EP-4735425-A1 - COMPOUNDS

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 (1)

1. CLAIMS 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, C2-6 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 C6-16 alkyleneheteroaryl, said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 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 C6-16 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 C6-16 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 ; R 2 is independently selected from hydrogen, C1-6haloalkyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 alkyleneheteroaryl, said C1-6haloalkyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 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 C6-16 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 ; alternatively R 1 and R 2 are combined with the atoms to which they are attached to 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 C 3-8 heterocycloalkyl being further optionally substituted with one or more substituents independently 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, C2-6alkenyl, C2-6 haloalkenyl, C2-6 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 independently 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, C2-6 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 ; each R 4 is independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-7 cycloalkyl, and C3-7 heterocycloalkylncluding 1 or 2 ring heteromoieties selected from O, S, S(O), SO2, N and NR 5 , said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 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, CO2R 5 , C(O)N(R 5 )2, OR 5 , N(R 5 )2, NO2, SR 5 and SO2R 5 , said C3-C7 cycloalkyl and C3-7 heterocycloalkyl each being further optionally substituted with one or more substituents independently 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, S(O), SO2, N and NR 5 ; each R 5 is independently selected from hydrogen, C 1 - 6 alkyl, C 2 - 6 alkenyl, C 2 - 6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C5-10 heterocycloalkyl, C6-12 aryl and C5-10 heteroaryl, said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C5-10 heterocycloalkyl, C6-12 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, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, 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, S(O), SO2, N, NH and NCH3; L is selected from C1-4 alkylene, C2-C4 alkenylene and C2-C4 alkynylene; Z 1 is CR 8 or N; Z 2 is CR 9 or N; Z 3 is CR 10 or N; Z 4 is CR 11 or N; R 6 is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkyleneP(O)(OR 12 )2, C(O)R 12 , CO2R 12 , C(O)N(R 12 )2, S(O)R 12 and SO2R 12 , C3- 6 cycloalkyl, C6-9 alkylenecycloalkyl, C3-6 heterocyclyl, C6-9 alkyleneheterocycloalkyl, C4- 7 heterocyclyl, C7-10 alkyneneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 alkyleneheteroaryl, said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-9 alkylenecycloalkyl, C3-6 heterocyclyl, C6-9 alkyleneheterocycloalkyl, C4-7 heterocyclyl, C7-10 alkyneneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 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 12 , C(O)N(R 12 )2, OR 12 , N(R 12 )2, NO2, SR 12 and SO2R 12 , said C3-6 cycloalkyl, C6-9 alkylenecycloalkyl, C3-6 heterocyclyl, C6- 9 alkyleneheterocycloalkyl, C4-7 heterocyclyl, C7-10 alkyneneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 alkyleneheteroaryl each being further optionally substituted with one or more substituents independently 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 12 ; each R 12 is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 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 C6-16 alkyleneheteroaryl, said C1-6 alkyl, C2-6 alkenyl, C2-6 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 C6-16 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)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, 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, S(O), SO2, N, NH and NCH3; 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, C2-6 alkenyl, C2-C6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C1-6 alkylamine, C1-6 alkoxy, C1-6 haloalkoxy, CO2R 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, OC1-6alkyleneP(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, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, C4-16 alkyleneheteroaryl, said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-C6 haloalkenyl, C2-6 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, C 7-18 alkylenearyl, C 5-10 heteroaryl, and C 4-16 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 independently selected from (O), C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-6cycloalkyl 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, C2-6 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 C6-16 alkyleneheteroaryl, said C1-6 alkyl, C2-6 alkenyl, C2-6 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 C6-16 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)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, 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, S(O), SO2, N, NH and NCH3; alternatively, when Z 1 is CR 8 and Z 2 is CR 9 , or when Z 2 is CR 9 and Z 3 is CR 10 , or when Z 3 is CR 10 and Z 4 is CR 11 , then R 8 and R 9 , or R 9 and R 10 , or R 10 and R 11 may be combined with the atoms to which they are each attached to form a C4-8 cycloalkyl, C5-8 heterocycloalkyl, C6-12 aryl, or C5-10 heteroaryl, said C4-8 cycloalkyl, C5-8 heterocycloalkyl, C6-12 aryl, and C5-10 heteroaryl each being further optionally substituted with one or more substituents independently selected from halogen, (O), CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2R 14 , C(O)N(R 14 )2, OR 14 , N(R 14 )2, NO2, SR 14 , SO2R 14 , C1-6 alkyl, C1-6 haloalkyl, C 2 - 6 alkenyl, C 2 - 6 haloalkenyl, C 2 - 6 alkynyl, C 2 - 6 haloalkynyl, C 3 - 6 cycloalkyl and C3-6 heterocycloalkyl including 1 or 2 ring heteromoieties selected from O, S, N, S(O), SO2 and NR 14 ; each R 14 is independently