| 摘要 |
The invention relates to particular substituted heterocycle fused gamma-carbolines, their prodrugs, in free, 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-HT2A receptor, serotonin transporter (SERT) and/or pathways involving dopamine D2 receptor signaling systems. |
| 主权项 |
1. A compound selected from:
a) a compound of Formula Iwherein:
X is —N(H)—, —N(C1-6alkyl)- or —O—; Y is —C(O)—, —O— or —C(H)(OR4)—; R8 is —C(Ra)(Rb)(Rc), —O—C(Ra)(Rb)(Rc) or —N(Rd)(Re); Ra, Rb and Rc are independently H or C1-24alkyl; Rd and Re are independently H or C1-24alkyl; R6 and R7 are independently H or C1-6alkyl; R4 is H or —C(O)—C1-21 alkyl; and W− is a pharmaceutically acceptable anion; b) a compound of Formula II:wherein:
Y is —C(O)—, —O— or —C(H)(OR4)—; R4 is H or —C(O)—C1-21 alkyl; R5 is —C(O)—O—C(Ra)(Rb)(Rc) or —C(R6)(R7)—O—C(O)—R8; R8 is —C(Ra)(Rb)(Rc), —O—C(Ra)(Rb)(Rc) or —N(Rd)(Re); Ra, Rb and Rc are independently H or C1-24alkyl; Rd and Re are independently H or C1-24alkyl; and R6 and R7 are independently H or C1-6alkyl; c) a compound of Formula III:wherein:
X is —N(H)—, —N(C1-4alkyl)- or —O—; R8 is —C(Ra)(Rb)(Rc), —O—C(Ra)(Rb)(Rc) or —N(Rd)(Re); Ra, Rb and Rc are independently H or C1-24alkyl; Rd and Re are independently H or C1-24alkyl; R6 and R7 are independently H or C1-6alkyl; R1 is H or C1-6alkyl (e.g., methyl); R2 is H or OR3 wherein R3 is H, C1-6alkyl (e.g., methyl) or —C(O)—C1-21 alkyl, provided that R1 and R2 are not both H, R1 and R3 are not both H, and when R3 is —C(O)—C1-21alkyl, R1 is C1-6alkyl (e.g., methyl); and W− is a pharmaceutically acceptable anion. d) a compound of Formula IV:wherein:
R5 is —C(O)—O—C(Ra)(Rb)(Rc) or —C(R6)(R7)—O—C(O)—R8; R8 is —C(Ra)(Rb)(Rc), —O—C(Ra)(Rb)(Rc) or —N(Rd)(Re); Ra, Rb and Rc are independently H or C1-24alkyl; Rd and Re are independently H or C1-24alkyl; R6 and R7 are independently H or C1-6alkyl; R1 is H or C1-6alkyl (e.g., methyl); R2 is H or OR3 wherein R3 is H, C1-6alkyl (e.g., methyl) or —C(O)—C1-21 alkyl; provided that R1 and R2 are not both H, R1 and R3 are not both H, and when R3 is —C(O)—C1-21alkyl, R1 is C1-6alkyl (e.g., methyl),in free, salt or prodrug form. |
