Granted Patent B2

US 12,269,800 · App. 18/405,058 · Granted Apr 8, 2025

Inventors: Jacob M. Hooker (Winchester, MA); Michael S. Placzek (Boston, MA)

Assignee: Sensorium Therapeutics, Inc.

C07D209/12C07D401/12C07D405/12C07D409/12C07D475/04C07D491/113C07D491/20C07D495/04C07D495/10C07D497/10C07D498/10C07D519/00C07F7/1804

Abstract

Claims (45)

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein

R 1 is or C 1 -C 7 alkyl or H; and

ring A is

wherein * denotes the attachment points of ring A to the compound of formula (I), and wherein

each of W and Z is independently O, NH, or S;

each R 2 is independently C 1 -C 3 alkyl, C 2 -C 6 alkenyl, —COOH, —CONH 2 , C 3 -C 10 cycloalkyl, phenyl, 5- to 7-membered heterocyclyl, or 5- to 7-membered heteroaryl, wherein each hydrogen atom in C 1 -C 3 alkyl, C 2 -C 6 alkenyl, phenyl, 5- to 7-membered heterocyclyl and 5- to 7-membered heteroaryl is optionally substituted by —OH, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, aryloxy, C 1 -C 3 alkanol, or —NO 2 , wherein each hydrogen atom in C 1 -C 3 alkoxy and aryloxy is optionally substituted by C 1 -C 3 alkoxy or phenyl; or two R 2 s on a single carbon atom combine to form ═O; or two adjacent R 2 s together with the carbon atoms to which they are attached combine to form 5- to 7-membered heteroaryl or phenyl, wherein each hydrogen atom in 5- to 7-membered heteroaryl or phenyl is optionally substituted by —OH, C 1 -C 3 alkyl, or C 1 -C 3 alkanol;

m is 1 or 2;

n is 0, 1, 2, or 3;

R 3 is —OSi (C 1 -C 6 alkyl) 3, —OC(O)C 2 -C 6 alkenyl, —OC(O)C 3 -C 10 cycloalkyl, —OC(O)phenyl, —OC(O)-5- to 7-membered heteroaryl, wherein each hydrogen atom in C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 10 cycloalkyl, phenyl, and 5- to 7-membered heteroaryl is optionally substituted by halogen, C 1 -C 6 alkyl, C 1 -C 3 alkoxy, nitro, —N(C 1 -C 3 alkyl) 2, C 1 -C 3 haloalkyl, cyano, phenyl, phenoxy or —O(CH 2 ) p OCH 3 ;

p is 2, 3, or 4;

R 4 is —OR 5 or —N(R 5 ) 2;

each R 5 is H, C 1 -C 6 alkyl, C 3 -C 6 heterocycloalkyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, phenyl, 5- to 10-membered heteroaryl, —C(O)-5- to 7-membered heteroaryl, —C(O)—C 1 -C 8 alkyl, —C(O)—C 3 -C 10 cycloalkyl, —C(O)-phenyl, —C(O)N(H)-phenyl, —C(O)N(H)-5- to 7-membered heteroaryl, —C(O)N(H)—C 1 -C 6 alkyl, —C(O)C(O)OH, or —CONH 2 , wherein each hydrogen atom in C 1 -C 6 alkyl, C 3 -C 6 heterocycloalkyl, C 3 -C 10 cycloalkyl, C 1 -C 6 alkoxy, phenyl, 5- to 10-membered heteroaryl, —C(O)-5- to 7-membered heteroaryl, —C(O)—C 1 -C 8 alkyl, —C(O)—C 3 -C 10 cycloalkyl, —C(O)-phenyl, —C(O)N(H)-phenyl, —C(O)N(H)-5- to 7-membered heteroaryl, and —C(O)N(H)—C 1 -C 6 alkyl is optionally substituted by halogen, OH, C 1 -C 3 alkyl, C 3 -C 10 cycloalkyl optionally substituted by —COOH, phenyl, 5- to 7-membered heteroaryl, aryloxy, C 1 -C 6 alkoxy, C 1 -C 3 alkanol, C 3 -C 6 heterocycloalkyl optionally substituted with methyl, —COOH, —S(O) 2CH 3 , —C(O)C 1 -C 6 alkyl, or —C(O) OC 1 -C 6 alkyl; and

each of R 6 and R 7 is independently C 1 -C 3 alkyl;

