Granted Patent B2

US 12,295,959 · App. 18/742,438 · Granted May 13, 2025

Inventors: Noel Aaron Powell (Westford, MA); Milan Chytil (Acton, MA); Florence F. Wagner (Ashland, MA)

Assignee: DELIX THERAPEUTICS, INC.

A61K31/55A61K9/0019A61K9/0053A61K9/08A61K9/2013A61K9/2054A61K9/4825A61K9/4866A61P25/24A61P25/28C07D487/04

Abstract

Claims (72)

1. A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

R 1 is OR a , wherein R a is an optionally substituted arylalkyl;

R 2 is hydrogen;

R 3 is hydrogen;

R 4 is hydrogen;

R 5 is an unsubstituted or substituted alkyl, or hydrogen; and

R 6 is an unsubstituted or substituted alkyl, or hydrogen.

2. The compound of claim 1 , wherein R 5 is hydrogen.

3. The compound of claim 1 , wherein R 5 is methyl.

4. The compound of claim 1 , wherein R 6 is hydrogen.

5. The compound of claim 1 , wherein R 6 is methyl.

6. The compound of claim 1 , wherein R 1 is an unsubstituted or substituted benzyloxy.

7. The compound of claim 1 , wherein R 1 is selected from the group consisting of unsubstituted benzyloxy and benzyloxy substituted with at least one halogen.

8. The compound of claim 1 , wherein R 1 is selected from the group consisting of benzyloxy and 4-fluorobenzyloxy.

9. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt or solvate thereof.

10. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

11. A method for treating a neurological disease or disorder in a mammal, the method comprising administering to the mammal the compound of claim 1 , or any pharmaceutically acceptable salt or solvate thereof.

12. The method of claim 11 , wherein the neurological disease or disorder is a neurodegenerative, a neuropsychiatric, or a substance use disease or disorder.

13. The method of claim 11 , wherein the neurological disease or disorder is selected from the group consisting of an anxiety disorder, a mood disorder, a psychotic disorder, a personality disorder, an eating disorder, a sleep disorder, a sexuality disorder, an impulse control disorder, a substance use disorder, a dissociative disorder, a cognitive disorder, a developmental disorder, and a factitious disorder.

14. The method of claim 11 , wherein the mammal is a human.

15. A compound of Formula (II), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

R 1 is hydrogen;

R 2 is hydrogen;

R 3 is OR a , wherein R a is an optionally substituted arylalkyl;

R 4 is hydrogen;

R 5 is an unsubstituted or substituted alkyl, or hydrogen; and

R 6 is an unsubstituted or substituted alkyl, or hydrogen.

16. The compound of claim 15 , wherein R 5 is hydrogen.

17. The compound of claim 15 , wherein R 5 is methyl.

18. The compound of claim 15 , wherein R 6 is hydrogen.

19. The compound of claim 15 , wherein R 6 is methyl.

20. The compound of claim 15 , wherein R 3 is an unsubstituted or substituted benzyloxy.

21. The compound of claim 15 , wherein R 3 is selected from the group consisting of unsubstituted benzyloxy and benzyloxy substituted with at least one halogen.

22. The compound of claim 15 , wherein R 3 is selected from the group consisting of benzyloxy and 4-fluorobenzyloxy.

23. The compound of claim 15 , wherein the compound is

or a pharmaceutically acceptable salt or solvate thereof.

24. A pharmaceutical composition comprising the compound of claim 15 , or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

25. A method for treating a neurological disease or disorder in a mammal, the method comprising administering to the mammal the compound of claim 15 , or any pharmaceutically acceptable salt or solvate thereof.

26. The method of claim 25 , wherein the neurological disease or disorder is a neurodegenerative, a neuropsychiatric, or a substance use disease or disorder.

27. The method of claim 25 , wherein the neurological disease or disorder is selected from the group consisting of an anxiety disorder, a mood disorder, a psychotic disorder, a personality disorder, an eating disorder, a sleep disorder, a sexuality disorder, an impulse control disorder, a substance use disorder, a dissociative disorder, a cognitive disorder, a developmental disorder, and a factitious disorder.

28. The method of claim 25 , wherein the mammal is a human.

29. A process for the preparation of a compound according to Group 1, Group 2, Group 3, Group 4, or Group 5:

Group 1: a process for the preparation of Compound A, Compound A′, or a pharmaceutically acceptable salt thereof:

comprising reacting Compound 1-4:

with Compound I-5:

in the presence of an acid to form Compound A, Compound A′, or a pharmaceutically acceptable salt thereof;

wherein Ar is substituted or unsubstituted aralkyl; or

Group 2: a process for the preparation of Compound B, Compound B′, or a pharmaceutically acceptable salt thereof:

comprising reacting Compound A or Compound A′ with formaldehyde to form Compound B, Compound B′ or a pharmaceutically acceptable salt thereof;

wherein Ar is substituted or unsubstituted aralkyl; or

Group 3: a process for the preparation of Compound C, or a pharmaceutically acceptable salt thereof:

comprising the steps of

i) reacting Compound A with Boc 2 O to form Compound I-6:

ii) reacting Compound I-6 with an alkylating agent to form Compound I-7:

and

iii) deprotecting Compound I-7 to form Compound C,

wherein Ar is substituted or unsubstituted aralkyl; or

Group 4: a process for the preparation of Compound D, or a pharmaceutically acceptable salt thereof:

comprising reacting Compound C with formaldehyde to form Compound D, or a pharmaceutically acceptable salt thereof,

wherein Ar is substituted or unsubstituted aralkyl; or

Group 5: a process for the preparation of a Compound 2, or a pharmaceutically acceptable salt thereof:

comprising the steps of:

i) reacting Compound 1-4g:

with Compound I-5b:

in the presence of an acid to form Compound 29:

and

ii) reacting Compound 29 in the presence of a reducing agent to form Compound 2, or a pharmaceutically acceptable salt thereof.

30. A compound selected from:

or a salt thereof.

Assignments (2)

Continuity (4)

References Cited (362)