IP Library › Granted Patent US 12,269,818
Granted Patent B2
US 12,269,818 · App. 18/444,450 · Granted Apr 8, 2025

Analogs of xanomeline

Inventors: Samuel Clark (Miami, FL); Matthew Duncton (Las Vegas, NV)
Assignee: Terran Biosciences Inc.
C07D417/04
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,269,818
App. No.
18/444,450
Granted
Apr 8, 2025
Kind
B2
Abstract

Disclosed herein are xanomeline analogs, as well as methods for making and using the analogs to, for example, treat neuropsychiatric disorders.

Claims (51)

1. A compound according to the following formula:

wherein:

R 1 and R 2 are independently selected from hydrogen and C 1-6 alkyl;

R 3 is —C(O)R 5 ;

R 5 is C 1-14 alkyl; and

X − is a pharmaceutically acceptable counterion.

2. The compound of claim 1 , wherein R 1 is H.

3. The compound of claim 1 , wherein R 2 is C 1-2 alkyl.

4. The compound of claim 1 , wherein:

(i) R 1 is H, and R 2 is C 1-2 alkyl; or

(ii) R 1 is H, and R 2 is H.

5. The compound of claim 1 , wherein R 5 is C 4-12 alkyl.

6. The compound of claim 1 , wherein R 5 is C 4 alkyl, C 7 alkyl, or C 12 alkyl.

7. The compound of claim 1 , wherein:

(i) R 1 is H, R 2 is H, and R 5 is C 7 alkyl or C 12 alkyl; or

(ii) R 1 is H, R 2 is C 1-2 alkyl, and R 5 is C 4 alkyl.

8. The compound of claim 1 , wherein the compound

9. A pharmaceutical composition comprising the compound of claim 8 and a pharmaceutically acceptable excipient.

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

11. A pharmaceutical composition comprising the compound of claim 3 and a pharmaceutically acceptable excipient.

12. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the compound of claim 10 to the subject.

13. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition of claim 11 to the subject.

14. The compound of claim 10 , wherein the compound is

15. The compound of claim 14 , wherein the compound is:

16. A pharmaceutical composition comprising the compound of claim 15 and a pharmaceutically acceptable excipient.

17. A method for treating a neuropsychiatric disease, in a subject in need thereof, comprising administering an effective amount of the compound of claim 15 to the subject.

18. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition of claim 16 to the subject.

19. The compound of claim 14 , wherein the compound is:

20. A pharmaceutical composition comprising the compound of claim 19 and a pharmaceutically acceptable excipient.

21. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the compound of claim 19 to the subject.

22. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition of claim 20 to the subject.

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

24. A pharmaceutical composition comprising the compound of claim 23 and a pharmaceutically acceptable excipient.

25. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the compound of claim 23 to the subject.

26. The compound of claim 1 , wherein R 5 is C 1 -C 5 alkyl.

27. The compound of claim 26 , wherein R 1 is H and R 2 is H.

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

29. The compound of claim 28 , wherein the compound is

30. A pharmaceutical composition comprising the compound of claim 28 and a pharmaceutically acceptable excipient.

31. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the compound of claim 28 to the subject.

32. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition of claim 30 to the subject.

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

34. The compound of claim 33 , wherein the compound is

35. A pharmaceutical composition comprising the compound of claim 33 and a pharmaceutically acceptable excipient.

36. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the compound of claim 33 to the subject.

37. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition of claim 35 to the subject.

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

39. The compound of claim 38 , wherein the compound is

40. A pharmaceutical composition comprising the compound of claim 38 and a pharmaceutically acceptable excipient.

41. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the compound of claim 38 to the subject.

