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KR-20260062950-A - 3-(2-(dimethylamino)ethyl)-1H-indole-4-yl derivative

KR20260062950AKR 20260062950 AKR20260062950 AKR 20260062950AKR-20260062950-A

Abstract

The present invention provides a compound of formula (I), a compound selected from any of the compounds in Table 1, Table 2, and Table 3 , or a pharmaceutically acceptable salt or deuterated form thereof, wherein R1 , R2 , R3 , and R4 are defined herein. The present invention also provides a pharmaceutical composition comprising a compound of formula (I), a compound selected from any of the compounds in Table 1, Table 2, and Table 3, or a pharmaceutically acceptable salt or deuterated form thereof, and, for example, a method of using a compound of formula (I) or a pharmaceutically acceptable salt or deuterated form thereof in the treatment of a 5- HT2A receptor-associated disease or disorder.

Inventors

  • 모피 존 리차드
  • 베이커 토마스 매튜
  • 브라운 앤드루 윌리엄

Assignees

  • 컴퍼스 패쓰파인더 리미티드

Dates

Publication Date
20260507
Application Date
20240823
Priority Date
20230825

Claims (20)

  1. Compound of chemical formula (I) or as a pharmaceutically acceptable salt or deuterated form thereof, Among the above formulas R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; R 1 is defined according to i, ii, iii, or iv : i. R1 is -OR8 , where R8 is an alkynyl substituted with NR5R6 , or -( CH2CH2O ) m -alkyl, where m is 1, 2, 3, 5 , or 6; R 5 and R 6 are independently H, alkyl, C(=O)alkyl, alkylene-aryl, or S(O) 2alkyl ; ii. R1 is -R9A , where R9A is -C( RA ) 2NR5R6 , -C ( RA ) 2 -O-alkyl, -C( RA ) 2 -O-cycloalkyl, cycloalkyl substituted with -Oalkyl, heterocyclyl substituted with -C(= O )Oalkyl, alkenylene-aryl substituted with 1 to 4 R7A , alkenylene-heteroaryl substituted with 0 to 4 R7A , aryl substituted with NR5R6 , or a pentatomic heteroaryl substituted with 1 to 4 groups selected from alkyl, OH, halogen, haloalkyl, Oalkyl, or O-haloalkyl; Each R A is independently H, halo, unsubstituted alkyl, or alkylene-OH, or Two R A groups form a cycloalkylene or heterocyclylene together with the carbons to which they are connected, and However, at least one R A is not H; R5 and R6 are independently H, alkyl, or or C(=O)alkyl, where the alkyl is optionally substituted with NH₂ , NH(alkyl), N(alkyl) ₂ , C(=O)aryl, C(=O)Oalkyl, S(O) ₂alkyl , or alkylene-heterocyclile; R 7A is OH, halo, alkyl, haloalkyl, O-alkyl, OC(=O)alkyl, Si(alkyl) 3 , aryl, NH(C=O)alkyl, NH 2 , NH(alkyl), N(alkyl) 2 , or heterocyclile; Only R 9A is It is not; iii. R1 is -( CH2 ) n -R9B , where n is 1, 2, 3, 4, 5, or 6, and; R 9B is -O-alkylene-OH, -C(=O)-alkylene-NR 5 R 6 , R 7B having 1 to 4 aryls, Si(alkyl) 3 or -(OCH 2 CH 2 ) m is an alkylene-aryl substituted with -O-alkyl, m is 2 or 3, provided that R 9B is Si(alkyl) 3 or In this case, n is not 1; R 5 and R 6 are independently H, alkyl, C(=O)alkyl, C(=O)aryl, C(=O)Oalkyl, S(O) 2alkyl , alkylene-heterocyclile; R 7B is -OP(=O)OH 2 ,C 1-6 alkyl; iv. R1 is -N( R5A )( R6A ), where R 5A and R 6A are independently C 1-6 alkyls optionally substituted with H, -COOH, -OC(=O)alkyl or -O-alkylene-OH, and However, if one of R 5A and R 6A is H, the other cannot be H, CH 2 CH(CH 3 ) 2 , or (CH 2 ) 5 CH 3, and If one of R 5A and R 6A is CH 3 , the other is H, CH 3 or CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , or A compound that cannot be.
  2. In paragraph 1, The above compound is a compound of chemical formula (II). (II), or a pharmaceutically acceptable salt or deuterated form thereof, Among the above formulas R8 is alkynylene- NR5 R6 or - ( CH2CH2O ) m -alkyl; m is 1, 2, 3, 5, or 6; R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; R 5 and R 6 are compounds in which they are independently H, alkyl, C(=O)H, C(=O)alkyl, alkylene-heteroaryl, alkylene-aryl, alkylene-carbocyclil, alkylene-heterocyclil, S(=O)alkyl, or S(=O) 2alkyl .
  3. In paragraph 1 or 2, R8 is a C1-6 alkynyl substituted with N( C1-6 alkyl) 2 , or -( CH2CH2O ) m - CH3 , where m is 1, 2, or 3 .
  4. In any one of paragraphs 1 through 3, R 8 is Compounds that are -( CH₂CH₂O ) -CH₃ , -( CH₂CH₂O ) ₂ - CH₃ , or -( CH₂CH₂O ) ₃ - CH₃ .
  5. In paragraph 1, The above compound is a compound of chemical formula (III). (III), or a pharmaceutically acceptable salt or deuterated form thereof, Among the above formulas R9A is -C( RA ) 2NR5R6 , -C ( RA ) 2 -O-alkyl, -C( RA ) 2 -O-cycloalkyl, cycloalkyl substituted with O-alkyl, heterocyclyl substituted with C(=O)O-alkyl, alkenylene-aryl substituted with 1 to 4 R7A , alkenylene-heteroaryl substituted with 0 to 4 R7A , 5- membered heteroaryl substituted with 1 to 4 groups selected from aryl or alkyl, OH, halogen, haloalkyl, O-alkyl, or O-haloalkyl substituted with NR5R6 ; Each R A is independently H, halo, unsubstituted alkyl, or alkylene-OH, or Two R A groups form a cycloalkylene or heterocyclylene together with the carbons to which they are connected, and However, at least one R A is not H; R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; R5 and R6 independently are H, alkyl, or C(=O)alkyl, where the alkyl is optionally substituted with NH₂ , NH(alkyl), or N(alkyl) ₂ ; R 7A is OH, halo, alkyl, haloalkyl, O-alkyl, OC(=O)alkyl, Si(alkyl) 3 , aryl, NH(C=O)alkyl, NH 2 , NH(alkyl), N(alkyl) 2 , or heterocyclile; Only R 9A is A compound that is not a compound.
  6. In paragraph 5, R9A is selected from -C( RA ) 2NR5R6 , -C( RA ) 2- OC1-6 alkyl , -C( RA ) 2- OC3-6 cycloalkyl, cyclopropyl substituted with OC1-6 alkyl, heterocyclyl substituted with C (=O)OC1-6 alkyl , C1-6 alkenylene-aryl substituted with 1 to 4 R7A , C1-6 alkenylene-heteroaryl, arylene- NR5R6 , or pentagonal heteroaryl comprising 2 N atoms where the heteroaryl is substituted with C1-3 alkyl; Each RA is independently H or an unsubstituted alkyl, provided that at least one RA is not H, R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; R5 and R6 independently are H, alkyl, or C(=O)alkyl, where the alkyl is optionally substituted with NH₂ , NH(alkyl), or N(alkyl) ₂ ; R 7A is a compound that is OH, halo, alkyl, haloalkyl, O-alkyl, OC(=O)alkyl, Si(alkyl) 3 , aryl, -NH(C=O)alkyl, NH 2 , NH(alkyl), N(alkyl) 2 , or heterocyclil.
  7. In any one of Paragraph 1 or Paragraphs 5 through 6, R 9A a or Phosphorus compound.
  8. In paragraph 1, The above compound is a compound of chemical formula (IV). (IV), or a pharmaceutically acceptable salt or deuterated form thereof, Among the above formulas n is 1, 2, 3, 4, 5, or 6, and; R 9B is -O-alkylene-OH, -C(=O)-alkylene-NR 5 R 6 , R 7B with 1 to 4 aryls, Si(alkyl) 3 or -(OCH 2 CH 2 ) m -Oalkyl substituted alkylene-aryl; m is 2 or 3 and; R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; R 5 and R 6 are independently H, alkyl, C(=O)alkyl, C(=O)aryl, C(=O)Oalkyl, S(O) 2alkyl or alkylene-heterocyclile; R 7B is -OP(=O)OH 2 ,C 1-6 alkyl, and Only R 9B is Si(alkyl) 3 or In this case, n is a compound that is not 1.
  9. In paragraph 1 or paragraph 8, n is 1, 2, or 3, and; R 9B is -OC 1-6 alkylene-OH or -C(=O)-C 1-6 alkylene-NR 5 R 6 , R 7B with 1 to 4 aryls, Si(C 1-6 alkyl) 3 , -(OCH 2 CH 2 ) m -Oalkyl substituted C 1-6 alkylene-aryl; m is 2 or 3 and; R2 and R3 are independently alkyl; R 4 is H or C(=O)OC 1-6 alkyl; R 5 and R 6 are compounds in which they are independently H or alkyl.
  10. In any one of Paragraph 1 or Paragraphs 8 through 9, R 9B is or Phosphorus compound.
  11. In any one of Paragraph 1 or Paragraphs 8 through 10, n is 1, 2 or 3, and R 9B is or Phosphorus compound.
  12. In paragraph 1, The above compound is a compound of the chemical formula (V). or a pharmaceutically acceptable salt or deuterated form thereof, Among the above formulas R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; R 5A and R 6A are independently C 1-6 alkyls optionally substituted with H, -COOH, -OC(=O)alkyl or -O-alkylene-OH, and However, R 5A and R 6A are not both H, and if one of R 5A and R 6A is H, the other is H, -(CH 2 ) 5 CH 3 or CH 2 CH(CH 3 ) 2 cannot be, and Additionally, if one of R 5A and R 6A is CH 3 , the other is H, CH 3 , or CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , or A compound that cannot be.
  13. In paragraph 1 or paragraph 12, R 5A and R 6A independently contain H, CH 3 , or Phosphorus compound.
  14. Compound of chemical formula (VI) (V), or as a pharmaceutically acceptable salt or deuterated form thereof, Among the above formulas R is NR 5 R 6 and; R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; R 5 and R 6 are compounds that are independently H, alkyl, haloalkyl, or C(=O)haloalkyl.
  15. In Paragraph 14, A compound in which R₅ is H and R₆ is C(=O) CF₃ .
  16. Compound of chemical formula (VII) or as a pharmaceutically acceptable salt or deuterated form thereof, Among the above formulas R2 and R3 are independently alkyl; R c is OH or OC(=O)alkyl and; R 10 is NR 5A R 6A , O-alkylene-OC(=O)alkyl, O-alkylene-Si(alkyl) 2 , heterocyclic, or aryl; R 5A and R 6A are independently alkyl or alkylene-OC(=O)alkyl compounds.
  17. In Paragraph 16, R c is OH or OC(=O)C 1-6 alkyl; R 10 is NR 5A R 6A , OC 1-6 alkylene-OC(=O)C 1-6 alkyl, -OC 1-6 alkylene-Si(C 1-6 alkyl) 2 , 3 to 8-membered heterocycle or aryl; R 5A and R 6A are independently compounds that are C 1-6 alkyl or C 1-6 alkylene-OC(=O) C 1-6 alkyl.
  18. In paragraph 16 or 17, R c is OH or OC(=O)CH 3 , and R 10 is or Phosphorus compound.
  19. In any one of paragraphs 1 through 18, R2 and R3 are independently C1-6 alkyl compounds.
  20. In any one of paragraphs 1 through 19, R2 and R3 are compounds that are -CH3 .

