Granted Patent B2

US 12,358,929 · App. 18/368,244 · Granted Jul 15, 2025

Inventors: David R. Anderson (Salem, CT); Robert A. Volkmann (Mystic, CT); Frank S. Menniti (Mystic, CT); Christopher Fanger (Bolton, MA); Yuelian Xu (East Haven, CT)

Assignee: Novartis AG

C07D513/04C07D471/04C07D487/04C07D495/04C07D498/04C07D513/20

Abstract

Claims (24)

1. A compound of the Formula Ic:

or a pharmaceutically acceptable salt thereof, wherein

R 1 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-6 cycloalkyl, —C(O)OH, —C(O)OC 1-6 alkyl, (C 3-6 ) cycloalkyl and phenyl (optionally substituted by one, two or three substituents each selected from halogen, C 1-6 alkyl, C 1-6 alkoxy, —C(O)OH, —C(O)OC 1-6 alkyl and NR a R b );

R 4 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, —CO 2 H, —CO 2 C 1-6 alkyl, —CO 2 NR a R b , NR a R b , C 3-6 cycloalkyl and phenyl (optionally substituted by one or two substituents each selected from halogen or methyl);

R 5 independently for each occurrence is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 alkoxy, halogen, cyano, OH, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, heteroaryl, phenyl, —NR a R b , —C(O)OH, C 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, (NR a R b ) carbonyl-, C 1-6 alkyl-S(O) w — (where w is 0, 1 or 2), and R a R b N—SO w — (where w is 0, 1 or 2); wherein heteroaryl and phenyl may optionally be substituted by one, two or three substituents each selected from the group consisting of halogen, cyano, C 1-6 alkyl, C 1-6 alkoxy, and —NR a R b ; wherein one or more carbon atoms of said C 3-6 cycloalkyl may be optionally replaced by N or O; or two R 5 , together with two adjacent carbons on ring A to which they are attached, form a 5-7 membered unsaturated, partially unsaturated or saturated carbocyclic or heterocyclic ring;

R 6 for each occurrence is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 3-6 cycloalkyl, —C(O)—C 1-6 alkyl, and phenyl (optionally substituted by one or two substituents each selected from halogen or methyl);

Ring A is pyridinyl, pyrimidinyl or pyridazinyl;

R C is selected from the group consisting of cyano, hydrogen, halogen, S(C 1-6 ) alkyl, S(O)(C 1-6 ) alkyl, SO 2 (C 1-6 )alkyl, C(O)NR a R b , —C(O)OH, —C(O)O(C 1-6 )alkyl, (C 1-6 )alkyl, (C 2-6 ) alkenyl, (C 2-6 ) alkynyl and heteroaryl (optionally substituted by C 1-4 alkyl or halogen);

R a and R b are independently selected, for each occurrence, from the group consisting of: hydrogen, C 1-4 alkylcarbonyl, C 1-6 alkoxycarbonyl, cyclopropyl, and C 1-3 alkyl; wherein C 1-3 alkyl may optionally be substituted on a carbon not bound to the nitrogen by one or more substituents each selected from the group consisting of fluorine, cyano, oxo and hydroxyl; or R a and R b , together with the nitrogen to which they are attached, form a 4-6 membered heterocyclic ring which may have an additional heteroatom selected from O, S, or N (optionally substituted by one or two methyl groups); and wherein the 4-6 membered heterocyclic ring may optionally be substituted on a carbon not bound to the nitrogen by one or more substituents; and

p is 0, 1, 2 or 3.

2. The compound of claim 1 , wherein R 5 is independently for each occurrence selected from the group consisting of hydrogen, halogen, methoxy, methyl, ethyl, propyl, isopropyl, cyclopropyl, t-butyl, t-butyloxy, t-butylthio, pyridinyl (optionally substituted by halogen), and phenyl (optionally substituted by halogen).

3. The compound of claim 1 , wherein R 5 is t-butyl.

4. The compound of claim 1 , wherein Re is-CN.

5. The compound of claim 1 , wherein p is 1.

6. The compound of claim 1 , wherein p is 2.

7. The compound of claim 1 , wherein R 4 is selected from the group consisting of hydrogen, C 1-4 alkyl, and phenyl.

8. The compound of claim 1 , wherein R 4 is hydrogen.

9. The compound of claim 1 , wherein R 1 is selected from the group consisting of hydrogen, (C 1-6 ) alkyl, (C 2-6 ) alkenyl, (C 2-6 ) alkynyl, (C 3-6 ) cycloalkyl and phenyl (optionally substituted by one or two substituents each selected from halogen or methyl), t is 0, 1 or 2.

10. The compound of claim 1 , wherein R 1 is hydrogen.

11. A pharmaceutically acceptable composition comprising a compound according to claim 1 , and a pharmaceutically acceptable excipient.

12. A method of treating a patient suffering from a neuropsychiatric disorder comprising administering a compound according to claim 1 , to the patient.

13. The method according to claim 12 , wherein the neuropsychiatric disorder is selected from schizophrenia, depression, an autism spectrum disorder, and Rett syndrome.

14. A compound, wherein the compound is selected from:

or a pharmaceutically acceptable salt of any of the foregoing.

Assignments (2)

Continuity (6)

References Cited (167)