Claims for Patent: 8,796,276

Summary for Patent: 8,796,276

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. ##STR00001##
Inventor(s):	Remenar; Julius F. (Framingham, MA), Blumberg; Laura Cook (Lincoln, MA), Zeidan; Tarek A. (Watertown, MA)
Assignee:	Alkermes Pharma Ireland Limited (Dublin, IE)
Application Number:	13/607,066
Patent Claims:	1. 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: ##STR00950## wherein represents a single or double bond; A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl; R.sub.1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.2 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.3 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.4 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; R.sub.11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; D is selected from absent, --O--, --NR.sub.10, --C(R.sub.10)(R.sub.11)-- and --S--, --S(O)--, --S(O).sub.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, R.sub.5 is selected from Table 1; TABLE-US-00012 TABLE 1 ##STR00951## ##STR00952## ##STR00953## ##STR00954## ##STR00955## ##STR00956## ##STR00957## ##STR00958## ##STR00959## ##STR00960## ##STR00961## ##STR00962## ##STR00963## ##STR00964## ##STR00965## ##STR00966## ##STR00967## ##STR00968## ##STR00969## ##STR00970## ##STR00971## ##STR00972## ##STR00973## ##STR00974## ##STR00975## ##STR00976## ##STR00977## ##STR00978## ##STR00979## ##STR00980## ##STR00981## ##STR00982## ##STR00983## ##STR00984## ##STR00985## ##STR00986## ##STR00987## ##STR00988## ##STR00989## ##STR00990## ##STR00991## ##STR00992## ##STR00993## ##STR00994## ##STR00995## ##STR00996## ##STR00997## ##STR00998## ##STR00999## ##STR01000## ##STR01001## ##STR01002## ##STR01003## ##STR01004## ##STR01005## ##STR01006## ##STR01007## ##STR01008## ##STR01009## ##STR01010## ##STR01011## ##STR01012## ##STR01013## ##STR01014## ##STR01015## ##STR01016## ##STR01017## ##STR01018## ##STR01019## ##STR01020## ##STR01021## ##STR01022## ##STR01023## ##STR01024## ##STR01025## ##STR01026## ##STR01027## ##STR01028## ##STR01029## ##STR01030## ##STR01031## ##STR01032## ##STR01033## ##STR01034## ##STR01035## ##STR01036## ##STR01037## ##STR01038## ##STR01039## ##STR01040## ##STR01041## ##STR01042## ##STR01043## ##STR01044## ##STR01045## ##STR01046## ##STR01047## ##STR01048## ##STR01049## ##STR01050## ##STR01051## ##STR01052## ##STR01053## ##STR01054## ##STR01055## ##STR01056## ##STR01057## ##STR01058## ##STR01059## ##STR01060## ##STR01061## ##STR01062## ##STR01063## ##STR01064## ##STR01065## ##STR01066## ##STR01067## ##STR01068## ##STR01069## ##STR01070## ##STR01071## ##STR01072## ##STR01073## ##STR01074## ##STR01075## ##STR01076## ##STR01077## ##STR01078## ##STR01079## ##STR01080## ##STR01081## ##STR01082## ##STR01083## ##STR01084## ##STR01085## ##STR01086## ##STR01087## ##STR01088## ##STR01089## ##STR01090## ##STR01091## ##STR01092## ##STR01093## ##STR01094## ##STR01095## ##STR01096## ##STR01097## ##STR01098## ##STR01099## ##STR01100## ##STR01101## ##STR01102## ##STR01103## ##STR01104## ##STR01105## ##STR01106## ##STR01107## ##STR01108## ##STR01109## ##STR01110## ##STR01111## ##STR01112## ##STR01113## ##STR01114## ##STR01115## ##STR01116## ##STR01117## ##STR01118## ##STR01119## ##STR01120## ##STR01121## ##STR01122## ##STR01123## ##STR01124## ##STR01125## ##STR01126## ##STR01127## ##STR01128## ##STR01129## ##STR01130## ##STR01131## ##STR01132## ##STR01133## ##STR01134## ##STR01135## ##STR01136## ##STR01137## ##STR01138## ##STR01139## ##STR01140## ##