Granted Patent B2

US 12,637,464 · App. 18/554,762 · Granted May 26, 2026

Inventors: David E. Olson (Oakland, CA); Jeremy R. Tuck (Oakland, CA); Lee E. Dunlap (Oakland, CA)

Assignee: The Regents of the University of California

C07D471/14A61P25/00

Abstract

Claims (30)

1 . A compound, or a pharmaceutically acceptable salt thereof, having a structure of Formula (K):

wherein:

each R 1a , R 1b , R 1c , and R 1d is independently H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkoxyalkyl, halogen, C 1-6 haloalkyl, C 1-6 haloalkoxy, —NO 2 , or —CN;

alternatively, two R 1a groups on adjacent ring atoms are combined to form a C 4-8 cycloalkyl or 4 to 8 membered heterocycloalkyl having 1 to 2 heteroatoms, each independently N, O, or S;

R 2a and R 2b are each independently H, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, C 1-6 alkoxyalkyl, C 1-6 haloalkyl, or C 1-6 haloalkoxy;

alternatively, R 2a and R 2b are combined to form a 4 to 8 membered heterocycloalkyl having 1 to 2 heteroatoms, each independently N, O, or S;

R 3 is H, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkoxyalkyl, C 1-6 haloalkyl, or C 1-6 haloalkoxy;

R 3a is absent or C 1-6 alkyl;

alternatively, R 3 and R 3a are combined to form a 3 to 8 membered heterocycloalkyl having 1 to 2 heteroatoms, each independently N, O, or S;

subscripts m and p are each independently 0 to 2; and

subscripts n and r are each independently 0 to 3.

2 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having a structure of Formula (I):

3 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having a structure of Formula (Ia), Formula (Ib), Formula (Ic), or Formula (Id):

4 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1a is H, C 1-6 alkyl, C 1-6 alkoxy, or halogen.

5 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1a is H.

6 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2a and R 2b are each independently H, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxyalkyl, or C 1-6 haloalkyl.

7 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2a and R 2b are each independently C 1-6 alkyl.

8 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2a and R 2b are each independently ethyl.

9 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is H or C 1-6 alkyl.

10 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is methyl.

11 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having the following structure:

12 . The compound of claim 1 , having the following structure:

13 . The compound of claim 1 , or a pharmaceutically acceptable salt thereof, having the following structure:

14 . The compound of claim 1 , having the following structure:

15 . The compound of claim 1 , having the following structure:

16 . A crystalline compound of (7aS,10R)-10-(diethylcarbamoyl)-8,8-dimethyl-7a,8,9,10-tetrahydro-7H-indolo[7,1-fg][1,7]naphthyridin-8-ium iodide having the following structure:

characterized by unit cell dimensions of a=7.0716(6) Å, α=90°, b=14.4326(12) Å, β=90°, c=23.0876(19) Å, and γ=90°.

17 . A pharmaceutical composition, comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

18 . A method for increasing neural plasticity, the method comprising contacting a neuronal cell with a compound of claim 1 , or a pharmaceutically acceptable salt thereof, in an amount sufficient to increase neural plasticity of the neuronal cell, wherein the compound produces a maximum number of dendritic crossings with an increase of greater than 1.0 fold by a Sholl Analysis.

19 . A method for increasing neural plasticity and increasing dendritic spine density, the method comprising contacting a neuronal cell with a compound of claim 1 , or a pharmaceutically acceptable salt thereof, in an amount sufficient to increase neural plasticity and increase dendritic spine density of the neuronal cell.

Assignments (1)

Continuity (2)

References Cited (319)