selected from hydrogen, C1-6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C3-10 heterocycloalkyl, C6-12 aryl and C5-10 heteroaryl; said C1-6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C3- 10 heterocycloalkyl, C6-12 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, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NO2, NHCH3, SH, SCH3, SO2CH3, SOCH3, 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, S(O), SO2, N, NH and NCH3; and wherein the compound of formula (I) is not one of the following: 2. The compound of claim 1, or a pharmaceutically acceptable salt, solvate,automer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein Z 1 , Z 2 , Z 3 and Z 4 are defined by embodiments 1-5: E N 1 2 3 4 5 3. The compound of claim 2, or a pharmaceutically acceptable salt, solvate,automer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein Z 1 , Z 2 , Z 3 and Z 4 are according to embodiment 4. 4. The compound of any one of claims 1-3, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein 1 or 2 of R 8 , R 9 , R 10 and R 11 when present are each independently selectedrom halogen, C 1-6 alkyl, C 1-6 haloalkyl and OR 13 wherein R 13 is selected from C 1-6 alkyl and C1-6 haloalkyl, and the other of R 8 R 9 , R 10 and R 11 are each hydrogen. 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 two of R 8 , R 9 , R 10 and R 11 are other than hydrogen. 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 6 is H. 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 9 and R 10 are both other than hydrogen. 8. The compound of claim 7, or a pharmaceutically acceptable salt, solvate,automer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 8 and R 11 are hydrogen. 9. The compound of any one of claims 1-8, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 1 and R 2 are each independently selected from C1-4 alkyl. 10. The compound of any one of claims 1-8, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein, R 1 and R 2 are combined with the atoms to which they are attached to form a C4-8 heterocycloalkyl that does not include additional ring heteromoieties. 11. The compound of claim 1, or a pharmaceutically acceptable salt, solvate,automer, 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 theollowing: , , , , , , , , , , , , , , 12. The compound of any one of claims 1-11, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein R 3 is hydrogen. 13. The compound of any one of claims 1-12, or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, wherein L is methylene. 14. The compound of claim 1, selected from: A-73 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof. 15. A medicament comprising a compound of any one of claims 1-14 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof. 16. A pharmaceutical composition comprising a compound of any one of claims 1-14 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, and a pharmaceutically acceptable excipient. 17. A method of treating a disease, disorder or condition by activation of a serotonin eceptor, the method comprising administering to a subject in need thereof 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, C2-6 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 C6-16 alkyleneheteroaryl, said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 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 C6-16 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, C4-C14 alkyleneheterocycloalkyl, C3- C8 heterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 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 ; R 2 is independently selected from hydrogen, C1-6haloalkyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 alkyleneheteroaryl, said C1-6haloalkyl, C3-8 cycloalkyl, C4-14 alkylenecycloalkyl, C3-C8 heterocycloalkyl, C4-C14 alkyleneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 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 C6-16 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 ; alternatively R 1 and R 2 are combined with the atoms to which they are attached to 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 independently 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 , C 1-6 alkyl, C 1-6 haloalkyl, C 2 - 6 alkenyl, 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), 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 independently 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, C2-6 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 ; each R 4 is independently selected from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C3-7 cycloalkyl, and C3-7 heterocycloalkylncluding 1 or 2 ring heteromoieties selected from O, S, S(O), SO2, N and NR 5 , said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, C2-6 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, CO2R 5 , C(O)N(R 5 )2, OR 5 , N(R 5 )2, NO2, SR 5 and SO2R 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, 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, S(O), SO2, N and NR 5 ; each R 5 is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C5-10 heterocycloalkyl, C6-12 aryl and C5-10 heteroaryl, said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-8 cycloalkyl, C5-10 heterocycloalkyl, C6-12 aryl and C5-10 heteroaryl each being optionally substituted with one or more substituents independently selected from halogen, CN, C 1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, 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, S(O), SO2, N, NH and NCH3; L is selected from C1-4 alkylene, C2-C4 alkenylene and C2-C4 alkynylene; Z 1 is CR 8 or N; Z 2 is CR 9 or N; Z 3 is CR 10 or N; Z 4 is CR 11 or N; R 6 is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkyleneP(O)(OR 12 )2, C(O)R 12 , CO2R 12 , C(O)N(R 12 )2, S(O)R 12 and SO2R 12 , C3- 6 cycloalkyl, C6-9 alkylenecycloalkyl, C3-6 heterocyclyl, C6-9 alkyleneheterocycloalkyl, C4- 7 heterocyclyl, C7-10 alkyneneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 alkyleneheteroaryl, said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C6-9 alkylenecycloalkyl, C3-6 heterocyclyl, C6-9 alkyleneheterocycloalkyl, C4-7 heterocyclyl, C7-10 alkyneneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 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 12 , C(O)N(R 12 )2, OR 12 , N(R 12 )2, NO2, SR 12 and SO2R 12 , said C3-6 cycloalkyl, C6-9 alkylenecycloalkyl, C3-6 heterocyclyl, C6- 9 alkyleneheterocycloalkyl, C4-7 heterocyclyl, C7-10 alkyneneheterocycloalkyl, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, and C6-16 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), SO 2 and NR 12 ; each R 12 is independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 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 C6-16 alkyleneheteroaryl, said C1-6 alkyl, C2-6 alkenyl, C2-6 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 C6-16 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)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, 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, S(O), SO2, N, NH and NCH3; 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, C2-6 alkenyl, C2-C6 haloalkenyl, C2-6 alkynyl, C2-6 haloalkynyl, C1-6 alkylamine, C1-6 alkoxy, C1-6 haloalkoxy, CO2R 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, OC1-6alkyleneP(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, C6-12 aryl, C7-18 alkylenearyl, C5-10 heteroaryl, C4-16 alkyleneheteroaryl, said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-C6 haloalkenyl, C2-6 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, C 6-12 aryl, C 7-18 alkylenearyl, C 5-10 heteroaryl, and C 4-16 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, C3-6cycloalkyl 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, C2-6 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 C6-16 alkyleneheteroaryl, said C1-6 alkyl, C2-6 alkenyl, C2-6 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 C6-16 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)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, 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, S(O), SO2, N, NH and NCH3; alternatively, when Z 1 is CR 8 and Z 2 is CR 9 , or when Z 2 is CR 9 and Z 3 is CR 10 , or when Z 3 is CR 10 and Z 4 is CR 11 , then R 8 and R 9 , or R 9 and R 10 , or R 10 and R 11 are combined with the atoms to which they are each attached to form a C4-8 cycloalkyl, C5-8 heterocycloalkyl, C6-12 aryl, or C5-10 heteroaryl, said C4-8 cycloalkyl, C5-8 heterocycloalkyl, C6-12 aryl, and C5-10 heteroaryl each being further optionally substituted with one or more substituents independently selected from halogen, (O), CN, C1-8 alkoxy, C1-8 alkylamino, C1-8 alkylsulfonyl, CO2R 14 , C(O)N(R 14 )2, OR 14 , N(R 14 )2, NO2, SR 14 , SO2R 14 , 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 14 ; each R 14 is independently selected from hydrogen, C1-6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C 1 -C 6 haloalkyl, C 3 -C 7 cycloalkyl, C 3 - 10 heterocycloalkyl, C 6-12 aryl and C 5-10 heteroaryl; said C1-6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C7 cycloalkyl, C3- 10 heterocycloalkyl, C6-12 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, CO2H, CO2CH3, C(O)NH2, C(O)N(CH3)2, C(O)NHCH3, OH, NH2, N(CH3)2, NHCH3, NO2, SH, SCH3, SO2CH3, SOCH3, 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, S(O), SO2, N, NH and NCH3. 19. A method of treating a mental illness, comprising administering to a subject in need thereof an effective amount of a compound defined in claim 18 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof,. 20. A method of treating a central nervous system (CNS) disease, disorder or condition and/or a neurological disease, disorder or condition, the method comprising administering to a subject in need thereof an effective amount of a compound defined in claim 18 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof. 21. A method for increasing neuronal plasticity and/or increasing dendritic spine density, the method comprising contacting a neuronal cell with a compound as definedn claim 18 or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof. 22. The method of any one of claims 17-21, wherein the compound of formula (I), or a pharmaceutically acceptable salt, solvate, tautomer, N-oxide, stereoisomer, metabolite, polymorph or prodrug thereof, is a compound of any one of claims 1-14, optionally administered in the form of the medicament of claim 15 or the pharmaceutical composition of claim 16.

Description

Compounds This application claims priority to Australian provisional application no.2023902054 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 tohe 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 ofeading 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,hese therapeutics provide limited benefit when compared to a placebo. Additionally,hese therapeutics can result in a wide range of side effects including loss of libido,nsomnia, 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. n 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 changesn perception, visual hallucinations, and distorted sense of space, time, and self. Many patients report spiritual or “mystical” experiences which have profound and lastingmpact on the patients’ mood and behaviour. Psilocybin has shown promise in morehan 50 clinical trials for neuropsychiatric indications, including numerous anxiety disorders, obsessive-compulsive disorder, anorexia nervosa, alcohol dependence, andobacco addiction. Psilocybin and other psychedelic compounds such as N,N- dimethyltryptamine (DMT) and 5-methoxy-N,N-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 recentlyed to increased awareness of the potential for psychedelic drugs as breakthroughherapies 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 broadmplementation. 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 eceptors (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. n view of the foregoing there is an ongoing need to develop new compounds which may