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KR-20260065837-A - 3-(2-(dimethylamino)ethyl)-1H-indole-4-yl oligomer derivative

KR20260065837AKR 20260065837 AKR20260065837 AKR 20260065837AKR-20260065837-A

Abstract

In this specification, compounds of the following formulas (I), (II), and (III), compounds selected from any of the compounds in Tables 1, 2, 3, and 4, or pharmaceutically acceptable salts or deuterated forms thereof are provided, wherein R1 , R2 , R3 , R4 , RD , RG , p, and q are defined herein. In addition, in this specification, a pharmaceutical composition comprising the compound of formula (I), or a compound selected from any of the compounds in Tables 1, 2, 3, and 4, or pharmaceutically acceptable salts or deuterated forms thereof, and a method of using the compounds of formulas (I), (II), and (III), or pharmaceutically acceptable salts or deuterated forms thereof, for example, in treating 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
20260511
Application Date
20240823
Priority Date
20230825

Claims (20)

  1. Compound of the following chemical formula (I) or as a pharmaceutically acceptable salt thereof or a deuterated form thereof, R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; p is 2 or 3 and; R D is alkylene, alkenylene, alkylene-O-alkylene, -( CH₂ ) n - ( OCH₂CH₂ ) m -, cycloalkylene, or arylene, or A divalent or trivalent group selected from, each of which is optionally substituted with 1 to 4 groups selected from halogen, OH, Oalkyl, alkyl, NH₂ , NH(alkyl), N(alkyl) ₂ , C(=O)OH, C(=O)Oalkyl, OC(=O)alkyl, or C(=O)alkyl; n is 1, 2, 3, 4, 5, 6, 7 or 8, and; m is 1, 2, 3, 4, 5, 6, 7 or 8 and; r is 1, 2, or 3, and; Provided, where R2 and R3 are each dedehydrogenated alkyl, RD is CH2 , ( CH2 ) 2 , ( CH2 ) 3 , ( CH2 ) 4 , ( CH2 ) 5 , ( CH2 ) 8 , , , , or It is not, However, if R2 and R3 are each CD3 , RD is a compound other than ( CH2 ) 3 .
  2. In paragraph 1, R D is C 1-12 alkylene, C 1-6 alkylene-OC 1-6 alkylene, -(CH 2 ) n -(OCH 2 CH 2 ) m -, C 3-8 cycloalkylene , arylene or A compound in which a divalent or trivalent group selected from, each of which is optionally substituted with 1 to 4 groups selected from C1-3 alkyl, OH, OCH3 , NH2 , COOH, or C(=O)alkyl.
  3. In paragraph 1, R D is alkylene-O-alkylene, -( CH₂ ) n -( OCH₂CH₂ ) m -, cycloalkylene, heterocyclylene, arylene, heteroarylene , or A compound in which a divalent or trivalent group selected from, each of which is optionally substituted with OH, OCH₃ , NH₂ , COOH, cycloalkyl, or C(=O)alkyl.
  4. In paragraph 1 or 3, R D is C 1-6 alkylene-O- C 1-6 alkylene, -(CH 2 ) n -(OCH 2 CH 2 ) m -, C 3-8 cycloalkylene, 3-8 heterocyclylene, arylene, heteroarylene or A compound in which a divalent or trivalent group selected from, each of which is optionally substituted with OH, OCH₃ , NH₂ , COOH, cycloalkyl, or C(=O)alkyl.
  5. In paragraph 1, The above compound has the following chemical formula (Ia) or a pharmaceutically acceptable salt or deuterated thereof, Here Each of R2 and R3 is independently alkyl; Each R 4 is independently H or C(=O)O alkyl; RES is alkylene, cycloalkylene, arylene, alkylene-O-alkylene, -( CH₂ ) n - ( OCH₂CH₂ ) m - or A divalent group selected from, each of which is optionally substituted with one or more groups selected from halogen, alkyl, Oalkyl, NH2 , NHC 1-6 alkyl, NC( 1-6 alkyl) 2 , COOH, cycloalkyl, and C(=O)Oalkyl; n is 1, 2, or 3, and; m is 1, 2, or 3 and; A compound where r is 1, 2, or 3.
