Bicyclic pyridine derivative
The present disclosure provides bicyclic pyridine derivatives. A compound represented by formula I: or a pharmaceutically acceptable salt thereof, wherein X is a oxygen atom, sulfur atom, NR, or CR′R″, n is 0 or 1, R 1 , R 2a , R 2b , R 2c , R 2d , R, R′ and R″ are each independently a hydrogen atom, a halogen atom, optionally substituted C 1-6 alkyl, or an optionally substituted C 6-10 aryl, or two of R 2a , R 2b , R 2c , R 2d , R, R′, and R″, together with a carbon atom or a nitrogen atom to which they are attached, form a 3- to 6-membered saturated carbocyclic ring or saturated heterocyclic ring, and R 3a , R 3b , R 3c and R 5a and R 5b , are as defined in the description.
1. A compound selected from the group consisting of:
1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine;
1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine;
N-methyl-1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine;
1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-methylmethanamine; and
1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-(2H3)methylmethanamine,
or a pharmaceutically acceptable salt thereof.
2. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
3. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is 1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
4. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is N-methyl-1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
5. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-methylmethanamine.
6. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-(2H3)methylmethanamine.
7. A pharmaceutical composition, comprising:
a compound or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient or additive, wherein the compound is selected from the group consisting of:
1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine;
1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine;
N-methyl-1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine;
1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-methylmethanamine; and
1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-(2H3)methylmethanamine.
8. The pharmaceutical composition according to claim 7 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
9. The pharmaceutical composition according to claim 7 , wherein the compound is 1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
10. The pharmaceutical composition according to claim 7 , wherein the compound is N-methyl-1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
11. The pharmaceutical composition according to claim 7 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-methylmethanamine.
12. The pharmaceutical composition according to claim 7 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-(2H3)methylmethanamine.
13. A method for treating a neurological or psychiatric disorder in a subject, comprising:
administering to the subject a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof,
wherein the neurological or psychiatric disorder is depression, bipolar disorder, schizophrenia, obsessive-compulsive disorder, addiction, social disorder, attention deficit/hyperactivity disorder, anxiety disorder, movement disorder, epilepsy, autism, cognitive dysfunction, psychosis in Alzheimer's disease/Parkinson's disease, irritation/aggression of Parkinson's disease, mood disorders, irritation, agitation, or aggression associated with Alzheimer's disease or hyperphagia.
14. The method according to claim 13 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
15. The method according to claim 13 , wherein the compound is 1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
16. The method according to claim 13 , wherein the compound is N-methyl-1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
17. The method according to claim 13 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-methylmethanamine.
18. The method according to claim 13 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-(2H3)methylmethanamine.
19. The method according to claim 13 , wherein the neurological or psychiatric disorder is depression, schizophrenia, obsessive-compulsive disorder, anxiety disorder, psychosis in Alzheimer's disease/Parkinson's disease, mood disorders, or irritation, agitation, or aggression associated with Alzheimer's disease.
20. The method according to claim 19 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
21. The method according to claim 19 , wherein the compound is 1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
22. The method according to claim 19 , wherein the compound is N-methyl-1-[(2R,3S)-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]methanamine.
23. The method according to claim 19 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-methylmethanamine.
24. The method according to claim 19 , wherein the compound is 1-[(2R,3S)-6-fluoro-2-methyl-2,3-dihydrofuro[3,2-b]pyridin-3-yl]-N-(2H3)methylmethanamine.
25. The method according to claim 13 , wherein the neurological or psychiatric disorder is depression, schizophrenia, psychosis in Alzheimer's disease, or irritation, agitation, or aggression associated with Alzheimer's disease.