Heterocyclic compounds for the treatment of neurological and psychological disorders

A method of treating schizophrenia, mania, bipolar disorder, anxiety or depression by administering a compound selected from Table A or B or the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof to a patient in need thereof:

• TABLE A
• No
• Structure
• 1
• 2
• 3
• 4
• 5
• 6
• 7
• 8
• 9
• 10
• 11
• 12
• 13
• 14
• 15
• 16
• 17
• 18
• 19
• 20
• 21
• 22
• 23
• 24
• 25
• 26
• 27
• 28
• 29
• 30
• 31
• 32
• 33
• 34
• 35
• 36
• 37
• 38
• 39
• 40
• 41
• 42
• 43
• 44
• 45
• 46
• 47
• 48
• 49
• 50
• 51
• 52
• 53
• 54
• 55
• 56
• 57
• 58
• 59
• 60
• 61
• 62
• 63
• 64
• 65
• 66
• 67
• 68
• 69
• 70
• 71
• 72
• 73
• 74
• 75
• 76
• 77
• 78
• 79
• 80
• 81
• 82
• 83
• 84
• 85
• 86
• 87
• 88
• 89
• 90
• 91
• 92
• 93
• 94
• 95
• 96
• 97
• 98
• 99
• 100
• 101
• 102
• 103
• 104
• 105
• 106
• 107
• 108
• 109
• 110
• 111
• 112
• 113
• 114
• 115
• 116
• 117
• 118
• TABLE B
• No
• Structure
• 150
• 151
• 152
• 153
• 154
• 155
• 156
• 157
• 158
• 159
• 160
• 161
• 162
• 163
• 164
• 165
• 166
• 167
• 168
• 169
• 170
• 171
• 172
• 173
• 174
• 175
• 176
• 177
• 178
• 179
• 180
• 181
• 182
• 183
• 184
• 185
• 186
• 187
• 188
• 189
• 190
• 191
• 192
• 193
• 194
• 195
• 196
• 197
• 198
• 199
• 200
• 201
• 202
• 203
• 204
• 205
• 206
• 207
• 208
• 209
• 210
• 211
• 212
• 213
• 214
• 215
• 216
• 217
• 218
• 219
• 220
• 221
• 222
• 223
• 224
• 225
• 226
• 227
• 228
• 229
• 230
• 231
• 232
• 233
• 234
• 235
• 236
• 237
• 238
• 239
• 240
• 241
• 242
• 243
• 244
• 245
• 246
• 247
• 248
• 249
• 250
• 251
• 252
• 253
• 254
• 255
• 256
• 257
• 258
• 259
• 260
• 261
• 262
• 263
• 264
• 265
• 266
• 267

A method of treating schizophrenia, mania, bipolar disorder, anxiety or depression by administering a compound of Formula III or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates to a patient in need thereof:

• wherein represents a single or double bond;
• A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl;
• R1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R2 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R3 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R4 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• R11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• D is selected from absent, —O—, —NR10, —C(R10)(R11)— and —S—, —S(O)—, —S(O)2—, —C(O)—;
• m and q are independently selected from 0, 1, and 2;
• p is 0, 1, 2, 3 or 4;
• r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11;
• and,
• wherein R5 is selected from:
• wherein R105, R106 and R107 are independently selected from hydrogen, halogen, optionally substituted C1-C24 alkyl, optionally substituted C2-C24 alkenyl, optionally substituted C2-C24 alkynyl, optionally substituted C3-C24 cycloalkyl, optionally substituted C1-C24 alkoxy, optionally substituted C1-C24 alkylamino and optionally substituted C1-C24 aryl;
• and,
• Y and M are the same or different and each is a monovalent cation;
• or M and Y together is a divalent cation.

A method of treating schizophrenia, mania, bipolar disorder, anxiety or depression by administering a compound of Formula III or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates to a patient in need thereof:

• wherein represents a single or double bond;
• A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl;
• R1 is independently selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R2 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R3 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R4 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• R11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• D is selected from absent, —O—, —NR10, —C(R10)(R11)— and —S—, —S(O)—, —S(O)2—, —C(O)—;
• m and q are independently selected from 0, 1, and 2;
• p is 0, 1, 2, 3 or 4;
• r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11;
• and,
• wherein R5 is selected from:
• wherein, each x and y is independently an integer between 0 and 30, and
• wherein R105, R106 and R107 are independently selected from hydrogen, halogen, optionally substituted C1-C24 alkyl, optionally substituted C2-C24 alkenyl, optionally substituted C2-C24 alkynyl, optionally substituted C3-C24 cycloalkyl, optionally substituted C1-C24 alkoxy, optionally substituted C1-C24 alkylamino and optionally substituted C1-C24 aryl;
• and,
• Y and M are the same or different and each is a monovalent cation;
• or M and Y together is a divalent cation.