  6. In paragraph 5, RES is C 1-12 alkylene, C 3-8 cycloalkylene, arylene, C 1-6 alkylene , OC 1-6 alkylene, -(CH 2 ) n - ( OCH 2 CH 2 ) m - or A compound in which a divalent group selected from, each of which is optionally substituted with one or more groups selected from halogen, C1-3 alkyl, O alkyl, NH2 , NHC1-6 alkyl, NC( 1-6 alkyl) 2 , COOH, C3-8 cycloalkyl, and C(=O)O alkyl.
  7. In paragraph 5 or 6, A compound in which the above alkylene group is linear or branched.
  8. In paragraph 6 or 7, The above alkylene group is a branched compound.
  9. In any one of paragraphs 1 through 8, R D or R E is , , , , , -(CH 2 ) 2 -(OCH 2 CH 2 ) 2 -, -(CH 2 ) 2 -(OCH 2 CH 2 ) 3 -, , , , , or Phosphorus compound.
  10. In paragraph 1, The above compound is a compound of the following chemical formula (Ib). or a pharmaceutically acceptable salt or deuterated form thereof, Here Each of R2 and R3 is independently alkyl; Each R 4 is independently H or C(=O)O alkyl; RF is a compound that is a trivalent cycloalkylene or alkylene group.
  11. In Paragraph 10, RF is a compound that is a trivalent C3-8 cycloalkylene.
  12. In Article 10 or Article 11, R F is Phosphorus compound.
  13. Compound of the following chemical formula (IIa) or as a pharmaceutically acceptable salt or deuterated form thereof, Here Each of R2 and R3 is independently alkyl; Each R 4 is independently H or C(=O)O alkyl; RH is --( CH₂ ) n - ( OCH₂CH₂ ) m- or alkylene; n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12, and m is 1, 2, or 3 and; If R2 and R3 are each CH3 , RH is a compound that is not --( CH2 ) 2- or --( CH2 ) 3- .
  14. In Paragraph 13, n is 1, 2, 3, 4, 5, 6, 7, 8, and, A compound where m is 1, 2, or 3.
  15. In paragraph 13 or 14, A compound in which RH is -( CH2 ) 5- , -( CH2 ) 8- , or -( CH2 ) 2- ( OCH2CH2 ) 2 .
  16. Compound of the following chemical formula (III) or as a pharmaceutically acceptable salt thereof or a deuterated form thereof, Here R2 and R3 are independently alkyl; R 4 is H or C(=O)O alkyl; R1 is alkylene-C(=O)OH (wherein the alkylene is optionally substituted with OH, C(=O)OH, -OC(=O)alkyl or NH2 ), alkenylene-C(=O)OH (wherein the alkenylene is optionally substituted with C(=O)OH), cycloalkylene-C(=O)OH (wherein the cycloalkylene is optionally substituted with C(=O)OH), arylene-C(=O)OH (wherein the arylene is optionally substituted with alkyl, Oalkyl or C(=O)OH), -( CH2CH2O ) m -( CH2CH2 ) n -C(= O )OH, alkylene -O-alkylene-C(=O)OH, arylene-O(C=O)-alkylene-C(=O)O-arylene-C(=O)OH, O-alkylene-OH (wherein the alkylene is Optionally substituted with OH), or - ( OCH₂CH₂ ) m -OH and; m is 1, 2, 3 and; n is 1, 2, 3, and, If R2 and R3 are each alkyl, R1 is ( CH2 ) 2C (=O)OH, ( CH2 ) 3C (=O)OH, -CH=CHC(=O)OH or A compound that is not this.
  17. In Paragraph 16, R1 is C1-10 alkylene-C(=O)OH (wherein the alkylene is optionally substituted with OH, C(=O ) OH, -OC(=O)alkyl or NH2 ), C1-6 alkenylene-C(=O)OH (wherein the alkenylene is optionally substituted with C ( =O)OH), C3-6 cycloalkylene-C(=O)OH (wherein the cycloalkylene is optionally substituted with C(=O)OH), arylene-C(=O)OH (wherein the arylene is optionally substituted with alkyl, Oalkyl or C(=O)OH), -( CH2CH2O ) m - ( CH2CH2 ) n -C(=O)OH, C1-6 alkylene-O- C1-6 alkylene-C(=O)OH, arylene-O(C=O) -C1-6 A compound of alkylene-C(=O)O-arylene-C(=O)OH, OC 1-10 alkylene-OH (wherein the alkylene is optionally substituted with OH), or -(OCH 2 CH 2 ) m -OH.
  18. In paragraph 16 or 17, R 1 is , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , or Phosphorus compound.
  19. In any one of paragraphs 16 through 18, R1 is a compound that is -( CH2CH2O ) m -( CH2CH2 ) n -C ( =O)OH.
  20. In any one of paragraphs 15 through 19, R 1 is , , Phosphorus compound.

Description

3-(2-(dimethylamino)ethyl)-1H-indole-4-yl oligomer derivative Cross-reference regarding related applications This application claims priority to U.S. Provisional Application No. 63/578,799 filed August 25, 2023, the disclosures of which are incorporated by reference in their entirety for all purposes. In the United States, 50% of adults will be diagnosed with a mental disorder at some point in their lives. Nearly one in five people suffers from psychosis, and nearly one in 25 people suffers from severe psychosis, such as major depressive disorder, schizophrenia, or bipolar affective disorder. Figure 1 shows pharmacokinetic data of compound (122) via subcutaneous administration. definition The following terms as used in this specification have the following meanings unless otherwise indicated. 'Cyan' 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 containing any number of carbon atoms from 1 to 12 are included. Alkyls containing up to 12 carbon atoms are C1 - C12 alkyls, alkyls containing up to 10 carbon atoms are C1 - C10 alkyls, alkyls containing up to 6 carbon atoms are C1 - C6 alkyls, and alkyls containing up to 5 carbon atoms are C1 - C5 alkyls. C1 - C5 alkyls include C5 alkyls, C4 alkyls, C3 alkyls, C2 alkyls, and C1 alkyls (i.e., methyl). C1 - C6 alkyls include all the moiety described above for C1 - C5 alkyls, but also include C6 alkyls. C1 - C10 alkyls include all the moiety described above for C1 - C5 alkyls and C1 - C6 alkyls, but also include C7 , C8 , C9 , and C10 alkyls. Similarly, C1 - C12 alkyls include all the aforementioned portions, but also include C11 and C12 alkyls. Non-limiting examples of C1 - C12 alkyls include methyl, ethyl, n-propyl, i-propyl, sec-propyl, n-butyl, i-butyl, sec-butyl, t-butyl, n-pentyl, t-amyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, and n-dodecyl. Unless otherwise specifically stated in the specification, the alkyl group may be optionally substituted. “Alkylene” or “alkylene chain” refers to a fully saturated, linear or branched polyvalent (e.g., divalent, trivalent, or tetravalent) hydrocarbon chain radical having 1 to 12 carbon atoms. Non-limiting examples of C1 – C12 alkylenes include methylene, ethylene, propylene, n-butylene, etc. As a non-limiting example, the alkylene chain is attached to the remainder of the molecule and to the radical group via a single bond. The points where the alkylene chain is attached to the remainder of the molecule and to the radical group may be formed through one carbon or any two or more carbons within the chain. Unless otherwise specifically stated in this specification, the alkylene chain may be optionally substituted. "Alkenyl" or "alkenyl group" refers to a linear or branched hydrocarbon chain radical having 2 to 12 carbon atoms and one or more carbon-carbon double bonds. Each alkenyl group is attached to the rest of the molecule by a single bond. Alkenyl groups containing any number of carbon atoms from 2 to 12 are included. Alkenyl groups containing up to 12 carbon atoms are C2 - C12 alkenyls, alkenyls containing up to 10 carbon atoms are C2 - C10 alkenyls, alkenyl groups containing up to 6 carbon atoms are C2 - C6 alkenyls, and alkenyls containing up to 5 carbon atoms are C2 - C5 alkenyls. C2 - C5 alkenyls include C5 alkenyls, C4 alkenyls, C3 alkenyls, and C2 alkenyls. C2 - C6 alkenyls include all the moiety described above for C2 - C5 alkenyls and also include C6 alkenyls. C2 - C10 alkenyls include all the moiety described above for C2 - C5 alkenyls and C2 - C6 alkenyls and also include C7 , C8 , C9 , and C10 alkenyls. Similarly, C2 - C12 alkenyls include all the previously mentioned moietys and also include C11 and C12 alkenyls. Non-limiting examples of C2 - C12 alkenyls include ethenyl (vinyl), 1-propenyl, 2-propenyl (allyl), iso-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-heptenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 1-octenyl, 2-octenyl, 3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 1-nonenyl, 2-nonenil, 3-nonenil, 4-nonenil, 5-nonenil, 6-nonenil, 7-nonenil, 8-nonenil, 1-desenil, 2-desenil, 3-desenil, 4-desenil, 5-desenil, 6-desenil, 7-desenil, 8-desenil, 9-desenil, 1-undesenil, 2-undesenil, 3-undesenil, 4-undesenil, 5-undesenil, 6-undesenil, 7-undesenil, 8-undesenil, 9-undesenil, 10-undesenil, 1-dodesenil, 2-dodesenil, 3-dodesenil, 4-dodesenil, 5-dodesenil, 6-dodesenil, Includes 7-dodecenyl, 8-dodecenyl, 9-dodecenyl, 10-dodecenyl, and 11-dodecenyl. Unless otherwise specifically stated in this specification, the alkenyl group may be optionally substituted. “Alkenylene” or “alkenylene chain” re