Heterocyclic compounds for the treatment of neurological and psychological disorders
Lactam compounds of Formula I and their use for the treatment of neurological and psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorder and insomnia is disclosed.
1. A method of treating a psychiatric disorder in a subject in need thereof, comprising administering to the subject a compound having the Formula:
or pharmaceutically acceptable salts and solvates thereof:
wherein,
represents a single or double bond;
A is selected from the group consisting of absent, alkyl, alkenyl, alkynyl, —S—, —O—, —S(O)—, S(O) 2 —, —S[C(R 10 )(R 11 )] u —, —S(O) [C(R 10 )(R 11 )] u —, —S(O) 2 [C(R 10 )(R 11 )] u —, —O[C(R 10 )(R 11 )] u —, —N(R 10 )—, —N(R 10 )—[C(R 10 )(R 11 )] u —, and —[C(R 10 )(R 11 )] u ;
D is selected from the group consisting of absent, —O—, —NR 10 , —C(R 10 )(R 11 )—, —S—, S(O)—, —S(O) 2 —, and —C(O)—;
X 2 is —S— or —O—;
each G 3 and G 4 is independently —N— or —C(R 10 )—[C(R 10 )(R 11 )] a —,
R 2 selected from the group consisting of absent, hydrogen, halogen, —OR 10 , —SR 10 , —N(R 10 )(R 11 ), —S(O)R 10 , —S(O) 2 R 10 , aliphatic, aryl and heterocyclyl;
each R 3 and R 4 is independently selected from the group consisting of absent, hydrogen, halogen, —OR 10 , —SR 10 , —N(R 10 )(R 11 ), —S(O)R 10 , —S(O) 2 R 10 , aliphatic, aryl, and heterocyclyl; or
alternatively, two R 3 and R 4 together form an optionally substituted ring;
R 5 is selected from the group consisting of —CH(R 10 )—OR 20 , —CH(R 10 )—OC(O)OR 20 , —CH(R 10 )—OC(O)R 20 , —CH(R 10 )—OC(O)NR 20 R 21 , —(CH(R 10 ))—OPO 3 MY, —(CH(R 10 ))—OP(O)(OR 20 )—(OR 21 ), —[CH(R 10 )O] z —R 20 , —[CH(R 10 )O] z —C(O)OR 20 , —[CH(R 10 )O] z —C(O)R 20 , —[CH(R 10 )O] z —C(O)NR 20 R 21 , —[CH(R 10 )O] z —OPO 3 MY, —[CH(R 10 )O] z —P(O) 2 (OR 20 )M and —[CH(R 10 )O] z —P(O)(OR 20 )(OR 21 );
each R 10 and R 11 is independently absent, hydrogen, halogen, aliphatic, or aryl;
each R 20 and R 21 is independently selected from hydrogen, aliphatic, or aryl;
Y and M are the same or different and each is a monovalent cation; or M and Y together is a divalent cation;
z and u are independently 1, 2, 3, 4, 5, 6 or 7;
a, m, and q are independently selected from 0, 1, and 2;
r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11; and
wherein the psychiatric disorder is selected from the group consisting of schizophrenia, bipolar disorder, depression, mania, and anxiety.
2. The method of claim 1 , wherein the compound of Formula VIII is a compound having the Formula:
or pharmaceutically acceptable salts and solvates thereof.
3. The method of claim 2 , wherein the compound of Formula IX is a compound having the Formula:
or pharmaceutically acceptable salts and solvates thereof.
4. The method of claim 1 , wherein R 5 is selected from the group consisting of
5. The method of claim 3 , wherein the compound of Formula X is selected from the group consisting of
6. The method of claim 1 , wherein the psychiatric disorder is schizophrenia.
7. The method of claim 5 , wherein the psychiatric disorder is schizophrenia.
8. The method of claim 1 , wherein the psychiatric disorder is bipolar disorder.
9. The method of claim 5 , wherein the psychiatric disorder is bipolar disorder.
10. The method of claim 1 , wherein the psychiatric disorder is depression.
11. The method of claim 5 , wherein the psychiatric disorder is depression.
12. The method of claim 1 , wherein the psychiatric disorder is mania.
13. The method of claim 5 , wherein the psychiatric disorder is mania.
14. The method of claim 1 , wherein the psychiatric disorder is anxiety.
15. The method of claim 5 , wherein the psychiatric disorder is anxiety.