IP Library › Granted Patent US 9,802,927

Granted Patent B2

US 9,802,927 · App. 15/178,626 · Granted Oct 31, 2017

Oxadiazine compounds and methods of use thereof

Inventors: Raksha Acharya (Bedford, MA); Duane A. Burnett (Wayland, MA); Matthew Gregory Bursavich (Needham, MA); Andrew Simon Cook (Stow, MA); Bryce Alden Harrison (Framingham, MA); Andrew J. McRiner (Melrose, MA)

Assignee: DENALI THERAPEUTICS, INC.

C07D413/14 A61K31/535 C07D247/02 C07D271/02 C07D273/02 C07D273/04 C07D413/04 C07D417/14 C07D471/04

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 9,802,927
App. No.: 15/178,626
Granted: Oct 31, 2017
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present disclosure relates to oxadiazine compounds, pharmaceutical compositions comprising an effective amount of an oxadiazine compound and methods for using an oxadiazine compound in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of an oxadiazine compound.

Claims (168)

1. A compound of Formula (I)

or a pharmaceutically acceptable salt thereof,

wherein:

R 1 is —C 1 -C 6 alkyl, —C 3 -C 8 monocyclic cycloalkyl, —C 1 -C 4 alkylene-C 3 -C 8 monocyclic cycloalkyl, phenyl, 5- to 6-membered aromatic heterocycle, 3- to 7-membered monocyclic heterocycle, 8- to 10-membered bicyclic heterocycle, each of which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of -halo, —CN, —C 1 -C 4 alkyl, —C 3 -C 8 monocyclic cycloalkyl, halo-substituted C 1 -C 4 alkyl, —C 1 -C 4 alkoxy, halo-substituted C 1 -C 4 alkoxy and oxo;

R 2 is hydrogen or —C 1 -C 4 alkyl;

Y is pyridinyl which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of -halo, —C 1 -C 4 alkoxy, halo-substituted C 1 -C 4 alkoxy, —C 1 -C 4 alkyl, halo-substituted C 1 -C 4 alkyl, —CN and —OH; and

Z is nitrogen-containing 3- to 7-membered monocyclic heterocycle which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of -halo, —C 1 -C 4 alkyl, halo-substituted C 1 -C 4 alkyl, —C 1 -C 4 alkoxy and —OCF 3 .

2. A compound of claim 1 , wherein R 1 is —C 1 -C 6 alkyl, —C 3 -C 8 monocyclic cycloalkyl, phenyl, 8- to 10-membered bicyclic heterocycle, each of which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of -halo, —CN, —C 1 -C 4 alkyl, —C 3 -C 8 monocyclic cycloalkyl, halo-substituted C 1 -C 4 alkyl, —C 1 -C 4 alkoxy and halo-substituted C 1 -C 4 alkoxy; or a pharmaceutically acceptable salt thereof.

3. A compound of claim 1 , wherein R 1 is —C 3 -C 8 monocyclic cycloalkyl, phenyl, 8- to 10-membered bicyclic heterocycle, each of which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of -halo, —C 1 -C 4 alkyl, —C 3 -C 8 monocyclic cycloalkyl, halo-substituted C 1 -C 4 alkyl, and halo-substituted C 1 -C 4 alkoxy; or a pharmaceutically acceptable salt thereof.

4. A compound of claim 1 , wherein R 1 is 8- to 10-membered bicyclic heterocycle, each of which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of -halo, —C 1 -C 4 alkyl, and halo-substituted C 1 -C 4 alkyl; or a pharmaceutically acceptable salt thereof.

5. A compound of claim 1 , wherein R 1 is phenyl, each of which is unsubstituted or substituted with one or more substituents independently selected from the group consisting of -halo, —CN, —C 1 -C 4 alkyl, —C 3 -C 8 monocyclic cycloalkyl, halo-substituted C 1 -C 4 alkyl, —C 1 -C 4 alkoxy and halo-substituted C 1 -C 4 alkoxy; or a pharmaceutically acceptable salt thereof.

6. A compound of claim 1 , wherein R 1 is —C 1 -C 6 alkyl which is unsubstituted; or a pharmaceutically acceptable salt thereof.

7. A compound of claim 1 , wherein R 1 is —C 3 -C 8 monocyclic cycloalkyl, each of which is unsubstituted or substituted with one or more -halo; or a pharmaceutically acceptable salt thereof.

8. A compound of claim 1 , wherein R 1 is —C 3 -C 8 monocyclic cycloalkyl which is unsubstituted; or a pharmaceutically acceptable salt thereof.

9. A compound of claim 1 , wherein Y is pyridinyl which is unsubstituted or substituted with one or more —C 1 -C 4 alkoxy, halo-substituted C 1 -C 4 alkoxy; or a pharmaceutically acceptable salt thereof.

10. A compound of claim 1 , wherein Z is nitrogen-containing 3- to 7-membered monocyclic heterocycle which is unsubstituted or substituted with one or more —C 1 -C 4 alkyl; or a pharmaceutically acceptable salt thereof.