provided the compound of Formula (I) is not

2. The compound of claim 1 , wherein R 1 is methyl.

3. The compound of claim 2 , wherein ring A is

4. The compound of claim 3 , wherein R 3 is —OC(O)C 2 -C 6 alkenyl, —OC(O)C 3 -C 6 cycloalkyl, —OC(O)phenyl, —OC(O)-5- to 6-membered heteroaryl, wherein each hydrogen atom in C 2 -C 6 alkenyl, C 3 -C 10 cycloalkyl, phenyl, and 5- to 6-membered heteroaryl is optionally substituted by halogen, C 1 -C 6 alkyl, C 1 -C 3 alkoxy, nitro, —N(C 1 -C 3 alkyl) 2, C 1 -C 3 haloalkyl, or cyano.

5. The compound of claim 4 , wherein R 3 is —OC(O)C 3 -C 6 cycloalkyl.

6. The compound of claim 4 , wherein R 3 is —OC(O)-5- to 6-membered heteroaryl, wherein each hydrogen atom in the 5- to 6-membered heteroaryl is optionally substituted by halogen, C 1 -C 6 alkyl, C 1 -C 3 alkoxy, nitro, —N(C 1 -C 3 alkyl) 2, C 1 -C 3 haloalkyl, or cyano.

7. The compound of claim 4 , wherein R 3 is —OC(O)phenyl, wherein each hydrogen atom in the phenyl is optionally substituted by halogen, C 1 -C 6 alkyl, C 1 -C 3 alkoxy, nitro, —N(C 1 -C 3 alkyl) 2, C 1 -C 3 haloalkyl, or cyano.

8. The compound of claim 7 , wherein R 3 is —OC(O)phenyl, wherein each hydrogen atom in the phenyl is optionally substituted by C 1 -C 6 alkyl.

9. The compound of claim 1 , wherein the compound is a compound of formula (IIIb-1)

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is methyl; and

R 3 is —OC(O)C 2 -C 6 alkenyl, —OC(O)C 3 -C 6 cycloalkyl, —OC(O)phenyl, or —OC(O)-(5- or 6-membered heteroaryl), wherein each hydrogen atom in the phenyl, and 5- or 6-membered heteroaryl is optionally substituted by halogen, C 1 -C 6 alkyl, C 1 -C 3 alkoxy, nitro, —N(C 1 -C 3 alkyl) 2, C 1 -C 3 haloalkyl, or cyano.

10. The compound of claim 9 , wherein R 3 is unsubstituted cyclohexyl or unsubstituted cyclopropyl.

11. The compound of claim 9 , wherein the R 3 is isopropenyl or butenyl.

12. The compound of claim 9 , wherein R 3 is —OC(O)-6-membered heteroaryl, and the 6-membered heteroaryl is unsubstituted pyridyl.

13. The compound of claim 9 , wherein R 3 is —OC(O)phenyl, optionally substituted by halogen, C 1 -C 6 alkyl, C 1 -C 3 alkoxy, nitro, —N(C 1 -C 3 alkyl) 2, C 1 -C 3 haloalkyl, or cyano.

14. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

15. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

16. The compound of claim 1 , wherein the compound is

or a pharmaceutically acceptable salt thereof.

17. A compound of formula (IIIb-1)

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is methyl; and

R 3 is —OC(O)C 2 -C 6 alkenyl, —OC(O)C 3 -C 6 cycloalkyl, —OC(O)phenyl, or —OC(O)-(5- or 6-membered heteroaryl), wherein each hydrogen atom in the alkenyl, cycloalkyl, phenyl, or 5- or 6-membered heteroaryl is optionally substituted by halogen, C 1 -C 6 alkyl, nitro, amino, alkylamino, C 1 -C 3 haloalkyl, or cyano.

18. The compound of claim 17 , wherein R 3 is —OC(O)phenyl, wherein each hydrogen atom in the phenyl is optionally substituted by one or more chloro, fluoro, C 1 -4 alkyl optionally substituted by one or more fluoro, methoxy, nitro, —N(CH 3 ) 2 , or cyano.

19. The compound of claim 17 , wherein R 3 is —OC(O)pyridinyl, wherein each hydrogen atom in the pyridinyl is optionally substituted by one or more C 1 -4 alkyl.

20. The compound of claim 1 , selected from the group consisting of:

or a compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

Assignments (1)

Continuity (4)

References Cited (150)