IP Library Granted Patent US 11,981,668
Granted Patent B2
US 11,981,668 · App. 17/326,159 · Granted May 14, 2024

Indole and benzimidazole derivatives as dual 5-HT2A and 5-HT6 receptor antagonists

Inventors: Marcin Kolaczkowski (Wieliczka, PL); Adam Bucki (Przebieczany, PL); Joanna Sniecikowska (Wieliczka, PL); Monika Marcinkowska (Cracow, PL)
Assignee: ADAMED PHARMA S.A.
C07D417/14A61P25/28C07D403/10C07D405/14C07D409/14
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Quick Facts
Patent No.
US 11,981,668
App. No.
17/326,159
Granted
May 14, 2024
Kind
B2
Abstract

The invention relates to new 4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-indoles and 4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-benzimidazoles represented by formula (I), wherein all symbols and variables are as defined in the description. The compounds can find use in a method of prevention and/or treatment of diseases selected from the group consisting of Alzheimer's disease, Parkinson's disease, Lewy body dementia, dementia-related psychosis, schizophrenia, delusional syndromes and other psychotic conditions related and not related to taking psychoactive substances, depression, anxiety disorders of various aetiology, sleep disorders of various aetiology.

Claims (35)

1. A method of antagonizing both 5-HT2A and 5-HT6 receptors in a subject comprising administering to a subject an effective amount of a compound having the structure:

wherein:

G is CH or N;

R 1 is H, C 1 -C 4 -alkyl, HO—C 1 -C 4 -alkyl or C 1 -C 4 -alkyl-O—C 1 -C 4 -alkyl;

R 2 is selected from group consisting of:

phenyl group unsubstituted or substituted with at least one substituent, or

5- or 6-membered heteroaryl group unsubstituted or substituted with at least one substituent,

wherein the substituent is selected from F, Cl, Br, C 1 -C 4 -alkyl-, C 1 -C 4 -alkyl-O—

or a pharmaceutically acceptable salt thereof, so as to thereby antagonize both 5-HT2A and 5-HT6 receptors in the subject.

2. The method of claim 1 , wherein the method is for treating a subject afflicted with schizoaffective disorders, schizophreniform disorders, affective disorder, bipolar disorder, mania, stress reactions, consciousness disorders, coma, alcoholic delirium and of various aetiology, aggression, psychomotor agitation, and other conduct disorders, withdrawal syndromes of various aetiology, addiction, pain syndromes of various aetiology, intoxication with psychoactive substances, cerebral circulatory disorders of various aetiology, psychosomatic disorders of various aetiology, conversion disorders, dissociative disorders, urinary disorders, autism and other developmental disorders.

3. The method of claim 1 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

4. The method of claim 1 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

5. The method of claim 2 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

6. The method of claim 2 , wherein the compound has the structure:

or a pharmaceutical acceptable salt thereof.

7. The method of claim 2 , wherein the compound has the structure:

or a pharmaceutical acceptable salt thereof.

8. The method of claim 2 , wherein the compound has the structure:

or a pharmaceutical acceptable salt thereof.

9. The method of claim 3 , wherein the method comprises treating a subject afflicted with Alzheimer's disease, Parkinson's disease, Lewy body dementia, dementia-related psychosis, schizophrenia, delusional syndromes and other psychotic conditions related and not related to taking psychoactive substances, depression, anxiety disorders of various aetiology, or sleep disorders of various aetiology.

10. The method of claim 3 , wherein the effective amount of 0.1-1000 mg of the compound is administered to the subject.

11. The method of claim 5 , wherein the effective amount of 0.1-10 mg of the compound is administered to the subject.

12. The method of claim 5 , wherein the effective amount of 10-100 mg of the compound is administered to the subject.

13. The method of claim 6 , wherein the effective amount of 0.1-10 mg of the compound is administered to the subject.

14. The method of claim 6 , wherein the effective amount of 10-100 mg of the compound is administered to the subject.

15. The method of claim 7 , wherein the effective amount of 0.1-10 mg of the compound is administered to the subject.

16. The method of claim 7 , wherein the effective amount of 10-100 rug of the compound is administered to the subject.

17. The method of claim 8 , wherein the effective amount of 0.1-10 mg of the compound is administered to the subject.

18. The method of claim 8 , wherein the effective amount of 10-100 mg of the compound is administered to the subject.

19. A pharmaceutical composition comprising a compound having the structure:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

20. The method of claim 1 , wherein the compound is administered to the subject orally.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 24, 2021
From: KOLACZKOWSKI, MARCIN; BUCKI, ADAM; SNIECIKOWSKA, JOANNA; MARCINKOWSKA, MONIKA
To: ADAMED PHARMA S.A.
Reel/Frame 056331/0540 →
Priority Claims (1)
EP 18461519 · Feb 21, 2018 · regional
Continuity (2)
Continuation 16970871
Related Publication 20210276995A1 · Sep 9, 2021
Cited By (1)
US 12,319,682