A method of treating schizophrenia, mania, bipolar disorder, anxiety or depression by administering a compound of Formula III or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates to a patient in need thereof:

• wherein represents a single or double bond;
• A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl;
• R1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R2 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R3 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R4 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• R11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• D is selected from absent, —O—, —NR10, —C(R10)(R11)— and —S—, —S(O)—, —S(O)2—, —C(O)—;
• m and q are independently selected from 0, 1, and 2;
• p is 0, 1, 2, 3 or 4;
• r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11;
• and,
• wherein R5 is selected from:

A method of treating schizophrenia, mania, bipolar disorder, anxiety or depression by administering a compound of Formula III or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates to a patient in need thereof:

• wherein represents a single or double bond;
• A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl;
• R1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R2 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R3 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R4 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• R11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• D is selected from absent, —O—, —NR10, —C(R10)(R11)— and —S—, —S(O)—, —S(O)2—, —C(O)—;
• m and q are independently selected from 0, 1, and 2;
• p is 0, 1, 2, 3 or 4;
• r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11;
• and,
• wherein R5 is selected from Table 2:
• TABLE 2

A method of treating schizophrenia, mania, bipolar disorder, anxiety or depression by administering a compound of Formula III or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates to a patient in need thereof:

• wherein represents a single or double bond;
• A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl;
• R1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R2 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R3 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R4 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• R11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• D is selected from absent, —O—, —NR10, —C(R10)(R11)— and —S—, —S(O)—, —S(O)2—, —C(O)—;
• m and q are independently selected from 0, 1, and 2;
• p is 0, 1, 2, 3 or 4;
• r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11;
• and,
• wherein R5 is selected from Table 3:
• TABLE 3

A method of treating schizophrenia, mania, bipolar disorder, anxiety or depression by administering a compound of Formula III or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates to a patient in need thereof:

• wherein represents a single or double bond;
• A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl;
• R1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R2 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R3 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R4 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• R11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• D is selected from absent, —O—, —NR10, —C(R10)(R11)— and —S—, —S(O)—, —S(O)2—, —C(O)—;
• m and q are independently selected from 0, 1, and 2;
• p is 0, 1, 2, 3 or 4;
• r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11;
• and,
• wherein R5 is selected from Table 4:
• TABLE 4

A method of treating schizophrenia, mania, anxiety or bipolar disease by administering a compound of Formula V or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates to a patient in need thereof:

• or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof:
• wherein represents a single or double bond;
• R5 is selected from —CH(R10)—OR20, —CH(R10)—OC(O)OR20, —CH(R10)—OC(O)R20, —CH(R10)—OC(O)NR20R21, —(CH(R10))—OPO3MY, —(CH(R10))—OP(O)(OR20)(OR21), —[CH(R10)O]z—R20, —[CH(R10)O]—C(O)OR20, —[CH(R10)O]z—C(O)R20, —[CH(R10)O]z—C(O)NR20R21, —[CH(R10)O]z-OPO3MY, —[CH(R10)O]z—P(O)2(OR20)M and —[CH(R10)O]z—P(O)(OR20)(OR21);
• wherein z is 1, 2, 3, 4, 5, 6, or 7;
• each R20 and R21 is independently selected from hydrogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• Y and M are the same or different and each is a monovalent cation;
• or M and Y together is a divalent cation;
• R10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• and,
• w is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11.

A method of treating schizophrenia, mania, bipolar disorder, anxiety or depression by administering a compound of Formula III or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts or solvates to a patient in need thereof:

• wherein represents a single or double bond;
• wherein A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl;
• R2 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl.
• R3 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R4 is selected from absent, hydrogen, halogen, —OR10, —SR10, —N(R10)(R11), —S(O)R10, —S(O)2R10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl;
• R5 is selected from —CH(R10)—OR20, —CH(R10)—OC(O)OR20, —CH(R10)—OC(O)R20, —CH(R10)—OC(O)NR20R21, —(CH(R10))—OPO3MY, —(CH(R10))—OP(O)(OR20)(OR21), —[CH(R10)O]z—R20, —[CH(R10)O]z—C(O)OR20, —[CH(R10)O]z—C(O)R20, —[CH(R10)O]z—C(O)NR20R21, —[CH(R10)O]z-OPO3MY, —[CH(R10)O]z—P(O)2(OR20)M and —[CH(R10)O]z—P(O)(OR20)(OR21);
• wherein z is 1, 2, 3, 4, 5, 6, or 7;
• each R20 and R71 is independently selected from hydrogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• Y and M are the same or different and each is a monovalent cation;
• or M and Y together is a divalent cation;
• R10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• R11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl;
• D is selected from absent, —O—, —NR10, —C(R10)(R11)— and —S—, —S(O)—, —S(O)2—, —C(O)—;
• m and q are independently selected from 0, 1, and 2;
• p is 0, 1, 2, 3 or 4;
• r is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11;
• and,
• wherein R1 is selected from:
• wherein R100 R101, and R103 are independently selected from hydrogen, halogen, optionally substituted C1-C8 alkyl, optionally substituted C2-C8 alkenyl, optionally substituted C2-C8 alkynyl, optionally substituted C3-C8 cycloalkyl, optionally substituted C1-C8 alkoxy, optionally substituted C1-C8 alkylamino and optionally substituted C1-C8 aryl.