Granted Patent B2

US 12,637,413 · App. 18/558,726 · Granted May 26, 2026

Inventors: Brian Andrew Stearns (San Diego, CA); Jill Melissa Baccei (San Diego, CA); Jason Randall Harris (San Diego, CA)

Assignee: AUTOBAHN THERAPEUTICS, INC.

C07C235/20A61K31/16A61K31/165A61K31/397A61K31/40A61K31/42A61K31/44A61K31/4406A61K31/4409A61K31/455A61K31/4965A61K31/50A61K31/505A61K31/5375A61P25/00C07C235/16C07C235/22C07C235/24C07C243/28C07C255/29C07C259/06C07C313/02C07C317/28C07D205/04C07D213/75C07D237/20C07D237/22C07D239/42C07D241/20C07D261/14C07D295/18C07D305/08C07C2601/02C07C2601/14

Abstract

Claims (27)

1 . A pharmaceutical composition comprising a fatty acid amide hydrolase (FAAH) cleavable prodrug of Formula (I′), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

R 1 and R 2 are independently selected from hydrogen, —OR 5 , —NR 5 R 6 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 heterocycloalkyl, phenyl, and —C 1 -C 6 alkyl-phenyl, wherein C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 6 cycloalkyl, C 3 -C 6 heterocycloalkyl, phenyl, and —C 1 -C 6 alkyl-phenyl are optionally substituted with one or more of halo, cyano, —OR 5 , —NR 5 R 6 , —S(O) 2 R 5 , or —S(O) 2 OR 5 ;

R 3 and R 4 are independently selected from —F, —Cl, —Br, and —I;

R 5 and R 6 are independently selected from hydrogen and C 1 -C 6 alkyl; and

R 7 and R 8 are independently selected from hydrogen, —F, —Cl, —Br, and —I;

and a pharmaceutically acceptable excipient; further comprising a peripherally restricted FAAH inhibitor.

2 . The pharmaceutical composition of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 7 is hydrogen.

3 . The pharmaceutical composition of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 7 is —F.

4 . The pharmaceutical composition of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 8 is hydrogen.

5 . The pharmaceutical composition of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 8 is —F.

6 . The pharmaceutical composition of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is hydrogen.

7 . The pharmaceutical composition of claim 6 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is C 1 -C 6 alkyl optionally substituted with one or more of halo, cyano, —OR 5 , —NR 5 R 6 , —S(O) 2 R 5 , or —S(O) 2 OR 5 .

8 . The pharmaceutical composition of claim 7 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is C 1 -C 6 alkyl substituted with one or more of halo, cyano, —OR 5 , —NR 5 R 6 , —S(O) 2 R 5 , or —S(O) 2 OR 5 .

9 . The pharmaceutical composition of claim 8 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is C 1 -C 6 alkyl substituted with one or more-OH.

10 . The pharmaceutical composition of claim 8 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is C 1 -C 6 alkyl substituted with one or more of halo.

11 . The pharmaceutical composition of claim 7 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is unsubstituted C 1 -C 6 alkyl.

12 . The pharmaceutical composition of claim 6 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is phenyl optionally substituted with one or more of halo, cyano, —OR 5 , —NR 5 R 6 , —S(O) 2 R 5 , or —S(O) 2 OR 5 .

13 . The pharmaceutical composition of claim 6 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 2 is —C 1 -C 6 alkyl-phenyl optionally substituted with one or more of halo, cyano, —OR 5 , —NR 5 R 6 , —S(O) 2 R 5 , or —S(O) 2 OR 5 .

14 . The pharmaceutical composition of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 and R 4 are independently selected from —F, —Cl, —Br.

15 . The pharmaceutical composition of claim 14 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 and R 4 are both —Br.

16 . The pharmaceutical composition of claim 14 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 3 and R 4 are both —Cl.

17 . The pharmaceutical composition of claim 1 , wherein the fatty acid amide hydrolase (FAAH) cleavable prodrug of Formula (I′) has a structure selected from:

or a pharmaceutically acceptable salt or solvate thereof.

18 . The pharmaceutical composition of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein the peripherally restricted FAAH inhibitor is ASP-3652.

19 . A method of treating a CNS disease or disorder in a patient in need thereof comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition of claim 1 , or a pharmaceutically acceptable salt or solvate thereof.

20 . The method of claim 19 , wherein the CNS disease or disorder is selected from acute disseminated encephalomyelitis (ADEM), acute hemorrhagic leukoencephalitis (AHL or AHLE), adult Refsum disease, infantile Refsum disease, Alexander disease, Alzheimer's disease, Balo concentric sclerosis, Canavan disease, central pontine myelinolysis (CPM), cerebral palsy, cerebrotendineous xanthomatosis, chronic inflammatory demyelinating polyneuropathy (CIDP), Devic's syndrome, diffuse myelinoclastic sclerosis, encephalomyelitis, Guillain-Barre syndrome, idiopathic inflammatory demyelinating disease (HDD), Krabbe disease, Leber hereditary optic neuropathy, leukodystrophy, Marburg multiple sclerosis, Marchiafava-Bignami disease, metachromatic leukodystrophy (MLD), multifocal motor neuropathy (MMN), multiple sclerosis (MS), paraproteinemic demyelinating polyneuropathy, Pelizaeus-Merzbacher disease (PMD), progressive multifocal leukoencephalopathy (PML), tropical spastic paraparesis (TSP), X-linked adrenoleukodystrophy (X-ALD, ALO, or X-linked ALO), and Zellweger syndrome.

Assignments (1)

Continuity (3)

References Cited (216)