Pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalines derivatives and [1,4]oxazino[2,3,4-hi]pyrido[4,3-b]indole derivatives
The invention relates to particular substituted heterocycle fused gamma-carbolines of formula I: as described herein, their prodrugs, in free, solid, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT 2A receptor, serotonin transporter (SERT) and/or pathways involving dopamine D2 receptor signaling systems.
1. A compound of Formula I:
wherein:
X is —N(H)— or —N(CH 3 )— and Y is —C(H)(OH)—;
in solid free base or salt form.
2. A compound of Formula I
wherein:
X is —N(H)— or —N(CH 3 )— and Y is —C(H)(OH)—;
in free base or pharmaceutically acceptable salt form, wherein said compound is greater than 70% free of a compound of Formula Q:
wherein
X is —N(H)— or —N(CH 3 )— and Y is —C(═O).
3. The compound according to claim 2 , wherein said compound is greater than 90% free of the compound of Formula Q.
4. The compound according to claim 2 , wherein X is —N(CH 3 )—, in free base or pharmaceutically acceptable salt form.
5. A compound of Formula III:
wherein:
X is —N(CH 3 )— or —N(H)—; and
R 1 is —C(O)—C 1-21 alkyl optionally saturated or unsaturated and optionally substituted with one or more hydroxy or C 1-22 alkoxy groups,
in free base or salt form.
6. The compound according to claim 5 , wherein
R 1 is —C(O)—C 3 alkyl,
in free base or salt form.
7. The compound according to claim 6 , wherein the compound of Formula III is:
in free base or salt form.
8. The compound according to claim 5 , wherein X is —N(CH 3 )—, in free base or salt form.
9. The compound according to claim 5 , wherein said compound is selected from the group consisting of:
in free base or salt form.
10. A pharmaceutical composition comprising a compound of formula I:
wherein:
X is —N(H)— or N(CH 3 )— and Y is —C(H)(OH)—;
in free base or pharmaceutically acceptable salt form,
in admixture with a pharmaceutically acceptable diluent or carrier.
11. The pharmaceutical composition according to claim 10 , wherein said compound is in a pharmaceutically acceptable salt form.
12. The pharmaceutical composition according to claim 11 , wherein the pharmaceutically acceptable salt is selected from a group consisting of toluenesulfonic, fumaric and phosphoric acid addition salts.
13. The pharmaceutical composition according to claim 10 , wherein said compound is:
in free base or pharmaceutically acceptable salt form.
14. The pharmaceutical composition according to claim 13 , wherein said compound is in free base form.
15. The pharmaceutical composition according to claim 10 , wherein the compound of formula I is in free base form.
16. A pharmaceutical composition comprising a compound of Formula II-A:
wherein X is —N(CH 3 )— or —N(H)—, in free base or pharmaceutically acceptable salt form, in admixture with a pharmaceutically acceptable diluent or carrier.
17. The pharmaceutical composition according to claim 16 , wherein X is —N(CH 3 )—, in free base or pharmaceutically acceptable salt form.
18. A pharmaceutical composition comprising a compound of Formula II-B:
wherein X is —N(CH 3 )— or —N(H)—, in free base or pharmaceutically acceptable salt form, in admixture with a pharmaceutically acceptable diluent or carrier.
19. The pharmaceutical composition according to claim 18 , wherein
X is —N(CH 3 )—, in free base or pharmaceutically acceptable salt form.