Description

3-(2-(dimethylamino)ethyl)-1H-indole-4-yl derivative Cross-reference regarding related applications This application claims priority to U.S. Provisional Application No. 63/578,791 filed August 25, 2023, the disclosures of which are by reference in their entirety for all purposes. background More than 50% of American adults will be diagnosed with a mental disorder at some point in their lives. Nearly one in five people suffers from a mental illness, and nearly one in 25 people suffers from a severe mental illness such as major depressive disorder, schizophrenia, or bipolar disorder. Psychedelics exhibit promising activity in the treatment of mental illness. New psychedelic compounds are required for the treatment of mental illness. Simple explanation In some embodiments, the present disclosure comprises a compound of the following formula (I): or providing a pharmaceutically acceptable salt or deuterated form thereof, Among the above formulas R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; R 1 is defined according to i, ii, iii, or iv : i.R1 is -OR8 , where R8 is an alkynyl substituted with NR5R6 or -( CH2CH2O ) m -alkyl, where m is 1, 2, 3, 5 or 6; R 5 and R 6 are independently H, alkyl, C(=O)alkyl, alkylene-aryl, or S(O) 2alkyl ; ii.R1 is -R9A , where R9A is -C( RA ) 2NR5R6 , -C ( RA ) 2 -O-alkyl, -C( RA ) 2 -O-cycloalkyl, cycloalkyl substituted with O-alkyl, heterocyclyl substituted with C(= O )O-alkyl, alkenylene-aryl substituted with 1 to 4 R7A , alkenylene-heteroaryl substituted with 0 to 4 R7A , or aryl substituted with NR5R6 ; Each R A is independently H, halo, unsubstituted alkyl, or alkylene-OH, or Two R A groups form a cycloalkylene or heterocyclylene together with the carbons to which they are connected, and However, at least one R A is not H; R5 and R6 are independently H, alkyl, or , or C(=O)alkyl, where the alkyl is optionally substituted with NH₂ , NH(alkyl), N(alkyl) ₂ , C(=O)aryl, C(=O)Oalkyl, S(O) ₂alkyl , or alkylene-heterocyclile; R 7A is OH, halo, alkyl, haloalkyl, O-alkyl, OC(=O)alkyl, Si(alkyl) 3 , aryl, NH(C=O)alkyl, NH 2 , NH(alkyl), N(alkyl) 2 , or heterocyclile; Only R 9A is It is not, iii.R1 is -( CH2 ) n -R9B , where n is 1, 2, 3, 4, 5, or 6, and; R 9B is -O-alkylene-OH, -C(=O)-alkylene-NR 5 R 6 , R 7B having 1 to 4 aryls, Si(alkyl) 3 or -(OCH 2 CH 2 ) m is an alkylene-aryl substituted with -O-alkyl, where m is 2 or 3, 5 o 6, provided that R 9B is Si(alkyl) 3 or In this case, n is not 1; R 5 and R 6 are independently H, alkyl, C(=O)alkyl, C(=O)aryl, C(=O)Oalkyl, S(O) 2alkyl , alkylene-heterocyclile; R 7B is -OP(=O)OH 2 ,C 1-6 alkyl and; iv.R1 is -N( R5A )( R6A ), where R 5A and R 6A are independently C 1-6 alkyls optionally substituted with H, -COOH, -OC(=O)alkyl or -O-alkylene-OH, and However, if one of R 5A and R 6A is H, the other cannot be H, CH 2 CH(CH 3 ) 2 or (CH 2 ) 5 CH 3 , and Additionally, if one of R 5A and R 6A is CH 3 , the other is H, CH 3 , or CH 2 CH 3 , CH 2 CH(CH 3 ) 2 , or Cannot work. In some embodiments, the present disclosure comprises a compound of the following formula (I), or providing a pharmaceutically acceptable salt or deuterated form thereof, Among the above formulas R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; R 1 is defined according to i, ii, or iii : i.R1 is -OR8 , where R8 is -( CH2CH2O ) m -alkyl, m is 2, 3, 5 or 6; ii.R1 is -R9A , where R9A is -C( RA ) 2 -O-alkyl, -C( RA ) 2 -O-cycloalkyl, cycloalkyl substituted with OC1-6 alkyl, heterocyclyl substituted with C(=O)O alkyl, pentagonal heteroaryl containing two N atoms in which the heteroaryl is substituted with C1-3 alkyl, or arylene- NR5R6 ; R5 and R6 independently are H, alkyl, or C(=O)alkyl, where the alkyl is optionally substituted with NH₂ , NH(alkyl) or N(alkyl) ₂ , and Each R A is independently H, halo, unsubstituted alkyl, or alkylene-OH, or Two R A groups form a cycloalkylene or heterocyclylene together with the carbons to which they are connected, and However, at least one R A is not H; iii.R1 is -( CH2 ) n -R9B , where n is 1, 2, 3, 4, 5, or 6, and; R 9B is a branched alkylene-aryl substituted with 1 to 4 aryls of R 7B , Si(alkyl) 3 , or -(OCH 2 CH 2 ) m -O alkyl; R 7B is -OP(=O)OH 2 ,C 1-6 alkyl, and Only R 9B is Si(alkyl) 3 or In this case, n is not 1. definition The following terms as used herein have the following meanings unless otherwise indicated: "Cyano" refers to the -CN radical. "Hydroxy" or "hydroxyl" refers to the -OH radical. "Oxo" refers to the =O substituent. "Alkyl" or "alkyl group" refers to a fully saturated, linear, or branched hydrocarbon chain radical having 1 to 12 carbon atoms and attached to the rest of the molecule by single bonds. Alkyls comprising any number of carbon atoms from 1 to 12 are included. Alkyls comprising up to 12 carbon atoms are C1 - C12 alkyls, alkyls comprising up to 10 carbon atoms are C1 - C10 alkyls, alkyls comprising up to 6 carbon atoms are C1 - C6 alkyls, and alkyls comprising up to 5 carbon atoms are C1