STR01141## ##STR01142## ##STR01143## ##STR01144## ##STR01145## ##STR01146## ##STR01147## ##STR01148## ##STR01149## ##STR01150## ##STR01151## ##STR01152## ##STR01153## ##STR01154## ##STR01155## ##STR01156## ##STR01157## ##STR01158## ##STR01159## ##STR01160## ##STR01161## ##STR01162## ##STR01163## ##STR01164## ##STR01165## ##STR01166## ##STR01167## ##STR01168## ##STR01169## ##STR01170## ##STR01171## ##STR01172## ##STR01173## ##STR01174## ##STR01175## ##STR01176## ##STR01177## ##STR01178## ##STR01179## ##STR01180## ##STR01181## ##STR01182## ##STR01183## ##STR01184## ##STR01185## ##STR01186## ##STR01187## ##STR01188## ##STR01189## ##STR01190## ##STR01191## ##STR01192## ##STR01193## ##STR01194## ##STR01195## ##STR01196## ##STR01197## ##STR01198## ##STR01199## ##STR01200## ##STR01201## ##STR01202## ##STR01203## ##STR01204## ##STR01205## ##STR01206## ##STR01207## ##STR01208## ##STR01209## ##STR01210## ##STR01211## ##STR01212## ##STR01213## ##STR01214## ##STR01215## ##STR01216## ##STR01217## ##STR01218## ##STR01219## ##STR01220## ##STR01221## ##STR01222## ##STR01223## ##STR01224## ##STR01225## ##STR01226## ##STR01227## ##STR01228## ##STR01229## ##STR01230## ##STR01231## ##STR01232## ##STR01233## ##STR01234## ##STR01235## ##STR01236## ##STR01237## ##STR01238## ##STR01239## ##STR01240## ##STR01241## ##STR01242## ##STR01243## ##STR01244## ##STR01245## ##STR01246## ##STR01247## ##STR01248## ##STR01249## ##STR01250## ##STR01251## ##STR01252## ##STR01253## ##STR01254## ##STR01255## ##STR01256## ##STR01257## ##STR01258## ##STR01259## ##STR01260## ##STR01261## ##STR01262## ##STR01263## ##STR01264## ##STR01265## ##STR01266## ##STR01267## ##STR01268## ##STR01269## ##STR01270## ##STR01271## ##STR01272## ##STR01273## ##STR01274## ##STR01275## ##STR01276## ##STR01277## ##STR01278## ##STR01279## ##STR01280## ##STR01281## ##STR01282## ##STR01283## ##STR01284## ##STR01285## ##STR01286## ##STR01287## ##STR01288## ##STR01289## ##STR01290## ##STR01291## ##STR01292## ##STR01293## ##STR01294## ##STR01295## ##STR01296## ##STR01297## ##STR01298## ##STR01299## ##STR01300## ##STR01301## ##STR01302## ##STR01303## ##STR01304## ##STR01305## ##STR01306## ##STR01307## ##STR01308## ##STR01309## ##STR01310## ##STR01311## ##STR01312## ##STR01313## ##STR01314## ##STR01315## ##STR01316## ##STR01317## ##STR01318## ##STR01319## ##STR01320## ##STR01321## ##STR01322## ##STR01323## ##STR01324## ##STR01325## ##STR01326## ##STR01327## ##STR01328## ##STR01329## ##STR01330## ##STR01331## ##STR01332## ##STR01333## ##STR01334## ##STR01335## ##STR01336## ##STR01337## ##STR01338## ##STR01339## ##STR01340## ##STR01341## ##STR01342## ##STR01343## ##STR01344## ##STR01345## ##STR01346## ##STR01347## ##STR01348## ##STR01349## ##STR01350## ##STR01351## ##STR01352## ##STR01353## ##STR01354## ##STR01355## ##STR01356## ##STR01357## Y and M are the same or different and each is a monovalent cation; or M and Y together is a divalent cation. 2. 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-US-00013 TABLE A No Structure 1 ##STR01358## 2 ##STR01359## 3 ##STR01360## 4 ##STR01361## 5 ##STR01362## 6 ##STR01363## 7 ##STR01364## 8 ##STR01365## 9 ##STR01366## 10 ##STR01367## 11 ##STR01368## 12 ##STR01369## 13 ##STR01370## 14 ##STR01371## 15 ##STR01372## 16 ##STR01373## 17 ##STR01374## 18 ##STR01375## 19 ##STR01376## 20 ##STR01377## 21 ##STR01378## 22 ##STR01379## 23 ##STR01380## 24 ##STR01381## 25 ##STR01382## 26 ##STR01383## 27 ##STR01384## 28 ##STR01385## 29 ##STR01386## 30 ##STR01387## 31 ##STR01388## 