4haloalkoxy and Ci-4haloalkyl.
  4. 4. The compound of claim 3, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 9 is selected from fluoro, chloro, bromo, CN, -OH, methoxy, trifluoromethoxy and trifluoromethyl.
  5. 5. The compound of any one of claims 1 to 4, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 7 is H, R 8 is H and R 10 is H, and the compound is provided by formula (II):
  6. 6. The compound of any one of claims 1-5, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 1 is independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C 2 -6 alkenyl, C 2 -6 haloalkenyl, C 2 -e alkynyl, C 2 -6 haloalkynyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, Ce-i 2 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl, said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-e alkynyl, C2-6 haloalkynyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4- C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl each being optionally substituted with one or more substituents independently selected from halogen, CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2R 4 , C(O)N(R 4 ) 2 , OR 4 , N(R 4 ) 2 , NO2, SR 4 and SO2R 4 , said C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl each being further optionally substituted with one or more substituents independently selected from (O), C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, N, S(O), SO2 and NR 4 .
  7. 7. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 1 is independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, said C1-6 alkyl, C1-6 haloalkyl, each being optionally substituted with one or more substituents independently selected from halogen, CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2R 4 , C(O)N(R 4 ) 2 , OR 4 , N(R 4 ) 2 , NO2, SR 4 and SO2R 4 .
  8. 8. The compound of any one of claims 1-7, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 2 is independently selected from C1-6 haloalkyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl, said C1-6 haloalkyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, Cs- 10 heteroaryl, and Ce-16 alkyleneheteroaryl each being optionally substituted with one or more substituents independently selected from halogen, CN, C1-8 alkoxy, Ci-8 alkylamino, Ci-8 alkylsulfonyl, CO2R 4 , C(O)N(R 4 ) 2 , OR 4 , N(R 4 ) 2 , NO 2 , SR 4 and SO 2 R 4 , said C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, Ce-i 2 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and Ce-16 alkyleneheteroaryl each being further optionally substituted with one or more substituents independently selected from (O), C1-6 alkyl, C1-6 haloalkyl, C 2 -6 alkenyl, C 2 -6 haloalkenyl, C 2 -6 alkynyl, C 2 -6 haloalkynyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, N, S(O), SO 2 and NR 4 .
  9. 9. The compound of any one of claims 1-6, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 1 and R 2 together with the atoms to which they are attached form a C3-8 heterocycloalkyl including 0, 1 or 2 additional ring heteromoieties selected from O, S, S(O), SO 2 , N and NR 4 , said C3-8 heterocycloalkyl being further optionally substituted with one or more substituents selected from halogen, (O), CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO 2 R 4 , C(O)N(R 4 ) 2 , OR 4 , N(R 4 ) 2 , NO 2 , SR 4 , SO 2 R 4 , C1-6 alkyl, C1-6 haloalkyl, C 2 -6alkenyl, C 2 -6 haloalkenyl, C 2 -6 alkynyl, C 2 -6 haloalkynyl, C1-8 alkylamino, C1-8 alkylsulfonyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, N, S(O), SO 2 and NR 4 .
  10. 10. The compound of claim 9, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 1 and R 2 together form a C4-8 heterocycloalkyl including 0 or 1 additional ring heteromoieties selected from O, S, S(O), SO 2 , N and NR 4 , wherein the C4- sheterocycloalkyl is optionally substituted with one or more substituents selected from halogen, C1-8 alkoxy, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, N, S(O), SO 2 and NR 4 .
  11. 11. The compound of claim 9 or 10, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 1 and R 2 together with the nitrogen atom to which they are attached form a C4-8 heterocycloalkyl that does not include additional ring heteromoieties.
  12. 12. The compound of anyone of claims 9-11 , or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 1 and R 2 together with the nitrogen atom to which they are attached form a bicyclic Ce-8 heterocycloalkyl.
  13. 13. The compound of any one of claims 1-5, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein: R 1 is independently selected from hydrogen, optionally substituted C1-6 alkyl, optionally substituted C1-6 haloalkyl, optionally substituted C3-8 cycloalkyl, optionally substituted C4- 14 alkylenecycloalkyl, optionally substituted C3-C8 heterocycloalkyl, optionally substituted C4-C14 alkyleneheterocycloalkyl, optionally substituted C6-12 aryl, optionally substituted C7-18 alkylenearyl, optionally substituted C5-10 heteroaryl, and optionally substituted Ce-16 alkyleneheteroaryl, and R 2 is independently selected from optionally substituted C3-8 cycloalkyl, optionally substituted C4-14 alkylenecycloalkyl, optionally substituted C3-C8 heterocycloalkyl, optionally substituted C4-C14 alkyleneheterocycloalkyl, optionally substituted C6-12 aryl, optionally substituted C7-18 alkylenearyl, optionally substituted C5-10 heteroaryl, and optionally substituted Ce-16 alkyleneheteroaryl, or alternatively R 1 and R 2 together with the atoms to which they are attached form an optionally substituted C3-8 heterocycloalkyl including 0, 1 or 2 additional ring heteromoieties selected from O, S, S(O), SO2, N and NR 4 .
