Claims for Patent: 8,431,576

Summary for Patent: 8,431,576

Title:	Heterocyclic compounds for the treatment of neurological and psychological disorders
Abstract:	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.
Inventor(s):	Julius F. Remenar, Laura Cook Blumberg, Tarek A. Zeidan
Assignee:	Alkermes Pharma Ireland Ltd
Application Number:	US12/823,007
Patent Claims:	1. A compound having the Formula: wherein represents a single or double bond; or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: wherein 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 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; 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; each R6 is independently selected from hydrogen, halogen, OR10, SR10, NR10R11, aliphatic, substituted aliphatic, aromatic, substituted aromatic, wherein each R10 and R11 are independently hydrogen, halogen, aliphatic, substituted aliphatic aryl or substituted aryl; or alternatively two adjacent R6 groups form a second ring; and t and s are independently selected from 0, 1, and 2. 2. A compound of claim 1 having the Formula: 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]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 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; R11 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. 3. A compound having the Formula: wherein represents a single or double bond; or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: wherein, A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, —S—, —O—, —S(O)—, —S(O)2—, —S[C(R10)(R11)]u—, —S(O)[C(R10)(R11)]u—, —S(O)2[C(R10)(R11)]u—, —O[C(R10)(R11)]u—, —N(R10)—, —N(R10)—[C(R10)(R11)]u—, —[C(R10)(R11)]u; wherein each u is independently 1, 2, 3, 4, 5, 6 or 7; wherein each R10 and R11 is independently absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; Each R1, R2, R3 and R4 is independently 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 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; R11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; each G3 and G4 is independently selected from —N—, and —C(R10)—[C(R10)(R11)]a—, wherein a is 0, 1 or 2; 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, X2 is —S— or —O—. 4. A compound of claim 1, wherein R5 is selected from Table 1, 2, 3 or 4; TABLE 1 TABLE 2 TABLE 3 TABLE 4 5. A compound having the Formula: or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: wherein R5 is selected from Table 1. 6. A compound having the Formula: or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: wherein R5 is selected from Table 1. 7. A compound selected from Table A, B, C, D or E and the geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates 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 TABLE C No. Structure 300 301 302 303 304 305 306 307 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 TABLE D No. Structure 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 430 431 432 433 434 435 436 437 TABLE E No. Structure 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540