42. A method for treating a neuropsychiatric disease in a subject in need thereof, comprising administering an effective amount of the pharmaceutical composition of claim 40 to the subject.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2024
From: CLARK, SAMUEL; DUNCTON, MATTHEW
To: TERRAN BIOSCIENCES INC.
Reel/Frame 068132/0986 →
Continuity (3)
Provisional Application 63523619 · Jun 27, 2023
Provisional Application 63461543 · Apr 24, 2023
Related Publication 20240368149A1 · Nov 7, 2024
References Cited (25)
US 5043345A · Sauerberg et al. · 1991 [cited by applicant]
US 5545638A · Greenwood · 1996 [cited by applicant]
US 5750541A · Bymaster et al. · 1998 [cited by applicant]
US 6043258A · Bymaster et al. · 2000 [cited by applicant]
US 6083957A · Olesen et al. · 2000 [cited by applicant]
US 9670200B2 · Almarsson et al. · 2017 [cited by applicant]
US 10265311B2 · Elenko et al. · 2019 [cited by applicant]
US 10933020B2 · Betancourt et al. · 2021 [cited by applicant]
US 20200323839A1 · Elenko et al. · 2020 [cited by applicant]
US 20210145810A1 · Monn et al. · 2021 [cited by applicant]
US 20220144817A1 · Bennett · 2022 [cited by examiner]
WO WO9429303A1 · 1994 [cited by applicant]
WO WO2020172516A1 · 2020 [cited by applicant]
WO WO2022052936A1 · 2022 [cited by applicant]
WO WO2022182733A1 · 2022 [cited by applicant]
WO WO2024226691A1 · 2024 [cited by applicant]
Albert, D.H., et al.; “Ex vivo inhibition of beta-thromboglobulin release following administration to man of ABT-299, a novel prodrug of a potent platelet activating factor antagonist,” Inflammation Research; 46(7):272-… [cited by applicant]
Kane, B.E., et al.; “Synthesis and evaluation of xanomeline analogs—probing the wash-resistant phenomenon at the M1 muscarinic acetylcholine receptor,” Bioorg Med Chem .; 16(3):1376-1392 (2008). [cited by applicant]
Maspero, M., et al.; “Tacrine-xanomeline and tacrine-iperoxo hybrid ligands: Synthesis and biological evaluation at acetylcholinesterase and M1 muscarinic acetylcholine receptors,” Bioorganic Chemistry, 96:103633, pp. 1… [cited by applicant]
Matera, C., et al.; “Novel Xanomeline-Containing Bitopic Ligands of Muscarinic Acetylcholine Receptors: Design, Synthesis and FRET Investigation,” Molecules, 28(5):2407, pp. 1-24, doi: 10.3390/molecules28052407 (2023). [cited by applicant]
Pubchem SID 272884427: 1,2,5,6-Tetrahydro-1-methyl-3-[4-hexyloxy-1,2,5-thiadiazole-3- yllpyridine 1-oxide. Pubchem Deposit Date: Dec. 15, 2015 [retrieved online Sep. 4, 2024] URL: https://pubchem.ncbi.nlm.nih.gov/substa… [cited by applicant]
Ring, B.J., et al.; “Flavin-containing monooxygenase-mediated N-oxidation of the M(1)-muscarinic agonist xanomeline,” Drug Metabolism and Disposition, 27(10): 1099-1103 (1999). [cited by applicant]
Sauerberg, P., et al.; “Novel functional M1 selective muscarinic agonists. Synthesis and structure-activity relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1-methylpyridines,” Journal of Medicinal Chemistry, … [cited by applicant]
Sunagawa, M., et al.; “New anti-MRSA and anti-VRE carbapenems; synthesis and structure-activity relationships of 1beta-methyl-2-(thiazol-2-ylthio)carbapenems,” The Journal of Antibiotics (Tokyo), 55(8):722-757; doi: 10.… [cited by applicant]
Volpato, D.; “Bitopic Ligands and their molecular fragments for the study of the M1 Muscarinic Receptor,” University of Wuerzburg, Thesis; 285 pages [retrieved online Sep. 4, 2024]URL: https://opus.bibliothek.uni-wuerzb… [cited by applicant]