Granted Patent B2

US 12,319,682 · App. 18/637,083 · Granted Jun 3, 2025

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

Abstract

Claims (67)

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

wherein:

G is CH or N;

R1 is H, C1-C4-alkyl, HO-C 1 -C 4 -alkyl or C 1 -C 4 -alkyl-O—C 1 -C 4 -alkyl; and

R 2 is selected from group consisting of:

(a) phenyl group unsubstituted or substituted with at least one substituent, or

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

wherein the substituent is selected from a group consisting of F, Cl, Br, C 1 -C 4 -alkyl-, and C 1 -C 4 -alkyl -O—;

or a pharmaceutically acceptable salt thereof, and scopolamine.

2. The pharmaceutical composition of claim 1 , wherein R 1 is H, methyl, or 2-hydroxyethyl.

3. The pharmaceutical composition of claim 1 , wherein the 5-or 6-membered heteroaryl is furyl, thienyl, thiazolyl, or pyridyl.

4. The pharmaceutical composition of claim 1 , wherein the substituent is selected from a group consisting of F, Cl, methyl and methoxy.

5. The pharmaceutical composition of claim 1 , wherein the compound is selected from a group consisting of the following:

1-benzyl-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H -benzimidazole;

1-benzyl-4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)-1H -benzimidazole;

2-{4-[1-benzyl-2-(trifluoromethyl)-1H-benzimidazol-4-yl]piperazin-1-yl}ethanol;

1-(furan-2-ylmethyl)-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H -benzimidazole;

1-[(5-methylfuran-2-yl) methyl]-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-benzimidazole;

1-(3-chlorobenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H -benzimidazole;

1-(3-fluorobenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H -benzimidazole;

1-(3, 4-dichlorobenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl) -1H-benzo [d]imidazole;

1-(3-chloro-4-fluorobenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-benzo [d]imidazole;

1-(3, 4-difluorobenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl) -1H-benzo [d]imidazole;

1-(3, 5-dichlorobenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl) -1H-benzo [d]imidazole;

1-benzyl-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-indole;

1-(3, 4-dichlorobenzyl)-4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)-1H-indole;

1-(4-chloro-3-fluorobenzyl)-4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)-1H-indole;

4-(piperazin-1-yl)-1-(1,3-thiazol-2-ylmethyl)-2-(trifluoromethyl)-1H-indole;

1-(4-chloro-3-fluorobenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-indole;

1-(furan-2-ylmethyl)-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H -indole;

1-(3-methoxybenzyl)-4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)-1H-indole;

1-(3-fluorobenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H -indole;

1-(3-chloroobenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H -indole;

1-(furan-2-ylmethyl)-4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)-1H-indole;

1-(3, 4-difluorobenzyl)-4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)-1H-indole;

1-(3-methoxybenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H -indole;

1-(3-fluorobenzyl)-4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)-1H-indole;

1-(3, 4-difluorobenzyl)-4-(piperazin-1-yl)-2-(trifluoromethyl) -1H-indole;

1-benzyl-4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)-1H -indole;

1-(3-chlorobenzyl)-4-(4-methylpiperazin-1-yl)-2-(trifluoromethyl)-1H-indole;

1-[(5-methylfuran-2-yl) methyl]-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-indole;

1-[(5-methylthiophen-2-yl) methyl]-4-(piperazin-1-yl)-2-(trifluoromethyl)-1H-indole; 4-(piperazin-1-yl)-1-(thiophen-2-ylmethyl)-2-(trifluoromethyl) -1H-indole;

4-(piperazin-1-yl)-1-(thiophen-3-ylmethyl)-2-(trifluoromethyl) -1H-indole;

4-(4-methylpiperazin-1-yl)-1-(thiophen-3-ylmethyl)-2-(trifluoromethyl)-1H-indole;

4-(4-methylpiperazin-1-yl)-1-(thiophen-2-ylmethyl)-2-(trifluoromethyl)-1H-indole; and

4-(4-methylpiperazin-1-yl)-1-[(5-methyl-1, 3-thiazol-2-yl) methyl]-2-(trifluoromethyl)-1H-indole, or pharmaceutically acceptable salt thereof.

6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises

or pharmaceutically acceptable salt thereof; and scopolamine.

7. The pharmaceutical composition of claim 1 ,

wherein the pharmaceutical composition comprises the hydrochloride salt of

and scopolamine.

8. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises the hydrochloride salt of

and scopolamine.

9. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition comprises 0.1-1000 mg of

10. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition comprises 0.1-10 mg of

11. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition comprises 10-100 mg of

12. The pharmaceutical composition of claim 7 , wherein the pharmaceutical composition comprises 0.1-1000 mg of the hydrochloride salt of

13. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition comprises 0.1-10 mg of the hydrochloride salt of

14. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition comprises 10-100 mg of the hydrochloride salt of

15. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises

or

or pharmaceutically acceptable salt thereof; and scopolamine.

16. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition comprises 0.1-1000 mg of

17. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises 0.1-10 mg of

18. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises 10-100 mg of

19. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition comprises the hydrochloride salt of

20. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition comprises 0.1-1000 mg of the hydrochloride salt of

Assignments (1)

Priority Claims (1)

Continuity (3)

References Cited (16)