ABHD12 inhibitors and methods of making and using same

Patent metadata

Field	Value
Publication number	US-11897865-B2
Application number	US-201917055081-A
Country	US
Kind code	B2
Filing date	May 14, 2019
Priority date	May 15, 2018
Publication date	Feb 13, 2024
Grant date	Feb 13, 2024

Abstract

Provided herein are compounds and compositions useful as modulators of ABHD12. Furthermore, the subject compounds and compositions are useful as immunotherapies in treating, for instance, cancer or infectious diseases.

First claim

What is claimed is:

1. A compound of Formula (I):

wherein:
each R 1 is independently selected from halogen, —CN, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, C 1-6 haloalkyl, —C(O)R 2 , —OR 3 , and phenyl optionally substituted with 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy;
each R 2 is independently C 1-6 alkyl;
each R 3 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, -C 1-6 alkyl-C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, phenyl, and -C 1-6 alkyl-phenyl, wherein C 3-6 cycloalkyl, -C 1-6 alkyl-C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, phenyl, and -C 1-6 alkyl-phenyl are optionally substituted with 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, and —C(O)OR 4 ;
each R 4 is independently C 1-6 alkyl; and
n is 0, 1, 2, or 3;
or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof.

2. A compound of Formula (II):

wherein:
each R 1 is independently selected from halogen, —CN, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkynyl, C 1-6 haloalkyl, —C(O)R 2 , —OR 3 , and phenyl optionally substituted with 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy;
each R 2 is independently C 1-6 alkyl;
each R 3 is independently selected from H, C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, -C 1-6 alkyl-C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, phenyl, and -C 1-6 alkyl-phenyl, wherein C 3-6 cycloalkyl, -C 1-6 alkyl-C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, phenyl, and -C 1-6 alkyl-phenyl are optionally substituted with 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, and —C(O)OR 4 ;
each R 4 is independently C 1-6 alkyl;
R 5 is selected from halogen, —CN, C 1-6 alkenyl, C 1-6 alkynyl, C 1-6 haloalkyl, —C(O)R 2 , —OR 3 , and phenyl optionally substituted with 1, 2, or 3 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy; and
n is 0, 1, 2, or 3;
or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof.

3. The compound of claim 2 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein R 5 is selected from halogen, —CN, C 1-6 alkynyl, C 1-6 haloalkyl, —C(O)R 2 , —OR 3 , and phenyl optionally substituted with 1 or 2 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy.

4. The compound of claim 3 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein R 5 is selected from halogen, C 1-6 haloalkyl, —OR 3 , and phenyl substituted with 1 or 2 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy.

5. The compound of claim 1 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from halogen, —CN, C 1-6 alkyl, C 1-6 alkynyl, C 1-6 haloalkyl, —C(O)R 2 , —OR 3 , and phenyl optionally substituted with 1 or 2 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy.

6. The compound of claim 5 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein each R 1 is independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, —OR 3 , and phenyl substituted with 1 or 2 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy.

7. The compound of claim 1 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein each R 3 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, -C 1-6 alkyl-C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, phenyl, and -C 1-6 alkyl-phenyl, wherein C 3-6 cycloalkyl, -C 1-6 alkyl-C 3-6 cycloalkyl, C 2-9 heterocycloalkyl, phenyl, and -C 1-6 alkyl-phenyl are optionally substituted with 1 or 2 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, and C(O)OR 4 .

8. The compound of claim 7 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein each R 3 is independently selected from C 1-6 alkyl, C 1-6 haloalkyl, phenyl, and -C 1-6 alkyl-phenyl, wherein phenyl and -C 1-6 alkyl-phenyl are optionally substituted with 1 or 2 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, and C 1-6 haloalkoxy.

9. The compound of claim 8 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein R 3 is C 1-6 haloalkyl, phenyl, or -C 1-6 alkyl-phenyl, wherein phenyl or -C 1-6 alkyl-phenyl are optionally substituted with 1 or 2 substituents independently selected from halogen, C 1-6 haloalkyl, and C 1-6 haloalkoxy.

10. The compound of claim 1 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein n is 1, 2, or 3.

11. The compound of claim 10 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein n is 1 or 2.

12. The compound of claim 11 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein n is 1.

13. The compound of claim 11 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, wherein n is 2.

14. The compound of claim 2 , selected from:

or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof.

15. The compound of claim 1 , selected from:

or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof.

16. A compound selected from:

or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof.

17. A pharmaceutical composition comprising a compound of claim 1 , or a solvate, N-oxide, stereoisomer, or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

18. A method of in

Assignees

• Scripps Research Inst

Inventors

• Ogasawara Daisuke
• Ichu Taka-Aki
• Hulce Jonathan
• Cravatt Benjamin F

Classifications

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D471/08

  Bridged systems · CPC title