32 ##STR01389## 33 ##STR01390## 34 ##STR01391## 35 ##STR01392## 36 ##STR01393## 37 ##STR01394## 38 ##STR01395## 39 ##STR01396## 40 ##STR01397## 41 ##STR01398## 42 ##STR01399## 43 ##STR01400## 44 ##STR01401## 45 ##STR01402## 46 ##STR01403## 47 ##STR01404## 48 ##STR01405## 49 ##STR01406## 50 ##STR01407## 51 ##STR01408## 52 ##STR01409## 53 ##STR01410## 54 ##STR01411## 55 ##STR01412## 56 ##STR01413## 57 ##STR01414## 58 ##STR01415## 59 ##STR01416## 60 ##STR01417## 61 ##STR01418## 62 ##STR01419## 63 ##STR01420## 64 ##STR01421## 65 ##STR01422## 66 ##STR01423## 67 ##STR01424## 68 ##STR01425## 69 ##STR01426## 70 ##STR01427## 71 ##STR01428## 72 ##STR01429## 73 ##STR01430## 74 ##STR01431## 75 ##STR01432## 76 ##STR01433## 77 ##STR01434## 78 ##STR01435## 79 ##STR01436## 80 ##STR01437## 81 ##STR01438## 82 ##STR01439## 83 ##STR01440## 84 ##STR01441## 85 ##STR01442## 86 ##STR01443## 87 ##STR01444## 88 ##STR01445## 89 ##STR01446## 90 ##STR01447## 91 ##STR01448## 92 ##STR01449## 93 ##STR01450## 94 ##STR01451## 95 ##STR01452## 96 ##STR01453## 97 ##STR01454## 98 ##STR01455## 99 ##STR01456## 100 ##STR01457## 101 ##STR01458## 102 ##STR01459## 103 ##STR01460## 104 ##STR01461## 105 ##STR01462## 106 ##STR01463## 107 ##STR01464## 108 ##STR01465## 109 ##STR01466## 110 ##STR01467## 111 ##STR01468## 112 ##STR01469## 113 ##STR01470## 114 ##STR01471## 115 ##STR01472## 116 ##STR01473## 117 ##STR01474## 118 ##STR01475## TABLE-US-00014 TABLE B No Structure 150 ##STR01476## 151 ##STR01477## 152 ##STR01478## 153 ##STR01479## 154 ##STR01480## 155 ##STR01481## 156 ##STR01482## 157 ##STR01483## 158 ##STR01484## 159 ##STR01485## 160 ##STR01486## 161 ##STR01487## 162 ##STR01488## 163 ##STR01489## 164 ##STR01490## 165 ##STR01491## 166 ##STR01492## 167 ##STR01493## 168 ##STR01494## 169 ##STR01495## 170 ##STR01496## 171 ##STR01497## 172 ##STR01498## 173 ##STR01499## 174 ##STR01500## 175 ##STR01501## 176 ##STR01502## 177 ##STR01503## 178 ##STR01504## 179 ##STR01505## 180 ##STR01506## 181 ##STR01507## 182 ##STR01508## 183 ##STR01509## 184 ##STR01510## 185 ##STR01511## 186 ##STR01512## 187 ##STR01513## 188 ##STR01514## 189 ##STR01515## 190 ##STR01516## 191 ##STR01517## 192 ##STR01518## 193 ##STR01519## 194 ##STR01520## 195 ##STR01521## 196 ##STR01522## 197 ##STR01523## 198 ##STR01524## 199 ##STR01525## 200 ##STR01526## 201 ##STR01527## 202 ##STR01528## 203 ##STR01529## 204 ##STR01530## 205 ##STR01531## 206 ##STR01532## 207 ##STR01533## 208 ##STR01534## 209 ##STR01535## 210 ##STR01536## 211 ##STR01537## 212 ##STR01538## 213 ##STR01539## 214 ##STR01540## 215 ##STR01541## 216 ##STR01542## 217 ##STR01543## 218 ##STR01544## 219 ##STR01545## 220 ##STR01546## 221 ##STR01547## 222 ##STR01548## 223 ##STR01549## 224 ##STR01550## 225 ##STR01551## 226 ##STR01552## 227 ##STR01553## 228 ##STR01554## 229 ##STR01555## 230 ##STR01556## 231 ##STR01557## 232 ##STR01558## 233 ##STR01559## 234 ##STR01560## 235 ##STR01561## 236 ##STR01562## 237 ##STR01563## 238 ##STR01564## 239 ##STR01565## 240 ##STR01566## 241 ##STR01567## 242 ##STR01568## 243 ##STR01569## 244 ##STR01570## 245 ##STR01571## 246 ##STR01572## 247 ##STR01573## 248 ##STR01574## 249 ##STR01575## 250 ##STR01576## 251 ##STR01577## 252 ##STR01578## 253 ##STR01579## 254 ##STR01580## 255 ##STR01581## 256 ##STR01582## 257 ##STR01583## 258 ##STR01584## 259 ##STR01585## 260 ##STR01586## 261 ##STR01587## 262 ##STR01588## 263 ##STR01589## 264 ##STR01590## 265 ##STR01591## 266 ##STR01592## 267 ##STR01593## 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: ##STR01594## wherein represents a single or double bond; A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl; R.sub.1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.2 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.3 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.4 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; R.sub.11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; D is selected from absent, --O--, --NR.sub.10, --C(R.sub.10)(R.sub.11)-- and --S--, --S(O)--, --S(O).sub.