  14. 14. The compound of any one of claims 1-5, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 1 and R 2 , together with the nitrogen to which they are attached, form any one of the following:
  15. 15. The compound of any one of claims 1-13, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 3 is hydrogen.
  16. 16. The compound of claim 1, selected from: or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof.
  17. 17. A medicament comprising a compound of any one of claims 1-16 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof.
  18. 18. A pharmaceutical composition comprising a compound of any one of claims 1-16 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, and a pharmaceutically acceptable excipient.
  19. 19. A method of treating a disease, disorder or condition by activation of a serotonin receptor, the method comprising administering to a subject in need thereof a compound of any one of claims 1-16 or a pharmaceutically acceptable salt, solvate, tautomer, N- oxide, stereoisomer, metabolite, polymorph or prodrug thereof, the medicament of claim 17 or the pharmaceutical composition of claim 18.
  20. 20. A method of treating a mental illness, comprising administering to a subject in need thereof an effective amount of a compound of any one of claims 1-16 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, the medicament of claim 17 or the pharmaceutical composition of claim 18.

Description

Compounds This application claims priority to Australian provisional application no. 2023902053 (filed on 28 June 2023), the entire contents of which is incorporated herein by reference. Field of the invention The present disclosure relates generally to novel compounds, their methods of synthesis, and their use in the treatment of mental illness or central nervous system disorders. Background of the invention Mental illness covers many neuropsychiatric disorders which cause enormous burden to the lives of their sufferers. Diagnoses such as treatment resistant depression, major depressive disorder, eating disorders, substance abuse disorders, post-traumatic stress disorder, obsessive compulsive disorder, attention deficit disorders, schizophrenia, and others can cause such devastating symptoms that many sufferers lose the capability of leading a normal life. A variety of serotonergic drugs such as antidepressants, serotonin reuptake inhibitors, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and others are commercially available to treat mental illnesses. Unfortunately, in many indications, these therapeutics provide limited benefit when compared to a placebo. Additionally, these therapeutics can result in a wide range of side effects including loss of libido, insomnia, fatigue, weight gain, and others. In spite of their limited efficacy, these drugs continue to be used to treat neuropsychiatric conditions as well as a broad range of auxiliary medical indications. There have been limited advances in new treatment options since many of these drugs were released, and the pharmaceutical industry has come under increased financial pressure to de-emphasise neuroscience programmes entirely. The unmet need for more efficacious mental health treatment is on the rise, and the global COVID-19 pandemic is likely to increase disease burden around the world. In the 1950s and 1960s, the use of psychedelic drugs to treat various mental illnesses was extensively explored, and these substances showed promise as treatments for many diseases of the central nervous system (CNS). Following decades of prohibition, scientific research into the application of psychedelics as treatments for mental illnesses has been gaining momentum. The serotonergic psychedelic agent psilocybin has been designated a Breakthrough Therapy by the FDA for the treatment of major depressive disorder (2019) and treatment-resistant depression (2018). Psilocybin is the prodrug compound produced by many species of mushrooms known collectively as psilocybin mushrooms or “magic mushrooms”. Psilocybin is rapidly metabolized to the bioactive compound psilocin, which produces a state of altered consciousness including changes in perception, visual hallucinations, and distorted sense of space, time, and self. Many patients report spiritual or “mystical” experiences which have profound and lasting impact on the patients’ mood and behaviour. Psilocybin has shown promise in more than 50 clinical trials for neuropsychiatric indications, including numerous anxiety disorders, obsessive-compulsive disorder, anorexia nervosa, alcohol dependence, and tobacco addiction. Psilocybin and other psychedelic compounds such as /V,/V- dimethyltryptamine (DMT) and 5-methoxy-/V,/V-dimethyltryptamine (5-MeO-DMT) have both immediate and persistent effects on mental state, with the latter extending far beyond the duration of action, possibly as a result of their ability to incite increased neuroplasticity, promote neural outgrowth, and increase spine density of the synaptic neurons in the brain. To date, psilocybin remains classified as a controlled substance and/or drug of abuse in most countries under national drug laws. However, clinical investigations have recently led to increased awareness of the potential for psychedelic drugs as breakthrough therapies to treat CNS diseases of enormous unmet medical need. Despite its therapeutic potential, psilocybin and other psychedelics remain scheduled drugs of abuse in most countries and the commercial path to market for these drugs as medicines is uncertain. As an adjunct to psychotherapy, the long duration of action of psilocybin and LSD make treatment sessions costly and impractical for broad implementation. In spite of a long history of safe human use, several adverse events have been reported in clinical trials, and it is possible that these may be attributed to signalling bias at 5-HT2A (the primary target) or off-target activity at, for example, 5- HT2B receptors (a cardiac liability antitarget) or 5-HT1A (an anxiolytic target) or 5-HT2C receptors (a disease-relevant target for obesity and some genetic epilepsies, for example). Naturally-occurring psychedelics provide important lead structures for a new generation of neurotherapeutic agents with novel mechanisms of action and/or superior clinical efficacy to currently available neuropsychiatric medications. In view of the foregoing there is an ongoing need t