IP Library › Granted Patent US 12,552,790
Granted Patent B2
US 12,552,790 · App. 19/002,368 · Granted Feb 17, 2026

Positive modulators of the muscarinic acetylcholine receptor M4

Inventors: Craig W. Lindsley (Brentwood, TN); Darren W. Engers (Brentwood, TN); Kayla J. Temple (Spring Hill, TN); Alison R. Gregro (Mount Juliet, TN); Alexa E. Richardson (Nashville, TN); Madeline F. Long (Nashville, TN)
Assignee: Vanderbilt University
C07D471/04A61K31/4545C07B59/002
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Quick Facts
Patent No.
US 12,552,790
App. No.
19/002,368
Granted
Feb 17, 2026
Kind
B2
Abstract

Deuterium-labeled 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxy)piperidines substituted with pyrrolo[3,4-b]pyridin-5-one, furo[3,4-b]pyridin-5(7H)-one, or [1,2,4]triazolo[4,3-a]pyrimidin-3(2H)-one are positive allosteric modulators of the muscarinic acetylcholine receptor M 4 (mAChR M 4 ) and may have use in treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction.

Claims (10)

1 . A method of preparing a product having a structure of Compound 3:

2-(4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl-2,2,3,3-d 4 )oxy)piperidin-1-yl)-3-methyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one, wherein the method comprises:

(a) contacting tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate with 2,3-dihydrobenzo[b][1,4]dioxin-2,2,3,3-d 4 -6-ol, a quaternary ammonium salt, and a base, to form tert-butyl 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl-2,2,3,3-d 4 )oxy)piperidine-1-carboxylate;

(b) contacting the tert-butyl 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl-2,2,3,3-d 4 )oxy)piperidine-1-carboxylate with acid to form an acid addition salt of 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl-2,2,3,3-d 4 )oxy)piperidine; and

(c) contacting the acid addition salt of 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl-2,2,3,3-d 4 )oxy)piperidine with 2-chloro-3-methyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one and a base to form Compound 3.

2 . The method of claim 1 , wherein step (a) further comprises heating the tert-butyl 4-methylsulfonyloxypiperidine-1-carboxylate with 2,3-dihydrobenzo[b][1,4]dioxin-2,2,3,3-d 4 -6-ol, a quaternary ammonium salt, and base.

3 . The method of claim 2 , wherein the quaternary ammonium salt of step (a) is a tetrabutylammonium salt.

4 . The method of claim 1 , wherein the acid of step (b) is trifluoroacetic acid.

5 . The method of claim 1 , wherein step (c) further comprises heating the acid addition salt of 4-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl-2,2,3,3-d 4 )oxy)piperidine with 2-chloro-3-methyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-5-one and base.

6 . The method of claim 5 , wherein the base of step (c) is an alkylamine base.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 31, 2024
From: LINDSLEY, CRAIG W.; ENGERS, DARREN W.; TEMPLE, KAYLA J.; GREGRO, ALISON R.; RICHARDSON, ALEXA E.; LONG, MADELINE F.
To: VANDERBILT UNIVERSITY
Reel/Frame 069832/0049 →
Continuity (4)
Continuation 18750829 · Jun 21, 2024
Provisional Application 63610220 · Dec 14, 2023
Provisional Application 63509589 · Jun 22, 2023
Related Publication 20250136600A1 · May 1, 2025
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