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 R.sub.5 is selected from: ##STR01595## wherein R.sub.105, R.sub.106 and R.sub.107 are independently selected from hydrogen, halogen, optionally substituted C.sub.1-C.sub.24 alkyl, optionally substituted C.sub.2-C.sub.24 alkenyl, optionally substituted C.sub.2-C.sub.24 alkynyl, optionally substituted C.sub.3-C.sub.24 cycloalkyl, optionally substituted C.sub.1-C.sub.24 alkoxy, optionally substituted C.sub.1-C.sub.24 alkylamino and optionally substituted C.sub.1-C.sub.24 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. 4. 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: ##STR01596## wherein represents a single or double bond; A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl; R.sub.1 is independently selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.2 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.3 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.4 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; R.sub.11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; D is selected from absent, --O--, --NR.sub.10, --C(R.sub.10)(R.sub.11)-- and --S--, --S(O)--, --S(O).sub.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 R.sub.5 is selected from: ##STR01597## ##STR01598## ##STR01599## wherein, each x and y is independently an integer between 0 and 30, and wherein R.sub.105, R.sub.106 and R.sub.107 are independently selected from hydrogen, halogen, optionally substituted C.sub.1-C.sub.24 alkyl, optionally substituted C.sub.2-C.sub.24 alkenyl, optionally substituted C.sub.2-C.sub.24 alkynyl, optionally substituted C.sub.3-C.sub.24 cycloalkyl, optionally substituted C.sub.1-C.sub.24 alkoxy, optionally substituted C.sub.1-C.sub.24 alkylamino and optionally substituted C.sub.1-C.sub.24 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. 5. 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: ##STR01600## wherein represents a single or double bond; A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl; R.sub.1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.2 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.3 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.4 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; R.sub.11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; D is selected from absent, --O--, --NR.sub.10, --C(R.sub.10)(R.sub.11)-- and --S--, --S(O)--, --S(O).sub.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 R.sub.5 is selected from: ##STR01601## 6. A method of treating schizophrenia, mania, anxiety or bipolar disease by administering a compound selected from Compounds 5-10 or a pharmaceutically acceptable salt thereof to a patient in need thereof: ##STR01602## 7. 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: ##STR01603## wherein represents a single or double bond; A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl; R.sub.1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.2 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.3 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.4 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; R.sub.11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; D is selected from absent, --O--, --NR.sub.10, --C(R.sub.10)(R.sub.11)-- and --S--, --S(O)--, --S(O).sub.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 R.sub.5 is selected from Table 2: TABLE-US-00015 TABLE 2 ##STR01604## ##STR01605## ##STR01606## ##STR01607## ##STR01608## ##STR01609## ##STR01610## ##STR01611## ##STR01612## ##STR01613## ##STR01614## ##STR01615## ##STR01616## ##STR01617## ##STR01618## ##STR01619## ##STR01620## ##STR01621## ##STR01622## ##STR01623## ##STR01624## ##STR01625## ##STR01626## ##STR01627## ##STR01628## ##STR01629## ##STR01630## ##STR01631## ##STR01632## ##STR01633## ##STR01634## ##STR01635## ##STR01636## ##STR01637## ##STR01638## ##STR01639## ##STR01640## ##STR01641## ##STR01642## ##STR01643## ##STR01644## ##STR01645## ##STR01646## ##STR01647## ##STR01648## ##STR01649## ##STR01650## ##STR01651## ##STR01652## ##STR01653## ##STR01654## 8. 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: ##STR01655## wherein represents a single or double bond; A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl; R.sub.1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.2 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.3 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.4 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; R.sub.11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; D is selected from absent, --O--, --NR.sub.10, --C(R.sub.10)(R.sub.11)-- and --S--, --S(O)--, --S(O).sub.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 R.sub.5 is selected from Table 3: TABLE-US-00016 TABLE 3 ##STR01656## ##STR01657## ##STR01658## ##STR01659## ##STR01660## ##STR01661## ##STR01662## ##STR01663## ##STR01664## ##STR01665## ##STR01666## ##STR01667## ##STR01668## ##STR01669## ##STR01670## ##STR01671## ##STR01672## ##STR01673## ##STR01674## ##STR01675## 9. 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: ##STR01676## wherein represents a single or double bond; A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl; R.sub.1 is selected from absent, hydrogen, halogen, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.2 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.3 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.4 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; R.sub.11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; D is selected from absent, --O--, --NR.sub.10, --C(R.sub.10)(R.sub.11)-- and --S--, --S(O)--, --S(O).sub.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 R.sub.5 is selected from Table 4: TABLE-US-00017 TABLE 4 ##STR01677## ##STR01678## ##STR01679## ##STR01680## ##STR01681## ##STR01682## ##STR01683## ##STR01684## ##STR01685## ##STR01686## ##STR01687## ##STR01688## ##STR01689## ##STR01690## ##STR01691## ##STR01692## ##STR01693## ##STR01694## ##STR01695## ##STR01696## ##STR01697## ##STR01698## ##STR01699## ##STR01700## ##STR01701## ##STR01702## ##STR01703## ##STR01704## ##STR01705## ##STR01706## ##STR01707## ##STR01708## ##STR01709## ##STR01710## ##STR01711## ##STR01712## ##STR01713## ##STR01714## ##STR01715## ##STR01716## ##STR01717## ##STR01718## ##STR01719## ##STR01720## 10. 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: ##STR01721## or its geometric isomers, enantiomers, diastereomers, racemates, pharmaceutically acceptable salts and solvates thereof: wherein represents a single or double bond; R.sub.5 is selected from --CH(R.sub.10)--OR.sub.20, --CH(R.sub.10)--OC(O)OR.sub.20, --CH(R.sub.10)--OC(O)R.sub.20, --CH(R.sub.10)--OC(O)NR.sub.20R.sub.21, --(CH(R.sub.10))--OPO.sub.3MY, --(CH(R.sub.10))--OP(O)(OR.sub.20)(OR.sub.21), --[CH(R.sub.10)O].sub.z--R.sub.20, --[CH(R.sub.10)O]--C(O)OR.sub.20, --[CH(R.sub.10)O].sub.z--C(O)R.sub.20, --[CH(R.sub.10)O].sub.z--C(O)NR.sub.20R.sub.21, --[CH(R.sub.10)O]z-OPO.sub.3MY, --[CH(R.sub.10)O].sub.z--P(O).sub.2(OR.sub.20)M and --[CH(R.sub.10)O].sub.z--P(O)(OR.sub.20)(OR.sub.21); wherein z is 1, 2, 3, 4, 5, 6, or 7; each R.sub.20 and R.sub.21 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; R.sub.10 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. 11. A method of treating schizophrenia, mania, anxiety or bipolar disease by administering a compound of formula: ##STR01722## or a pharmaceutically acceptable salt thereof to a patient in need thereof. 12. A method of treating schizophrenia, mania, anxiety or bipolar disease by administering a compound of formula: ##STR01723## or a pharmaceutically acceptable salt thereof to a patient in need thereof. 13. A method of treating schizophrenia, mania, anxiety or bipolar disease by administering a compound of formula: ##STR01724## or a pharmaceutically acceptable salt thereof to a patient in need thereof. 14. 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: ##STR01725## wherein represents a single or double bond; wherein A is selected from absent, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkenyl; R.sub.2 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl. R.sub.3 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.4 is selected from absent, hydrogen, halogen, --OR.sub.10, --SR.sub.10, --N(R.sub.10)(R.sub.11), --S(O)R.sub.10, --S(O).sub.2R.sub.10, optionally substituted aliphatic, optionally substituted aryl or optionally substituted heterocyclyl; R.sub.5 is selected from --CH(R.sub.10)--OR.sub.20, --CH(R.sub.10)--OC(O)OR.sub.20, --CH(R.sub.10)--OC(O)R.sub.20, --CH(R.sub.10)--OC(O)NR.sub.20R.sub.21, --(CH(R.sub.10))--OPO.sub.3MY, --(CH(R.sub.10))--OP(O)(OR.sub.20)(OR.sub.21), --[CH(R.sub.10)O].sub.z--R.sub.20, --[CH(R.sub.10)O].sub.z--C(O)OR.sub.20, --[CH(R.sub.10)O].sub.z--C(O)R.sub.20, --[CH(R.sub.10)O].sub.z--C(O)NR.sub.20R.sub.21, --[CH(R.sub.10)O]z-OPO.sub.3MY, --[CH(R.sub.10)O].sub.z--P(O).sub.2(OR.sub.20)M and --[CH(R.sub.10)O].sub.z--P(O)(OR.sub.20)(OR.sub.21); wherein z is 1, 2, 3, 4, 5, 6, or 7; each R.sub.20 and R.sub.71 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; R.sub.10 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; R.sub.11 is absent, hydrogen, halogen, aliphatic, substituted aliphatic, aryl or substituted aryl; D is selected from absent, --O--, --NR.sub.10, --C(R.sub.10)(R.sub.11)-- and --S--, --S(O)--, --S(O).sub.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 R.sub.1 is selected from: ##STR01726## ##STR01727## wherein R.sub.100 R.sub.101, and R.sub.103 are independently selected from hydrogen, halogen, optionally substituted C.sub.1-C.sub.8 alkyl, optionally substituted C.sub.2-C.sub.8 alkenyl, optionally substituted C.sub.2-C.sub.8 alkynyl, optionally substituted C.sub.3-C.sub.8 cycloalkyl, optionally substituted C.sub.1-C.sub.8 alkoxy, optionally substituted C.sub.1-C.sub.8 alkylamino and optionally substituted C.sub.1-C.sub.8 aryl. 15. The method according to claim 14, wherein R.sub.1 is selected from: ##STR01728##