11. A compound of claim 1 , wherein Z is imidazolyl which is unsubstituted or substituted with one methyl; or a pharmaceutically acceptable salt thereof.

12. A compound of claim 1 , wherein:

R 1 is

each of which is optionally further substituted with -halo, —CF 3 or —C 1 -C 4 alkyl; and

Z is

or a pharmaceutically acceptable salt thereof.

13. The compound of claim 12 , wherein Y is

wherein the left most radical is connected to the Z group in Formula (I); or a pharmaceutically acceptable salt thereof.

14. A compound selected from the group consisting of:

(R)-5-(benzofuran-2-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5, 6-dihydro-4H-1,2,4-oxadiazine;

3-(6-Methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5-(7-methylbenzofuran-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(R)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5-(5-methylbenzofuran-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(R)-5-(benzo[b]thiophen-2-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5-(3-methylbenzofuran-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(R)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5-(4-methylbenzofuran-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(R)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5-(6-methylbenzofuran-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methyl-5-(7-methylbenzofuran-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(5-(4-chloro-1H-imidazol-1-yl)-6-methoxypyridin-2-yl)-5-(7-methylbenzofuran-2-yl)-5, 6-dihydro-4H-1,2,4-oxadiazine;

5-(4-chloro-2-methylphenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-4-methyl-5,6-dihydro-4H-1,2,4-oxadiazine;

3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-4-methyl-5-(3-(trifluoromethyl) phenyl)-5, 6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methoxy-1H-imidazol-1-yl)pyridin-2-yl)-5-(7-methylbenzofuran-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5-phenyl-5,6-dihydro-4H-1,2,4-oxadiazine;

5-(benzofuran-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

5-(4-fluorophenyl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl)pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

5-(4-chlorophenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

5-(4-fluoro-3-(trifluoromethyl)phenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

5-(1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(3, 4-dichlorophenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(6-fluorobenzofuran-2-yl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(4-methoxyphenyl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(5-chlorobenzofuran-2-yl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(4-(trifluoromethyl) phenyl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-cyclohexyl-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(7-chlorobenzofuran-2-yl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(3-methylbenzo [b] thiophen-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(benzo [b] thiophen-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(4-(trifluoromethoxy) phenyl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-(5-chloro-1-ethyl-6-fluoro-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(5-chloro-1-ethyl-6-fluoro-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(3,4-difluorophenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(6-chlorobenzofuran-2-yl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(3,5-difluorophenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(5-fluorobenzofuran-2-yl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(4-chloro-3-methylphenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(7-fluorobenzofuran-2-yl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(3,4,5-trifluorophenyl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(4-(difluoromethoxy) phenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(4-chlorobenzofuran-2-yl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-(4-fluorobenzofuran-2-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(5-fluoro-3-methylbenzofuran-2-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-(6-fluoro-1-methyl-5-(trifluoromethyl)-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(6-fluoro-1-methyl-5-(trifluoromethyl)-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(4-chloro-3-fluorophenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(3-chloro-4-fluorophenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(3-chloro-5-fluorophenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(3-(trifluoromethyl) phenyl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(4-cyclopropylphenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(3,5-dichlorophenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(3-fluoro-4-(trifluoromethyl) phenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(1-methyl-1H-indazol-3-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(3-cyclopropylphenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

5-(2,4-difluorophenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(o-tolyl)-5,6-dihydro-4H-1,2,4-oxadiazine;

5-(2-chlorophenyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine:

(+)-5-(4, 4-difluorocyclohexyl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazin-5-yl) benzonitrile;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(3-methoxyphenyl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-(tert-butyl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-isobutyl-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-cyclopentyl-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5-(1-methyl-1H-indol-3-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5-(1-methyl-1H-indol-3-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(5-fluoro-1-methyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(4-fluoro-1-methyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-(4-fluoro-1-methyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-(6-fluoro-1-methyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(6-fluoro-1-methyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-(5-chloro-1-methyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(5-chloro-1-methyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(6-chloro-1-methyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-(6-chloro-1-methyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(1-methyl-1H-pyrrolo [2,3-b]pyridin-3-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-5-(4-fluoro-1-isopropyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-5-(4-fluoro-1-isopropyl-1H-indol-3-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(1-methyl-6-(trifluoromethyl)-1H-indol-3-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(−)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(1-methyl-6-(trifluoromethyl)-1H-indol-3-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methyl-5-(1-methyl-1H-indol-3-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-2-(3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazin-5-yl)benzo[d]oxazole;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5-(1-methyl-1H-indol-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

(+)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl) pyridin-2-yl)-5-(1-methyl-5-(trifluoromethyl)-1H-pyrrolo [2,3-b] pyridin-3-yl)-5,6-dihydro-4H-1,2,4-oxadiazine; and

(+)-5-(benzo[d]thiazol-2-yl)-3-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-5,6-dihydro-4H-1,2,4-oxadiazine;

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 14 , selected from the group consisting of: