TW200530188A - Novel compounds - Google Patents

Abstract

This invention provides one or more chemical entities selected from a compound of formula (I), and a pharmaceutically acceptable salt and solvate thereof. The compound of formula (I) and a pharmacetically acceptable salt or solvate thereof are useful in therapy, in particular an antipsychotic agents.

Description

200530188 IX. Description of the invention: [Technical field to which the invention belongs] # This invention relates to a novel compound called (3H xymethyl 4-yl) _ = fluorenyl] each methoxy_3_methyl_2,3,4, 5_tetrahydro_benzobenzidine, and pharmaceutically acceptable compounds, pharmaceutical compositions containing the compounds, and their use in therapy, especially as antipsychotic agents. 10 15 "See where we find a novel phenylcontinyl compound, and its medically acceptable salts and solvates', which are particularly useful as antipsychotic agents. The compound of formula (1) of this novel, and Its pharmaceutically acceptable salts and solvents 'have a high affinity for the desired receptor, show good%' in the living body, and have good drug metabolism and pharmacokinetic (DMPK) properties. [Previous Technology] 7 < 4- (3-Fluoro-4-methyl-benzyl) _benzenesulfonyl group> 8-methoxy-3_fluorenyl group 2'3,4,5-tetrahydrobenzene nitrogen free base can be borrowed It is prepared by the following method, or the method disclosed in WO 03/99786, which is incorporated herein by reference. [Summary of the Invention] ^ Therefore, in the first aspect of the present invention, a group selected from 7- [4- (3- ^ yl-4-methyl_benzylbenzenesulfonyl) _8_methoxy_3_methyl_2,3,4,5_tetrabenzidine and its pharmaceutically acceptable One or more chemicals of salts and solvates. L: \ menu \ Pending-93 \ 93544. Doc 200530188 7 [4 (3, fluoro 4-methyl_benzyl) -benzenesulfonyl] -8- The structure of methoxyfluorenyl-2,3,4,5-tetrahydro_1IM ⑴ compound shown by the formula:

N—Me (I) as used herein, the term, compound ,,,,,, compound of formula (I), or, or the present compound, means 7- [4- (3-fluorofluorenyl) -Benzyl) -benzylsulfonyl] -8- # monomethyl-2,3,4,5-tetrahydro-111-3-phenylazepine (free test), and soy medicine 10 15 acceptable Salt members and solvates. ', As used herein, the term, solvate, means a complex of different stoichiometry formed by a solute (in the present invention, a substance or a salt thereof) and a solvent. Such solvents for this purpose do not interfere with the biological activity of the solute. Appropriate examples include water, methanol, ethanol, and acetic acid. For example, the solvents used, ',, 7' and the resulting solvates can also be referred to as hydrates. of. Wei must be acceptable for peony, including the example r //, it is obvious to the artist, and acid, hydrogen ^ ... ff form acid addition salts, such as, for example, hydrogen chloride. Ding's oxalic acid or osmic acid; formed with organic acids, such as 'a s acid' phenethyl _ acetic acid, butyl acetate, lactic acid, citric acid, tartaric acid, benzoic acid, benzoic acid , Dimethyl oxalic acid or naphthoic acid. Salts of the compound of formula 只, only 1 d. Lice carbuncle salt, maleic acid salt, terephthalate or methyl L: \ menu \ Pending-93 \ 93544.doc 20 200530188 y Salts, or pharmaceutically acceptable solvates thereof. Other non-physiologically acceptable salts, such as oxalate, can be used, for example, in the isolation of compounds of formula (I) 'and are included in the scope of the present invention. The scope of the invention includes salts, solvates and hydrates of compounds of formula (I). 5 10 15 20 The compound of formula (I) can form acid addition salts with one or more equivalents of an acid. The invention includes in its scope all its possible stoichiometric and non-stoichiometric forms. In another aspect of the present invention, there is provided a salt selected from the group consisting of 7- [4Xinghongfluoro_4_methyl-benzyl) -benzenesulfonylmethoxy-3_methylbenzylazine and a solvate One or more chemicals. In another aspect of the present invention, there is provided a member selected from the group consisting of 7- [4_ (3_fluoro_4_: yl-benzyl) -benzenesulfonyl] -8-methoxy_3_methylbenzyl One or more chemicals of p-toluenesulfonate and its solvate. Depending on the solvent when p-toluene salt is removed from the towel, p-toluate is obtained as a solvent, and this compound also forms an aspect of the present invention. The solvate may be a pharmaceutically acceptable solvate. Suitable solvates include hydrates' such as monohydrates and trihydrate solvates. =, P-Toluene salts are obtained as anhydrate. The anhydrous substance can be less than 2% water, for example, less than 1% water. μ 2-a fortune, providing a chemical or solvent selected from the group consisting of mono-toluate toluate salts and acceptable solvates. In two other perspectives, one or more chemicals are essentially additional salts, additional solvates, or free bases of a solvate. ° Do not or other impurities L: \ menu \ Pending-93 \ 93544.doc 200530188 is basically free of 7- [4- (3-fluoro-4-methyl-benzyl) -benzoxanthenyl] 3-Amino-2,3,4,5-tetrahydro-1 ^ 3-benzazepine, or other impurities, other solvates or free test ", meaning to contain less than 1Q% of 7- [4- (3-Fluoro-4-methyl-benzyl) -benzoxanthenyl] _8-methoxy-3-methyl-2,3,4,5-tetrahydro-111-3-phenyl nitrogen Examination of other salts, solvates, or free impurities, such as: less than 5%, such as less than 2%. The term "other, other impurities" includes not 7- [4- (3-fluoro group 4-Methyl-benzyl > Benzylfluorenyl] -8-methoxy-3-fluorenyl_2,3,4,5-tetrahydro-111-3-phenylazepine 0 10-P-ammonium sulfonate and its pharmaceutically acceptable solvate can each be obtained in non-crystalline, or crystalline, or otherwise homogeneous, multiple forms. Such different forms of salts and solvates are intended to be included in the scope of the present invention Therefore, in another aspect of the present invention, 15-p-toluenesulfonic acid hydrate of a compound of formula (I) is provided, for example: p-toluenesulfonate monohydrate When the compound of formula (I) is prepared, in addition to the fluorene group, the precursor of the compound of formula (I) may have an appropriate atom on the nitrogen atom of the benzene nitrogen ring. (For example: the third-butoxycarbonyl group [BOC]). Such a protecting group is used, for example, when it is easier to introduce a methyl substituent in a synthetic route. In another aspect of the present invention, In one aspect, a general method (A) for preparing a compound of formula (I) is provided, which method comprises: coupling a compound of formula (II): L: \ menu \ Pending-93 \ 93544.doc 200530188

Compounds with formula (III): 5 10 15 20

(ΠΙ) is in a suitable solvent, such as: tetrahydrofuran (THF), such as: zinc chloride (znC1) or brominated ZnBr), R is a methyl group or a hydrazone group, and W is a leaving group , Such as: chloro, phenyl, and trimethylmethanoate, in the presence of _ media, such as 'id palladium [PdO ^ M]' as the case may be under elevated temperature, such as: 6 (rc 1 after ^ this method ( A): It is also recommended to remove any protective groups; • if appropriate, convert the group on the nitrogen atom of the phenyl nitrogen ring, and / or hydrogen to form a fluorenyl group; or to form a pharmaceutically acceptable salt thereof or Examples of the above general method are: W is Br ′ and γ is ZnCl, which can be conveniently performed in an inert solvent, such as tetrahydrofuran in the presence of a (triphenylphosphine) palladium catalyst in For example: at a temperature of 60 ° C. The present invention also provides a general method (B) for preparing a compound of formula (I), which method comprises: L: \ menu \ Pending-93 \ 93544.doc -9- 200530188 coupling formula ( IV) Compound:

5 Compounds with formula (V):

Wherein L is a leaving group, such as, 10 15 aryloxy group, r is a loading group, soil /, soil, bromo group, C1-6 alkoxy group such as, or such as a qi group, M is a metal, m's method (B): • remove any protective groups; • form its pharmaceutically acceptable salt or solvate. This general method (B) can be conveniently mixed at a temperature of -78 ° C to room temperature in a suitable solvent such as four rat squeaking or shouting for 10 minutes to 18 hours. For example, the removal of certain rule protecting groups of trifluoroacetamidine can also be performed simultaneously in this method. Compounds of formula (III) can be prepared by combining compounds of formula (VI):

(VI)

MeO L: \ menu \ Pending-93 \ 93544.doc -10- 20 200530188 and 4_ molybdenite stilbene chloride, for example: indium (III) trifluoromethane, tin (II) trifluoride ), Chlorinated surface (111) or indium chloride or its mixture in the presence of Lewis acid and trifluoromethanesulfonic acid, such as: trifluoroacetic acid, and for example: dichloromethane Instead, a suitable solvent is prepared in a suitable solvent. ~ Compounds of formula (III) can be prepared according to known methods and / or are commercially available. '10 15 20 The compound of formula (IV) can be prepared by known methods, for example, the use of chlorosulfonic acid can be chlorosulfonated in the aromatic ring of benzene nitrogen. If desired, conversion to sulfonyl fluoride can be achieved by reaction with potassium fluoride in acetonitrile at room temperature. Suitable examples of the R group are fluorenyl or a protecting group such as trifluoroethenyl. Compounds of formula (III) can be prepared by combining compounds of formula (VI):

(VI) where L is a bromo group, for example, treated with n-butyllithium at -78 ° C, such as a suitable solvent for tetrahydrofuran. Compounds of formula (VI) can be prepared using methods described in the literature, for example: using the routes described in European patent EP285287. Compounds of formula (VII) can be prepared from 2-fluoro-4-molyltoluene, which is commercially available. Metallization is performed in an appropriate solvent such as tetrahydrofuran at -78 ° C, treated with n-butyllithium, or by the Grignard reagent corresponding to the formation of magnesium filings, and continued to add To 4-bromobenzaldehyde, the corresponding diphenylmethanol is produced. This can then be converted into a compound of formula (VII), where L is Br, and L: \ menu \ Pending-93 \ 93544.doc -11- 200530188 by inert solvents such as chloroform, oQc to room temperature, Treated with triethyl Shixuan and trifluoromethane. The conversion of R groups into methyl groups is generally when a compound of formula (vm) is used as a precursor of a compound of formula ⑴: 5

^ R is not a methyl group, or it is easier to introduce f 10 15 C at the end of the synthesis sequence to two: eg: R is converted from the third -butoxycarbonyl group (B0C) group to 4 ethanol or In the case of smoldering, at room temperature, BOC was used to protect compounds by nitrogen chloride. The conversion from hydrogen to methyl & the conversion of triethylfluorinated borohydride is also carried out in the same manner as in the present invention, or in the presence of m, the name is s NH, 4 (Conditions under TC1 [potassium carbonate in dimethylphosphonium amine (DM) compound. Treatment of radix methyl with a suitable methyl compound such as Emei formazan—one viewpoint is to provide a method for preparing 7 3_fluoro group-4 methyl group (methyl-benzyl group), the method of fluorenyl 222 includes: 7-fluoro-nitrogen and anhydrous __methylcarbamoyl-2, 3,4,5_tetrahydro. 3_ deaf acid in a suitable dissolved gas for a long time, for example in ethyl acetate 'tetrahydrofuran or dark field ^, for example: 6 (TC as the case may be elevated temperature. Ί2- L: \ menu \ Pending-93 \ 93544.doc 20 200530188 7_ [4- (3-Fluoro_4_methyl-benzyl) _benzenesulfonyl] -8-methoxymonomethyl-2, The solvates of 3,4,5-tetrahydro_111-3-phenylazepine salts can be used in a conventional manner, starting from 7_ [4_ (3_fluoroyl-4-methyl-benzyl > benzenesulfonyl) ] _8_methoxy_3_methyl-2,3,4,5-tetrahydro-111-3-phenylazepine salt solution. For example: p-toluenesulfonate monohydrate, 7_ (4- (3-Fluoro ^^ methyl_benzyl ) _Benzenesulfonyl] -8-methoxy-3-methyl-2,3,4,5-tetrahydro-111-3-phenylazepine and p-methanesulfonic acid monohydrate, for example It is prepared by reacting ethyl acetate, methanol, tetrahydrofuran or water in a suitable solvent at room temperature or elevated temperature (for example, up to the boiling point of the solvent used) φ. As used herein, the term "7_ [4_ (3-fluoro 4-Methenyl-benzyl) -benzenesulfonyl) -8-methoxy-3-fluorenyl-2,3,4,5-tetrahydro_111_3_benzoazepine and its pharmaceutically acceptable salts And solvate, which is intended to mean 7_ [4_ (3_fluoro_4_fluorenyl-benzyl) -benzene% fluorenyl> 8-fluorenyloxy-3.methyl-2,3,4,5 -Tetramethyl-111-3_benzidine, or an independent pharmaceutically acceptable salt, or a pharmaceutically acceptable solvate, or 7- [4- (3-^-4-methyl-benzyl) _benzenesulfonate [Methenyl] _8_methoxy_3-Methenyl- ^ 孓 tetra, orphan 3-phenylazepine is a mixture of one or more pharmaceutically acceptable salts and one or more pharmaceutically acceptable solvates. In another aspect of the present invention, hydrazone [4- (3_fluoro group_4_methyl_fluorenyloxy_3_methyl_2,3,4,5-tetraazafluorene, each benzene nitrogen: anhydrous ·· 曱 Oxidite scutellaria double salt is characterized in that it provides roughly as XRPD spectrum shown in Figure 1.-In another aspect of the present invention, 7_ [4_ (3_Gas_cardiomethyl_fluorenylbenzoyl]] | fluorenoxy1fluorenyl_2,3, 4,5_tetrahydro] orthobenzyl nitrogen L: \ menu \ Pending-93 \ 93544.doc -13- 200530188 Called an anhydrous pair, its ship lies in: It provides the XRPD spectrum of the signals in the field. ^ Another perspective of the present invention provides 7_ [4_ (3_fluoro group and its radicals) · benzyl H · methoxyl m_2,3, diH_ l p-f-benzene hetero fresh hydrate ' The idea is that it provides the XRPD spectrum shown in Figure 4. 10 15 20 In another aspect of the present invention, 7_ [4_ (Hongfluoro_4_fluorenyl-benzyl) -benzenesulfonyl] -8-methoxy-3-fluorenyl_2,3 is provided. , 4,5_tetrahydro-111_3_benzene1 # p-toluenebenzenesulfonate monohydrate is characterized in that it provides an XRPD spectrum roughly as the signals listed in Table 2. 7- [4- (3-Fluoro-4-methyl-benzyl) _benzenesulfonyl] -8-methoxy_3_fluorenyl-2,3,4,5-tetrafluorene-111-3 -Benzazepine and its pharmaceutically acceptable salts and solvates' have a strong affinity for dopamine receptors, especially D3 and D2 receptors, and are used to treat those who require such receptors Regulated disease states such as: psychiatric symptoms. Compounds of formula (I) and their pharmaceutically acceptable salts and solvates have been found to have greater affinity for dopamine D3 than D2 receptors. The therapeutic effect of currently available antipsychotic agents (neuroleptics) is generally believed to be exerted by blocking the D2 receptor; however, this mechanism is also considered to be relevant to many antischizophrenic agents You don't want the cone OD path side effects (eps) to be responsible. Unwilling to be bound by theory, it is suggested that blocking of the dopamine D3 receptor increases beneficial antipsychotic activity without significant eps (see, eg, Sokoloff et al., Nature, 1990; 347, 146-151; and Schwarz et al. Human 'Clinical Neuropharmacology, Volume 16, No. 4, 295-314, 1993). L: \ menu \ Pending-93 \ 93544.doc -14- 200530188 Compounds of formula (I) and their pharmaceutically acceptable salts and solvates have been found to have serotonin 5-HT2C, 5-HT2A and 5-HT6 receptors. Affinity. These properties can increase antipsychotic activity (eg, improvement in cognitive dysfunction), reduce eps activity, and / or anxiolytic / depressant activity. These can include, but are not limited to: reduction of cognitive symptoms blocked via 5-HT6 receptors (see, eg, Reavill, C. and Rogers, DC., 2001, Investigational Drugs 2, 104-109), and reduction of anxiety ( See for example: Kennett et al. 10 15 20

Neuropharmacology 1997, April-May; 36 (4-5): 609-20), anti-eps protection (Reavill Nets' Brit · J · Pharmacol "1999; 126: 572-574) and via Antidepressant activity of 5-HT2C receptor block (Bristow et al., Neuropharmacology 39: 2000; 1222-1236) 〇7- [4- (3-Fluoro-4-amidino-benzyl) _benzenesulfonyl ] _8_Methoxy_3_fluorenyl-2,3,4,5-tetrahydroiso-3-phenylazepine & its pharmaceutically acceptable salts and solvates' may also show other than those mentioned above Receptor affinity, resulting in beneficial antipsychotic activity. 7 [4 (3 ^ 4-Amidino-benzyl > benzylfluorenyl] ethoxyfluorenyl-2,3,4,5-tetrakis Hydrogen-threat-benzidine and its pharmaceutically acceptable dragons and solvates are used to treat mental disorders. In another aspect, the present invention provides

”Base brewing group] -8. Methoxy I methyl cut, hydrogen hydride, U pinyin = Therapeutic acceptable salts and solvates-or multiple chemical Toxy-3-fluorenyl · 2,3 , 4,5-tetrahydro-1H-3-benzene L: \ menu \ Pending-93 \ 93544.doc -15- 200530188-or multiple chemistries of pharmaceutically acceptable salts and solvates Mouth is used to treat symptoms that require the regulation of dopamine D3 receptors. In the viewpoint of Hu 2 22! 1, the present invention provides a group selected from 7_ [4 · (3 遗 基 冰 曱 i 胡 广 and 醯 基] · 8_methoxy | Methyl-2,3,4,5, hydrogen-age benzene mouth, one or more chemical mouths of Shangle acceptable salts and solvates, are used to treat mental disorders. In point A, The present invention provides a plurality of chemicals, pharmaceuticals, or chemicals selected from 7 · [4 · (3 · fluoro group_4 · 基 10 15 20), or multiple pharmaceutically acceptable salts and solvates for use in the manufacture of treatments. Base-sections that modulate the symptoms of the dopamine D3 receptor The present invention provides a group selected from the group consisting of 7 · [4 · (3 · fluorofluorobenzyl ^ = yl) each methoxy-3_methyl-2,3,4,5 , The use of hydrogen-de-benzene Diler accepts one or more of the salts and solvates of chemicals, "is used to manufacture the treatment of mental disorders Medicines. Amine is a wide variety, and the present invention provides a treatment that requires the regulation of dopamine, ... methylnaphthylhydrogen] H · 3 · benzidine, and its pharmaceutically acceptable salt cheek and / One or more chemicals of cereals. The method is in the point 'The present invention provides a therapeutically effective amount of mammals for the treatment of mental disorders of Dioscorea selected from the group consisting of -2: m methyldifluorenyl) _benzene continued Fluorenyl] _8_methoxy-3-methyl '' '-tetra-lazepine, and its pharmaceutically acceptable salts and solvated L: \ menu \ Pending-93 \ 93544. Doc -16- 200530188 In the context of the present invention, the terms describing the indications used herein are classified in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition by the American Psychiatric Association (DSM-IV) And / or the International Classification of Diseases, 10th Edition (ICD-10). The various sub-categories of disorders mentioned herein are considered part of the invention. The numbers in the scratches after the following diseases mean Classification code in DSM-IV. In the context of the present invention, Terminology, mental disorders, including: Schizophrenia 'includes subtypes of paranoid (295.30), schizophrenic (295.10), nervous schizophrenic (295.20), undifferentiated (295.90) And 15 20 residual type (295.60); schizophrenic forms of disorders (295.40); emotional schizophrenia (295.70), including sub-types of bipolar and depression; delusional disorders (297.1), including sub-types of pornography Crazy, exaggerated, jealous, persecuted, physical, mixed, and unspecified; simple mental disorders (298 · 8); shared mental disorders (297 · 3); due to general medical conditions Sub-types of 'psychological disorder' include delusions and hallucinations; material triggering = 5 weeks of mental disorder 'include sub-types of delusional ㈣ 川 and hallucinations 82)' and no other specific mental disorders (298.9) . US J-base phenyl phenyl amidinyl group] each of the oxyhydrogenated stilbene tetrakis stilbene benzophenone, and its pharmaceutically acceptable salts and solvates, can also be used to treat the following disorders: = major depression symptoms, manic Mania, mixed symptoms, and τ 'positive' multiple disorders include major depression disorders, light business disorders (30.4), L: \ menu \ Pending-93 \ 93544.doc -17- 200530188 No specific depression Imbalance (311); Bipolar disorders include bipolar disorders, bipolar II disorders (recurrent major worries with hypomania # symptoms), psychiatric disorders (muscle η), and specific bipolar disorders (298 8〇); Other mood disorders include mood disorders due to general medical conditions (298 83), ^ Including subtypes with depression characteristics, seemingly major symptoms of depression, mania characteristics and mixed characteristics; Disorders (including sub-categories of financial anxiety signs, manic features, and mixed features); and unspecified mood disorders (296.90); " Anxiety disorders include social anxiety disorders, panic attacks, wilderness panic disorder, panic disorder Wilderness panic disorder without a history of panic disorder (300.22), specificity Phobia (300 · 29), including subtypes of animal type, natural ring type, blood injection injury type, situational type, and other types; social panic disorder (300.23), delusional obsessive-compulsive disorder (30.3) , Post-traumatic stress disorder (309.81), acute stress disorder (308.3), general anxiety disorder (3000), anxiety disorder due to general medical conditions (293.84), substance-induced anxiety disorder, and no other specific anxiety Disorders (300.00); Substance-related disorders include substance use disorders, such as: substance dependence, substance aspiration, and substance abuse; substance-induced disorders such as substance poisoning, substance withdrawal, substance-induced mental disorder, and substance-induced persistent dementia , Material-induced persistent amnesia, material-induced mental disorders, material-induced mood disorders, material-induced anxiety disorders, material-induced sexual dysfunction, material-induced sleep disorders, and persistent sensory disorders of psychedelic drugs (psychedelic) Drug hallucinations); alcohol-related disorders, such as: alcohol dependence (3309), alcohol abuse (305.00), alcoholism (303.00), alcohol withdrawal (291.81), L: \ menu \ Pending-93 \ 93544.doc • 18- 200530188 Alcoholism mental error "L, Alcohol withdrawal, insanity, Alcohol-induced persistent dementia, Alcohol-induced persistent amnesia, Alcohol-induced Mental disorders, alcohol-induced mood disorders, alcohol-induced anxiety disorders, alcohol-induced sexual dysfunction, alcohol-induced sleep disorders and unspecific alcohol-induced disorders (291.9), amphetamine (or amphetamine-like) disorders, such as : Female amphetamine dependence (304.40), amphetamine abuse (305.70), amphetamine poisoning (292.89), amphetamine withdrawal (292 · 0), insanity caused by amphetamine poisoning, mental disorders caused by amphetamine, and amphetamine-induced Mood disorders, amphetamine-induced anxiety disorders, amphetamine-induced sexual dysfunction, amphetamine-induced sleep disorders, and non-specific amphetamine-related disorders (292 · 9); caffeine-related disorders, such as caffeine poisoning (305.90 ), Anxiety disorders caused by caffeine, sleep disorders caused by caffeine, and non-specific caffeine phase Disorders (292.9); cannabis-related disorders, such as · cannabis dependence (304.30), cannabis abuse (305.20), cannabis poisoning (292.89), mental disorders caused by cannabis poisoning, cannabis-induced mood disorders, cannabis-induced anxiety disorders, and Not specific cannabis-related disorders (292.9); colucoline-related disorders, such as: cocaine dependence (304.20), cocaine abuse (305.60), cocaine poisoning (292.89), cocaine withdrawal (292.0), insanity of coca test poisoning, mental disorders of coca test poisoning, mood disorders caused by coca test, anxiety disorders caused by coca base, sexual dysfunction caused by coca base, cocaine-induced Sleep disorders and non-specific cocaine-related disorders (292.9); psychedelic-related disorders, such as: psychedelic drug dependence (304.50), psychedelic drug abuse (305.30), psychedelic drug poisoning (292.89), Persistence of sensory disorders of psychedelic drugs (psychedelic reproduction of psychedelic drugs) (292.89), L of psychedelic drugs: \ menu \ Pending-93 \ 93544.doc -19- 200530188 Mood disorder, psychedelic rate index 2 = arsenic disorder, psychedelic drug index The Q & A of Ϊ takes into account the imbalance of drug drugs related to other specific hallucinogens, such as: drug dependence (304.6 ^ ^ # (292.89) ^ 10 15 20 ^ intoxication, intoxication, insanity, Persistent therapy for inhaling drug bows, mental disorders caused by pleasure, mood disorders caused by inhaling drugs, anxiety disorders caused by inhaling music, and non-specific inhaling drug-related disorders (292 · 9) , Nicotine-related disorders, such as: Nicotine dependence ⑽]), Nicotine withdrawal (292 takes the non-specific nicotine-related disorders (292 · 9); Hong Pian-related disorders, such as: Opium dependence (304.00), Abuse of quail tablets (305.50), quail tablets (292.89), retreat of Hong tablets (292 〇), mental ill manners of heart towel poison, mental disorders caused by Hong tablets, mood disorders caused by cymbals, sexual functions caused by opium Disorders, opiate-induced sleep disorders and non-specific opiate-related disorders (292.9); phencydidine (or phencyclidine-like) -related disorders such as: phencyclidine dependence (304) 60), phencyclidine abuse (305.90), phencyclidine poisoning (292.89), phencyclidine Insanity of poisoning, mental disorders caused by phencyclidine, mood disorders caused by phencyclidine, anxiety disorders caused by phencyclidine and no particular phencyclidine-related disorders (292.9); Disturbances related to sedatives, sleeping pills, or anxiolytics, such as: tranquilizers, sleeping pills, or anxiolytic dependence (3041), abuse of sedatives, sleeping pills, or anxiolytics (305.40), sedatives, sleeping pills, or anxiolytics Anxiety poisoning (292.89) 'Sedatives, sleeping pills, or anxiolytics withdraw (292 °), sedatives, sleeping pills, or anxiolytics with insanity, tranquilizers, sleeping pills, or anxiolytics withdrawing psychosis, tranquilizers , Sleeping pills or anxiolytics L: \ menu \ Pending-93 \ 93544.doc -20-200530188, persistence and rescue of dysmenorrhea with f birth sedatives, sleeping pills or anxiolytics-tincture sleeping pills Or anxiolytics, sedatives, sleeping pills, or anxiolytics, mood disorders, tranquilizers, sleeping pills, or anxiolytics, anxiety disorders, sedatives, sleeping pills, or anxiolytics, Sleep disorders caused by agents, sleeping pills or anxiolytics and unspecific sedatives, sleeping pills or anxiolytics-related disorders (292 · 9) 'Multiple substance-related disorders, such as multiple substance dependence (304 · 80) and Disorders related to other (or unknown) substances, such as anabolic steroids, nitrate inhalers and nitric oxide; sleep disorders include major sleep disorders such as: sleep disorders such as major insomnia ( 397.42), major narcolepsy (307 · 44), narcolepsy (347), respiratory-related sleep disorders (780.59), all-day physiological clock sleep disorders (30.45), and non-specific sleep disorders (307.47); Major sleep disorders, such as: narcolepsy, such as: nightmares (307 · 47), sleep panic disorders (307.46), sleepwalking disorders (307.46), and other specific sleep disorders (307.47); and Sleep disorders related to another psychiatric disorder, such as ... Another insomnia related to psychiatric disorders (307.42) and another narcolepsy related to psychiatric disorders (307.44); sleep disorders due to general medical conditions; and Substance-induced sleep disorders, including Insomnia type, narcolepsy type, narcolepsy type and mixed type; eating disorders such as: anorexia nervosa (307.1), including the subtypes of restricted and bulimia / diarrhea; neurological eating disorders (3. 7.51), including subtypes of diarrhea and non-diarrhea; obesity; forced eating disorders; and unspecific eating disorders (307.50); autism (299.00), lack of attention / hyperactivity disorders, including Lack of attention L: \ menu \ Pending-93 \ 93544.doc -21-200530188 Italian (3ιΓ〇〇 ^ (314.〇1), lack of attention / hyperactivity is obviously not noticed •, lack of attention / hyperactivity Dynamic compulsive (314.01) and no lack of attention 7 hyperkinesia (314.9) times _; motor function is charged ° boat behavioral disorders, such as: behavioral disorders, including early onset (21.81), adolescent onset (312.82) and not Specific start (312.89) sub-types, resistance to challenge disorders (313 · 81) and non-specific disruptive behavior disorders 'and Tic disorders', such as: Toure (s) disorders (Chuan 7.23); personality disorders , Including paranoid personality disorder (301.0), schizophrenic personality disorder (301.20), schizotypal personality disorder (3 () 1 · 22), social personality disorder (301.7), marginal personality disorder (301.83), dramatic personality disorder (301.50), narcissistic personality disorder (301.81), avoidant personality disorder (301.82), dependent type Subtypes of personality disorder (3016), delusional forced personality disorder (3014) and unspecified personality disorder (301.9); 15 20 Cognitive enhancement includes treatment of cognitive impairment in other diseases, the disease Such as: schizophrenia, bipolar disorder, depression, other psychiatric disorders, and mental symptoms related to cognitive impairment, such as: Alzheimer's disease, and φ sexual dysfunction includes sexual desire disorders, such as: low sexual desire disorder (302.71) and Sexual dislike disorders (302.79); sensory disorders such as: female sensory disorders (302.72) and male erectile disorders (302.72); organ orgasm disorders such as: female organ orgasm disorder (302.73), male organ orgasm disorder (302.74) and advance Ejaculation (302.75); Sexual pain disorders, such as: pain during intercourse (302.76) and vaginal spasms (306.51); non-specific sexual dysfunction (302.70); wrong sexual desire, such as: nudity (302.4), fetishism (302.81 ), Contact wear (302.89), pedophilia (302.2), sexual masochism (302.83), sexual sadism (302.84), transvestite L: \ menu \ Pending-93 \ 93544.doc -22- 200530188 fetishism (302.3), voyeurism (302 · 82) and non-specific sexual desire inversion (302.9), gender identity disorders, such as children's gender identity disorders (306) and adolescent or adult gender identity disorders (302.85); and not specifically sexual dysfunction (302.9). 5 All the various forms and sub-forms of mental disorders mentioned herein are considered part of the present invention. "Treatment" includes prevention, where this is appropriate for the relevant symptoms. Those skilled in the art will understand that according to the present invention, 7- [4- (3-fluorobenzyl-benzyl) -benzenesulfonyl] -8-fluorenoxy-3-fluorenyl-2,3 , 4,5-Tetrahydro-111-3_benzene nitrogen ίο hü, or its salts or solvates, can be used in combination with one or more other therapeutic agents' the agent such as: ΗΤ3 antagonist, serotonin Accelerators, NK-1 antagonists, selective serotonin reuptake inhibitors (8: 5111), noradrenaline reabsorption inhibitors (SNRI), non-selective reabsorption of one or more serotonin Inhibitors, norepinephrine and epinephrine, 15 CRF-1 antagonists, tricyclic antidepressants, dopaminergic antidepressants, H3 antagonists, 5HT1A antagonists, 5HT1B antagonists, 5HT1D Lu antagonists, 5HT4 partial accelerators, D1 accelerators, Ml accelerators, anticonvulsants, non-steroidal anti-inflammatory drugs (NSAIDs) and / or cyclooxygenase_2 (COX-2) inhibitors. 2) It should be understood that the combination or composition of the compounds may be administered simultaneously (in the same or different pharmaceutical formulations) simultaneously, separately or continuously. Suitable 5HT3 antagonists that can be used in combination with the compounds of the present invention are, for example, one or more chemicals selected from ondansetron, granisetron, and metoclopramide. L: \ menu \ Pending-93 \ 93544.doc -23- 200530188 Suitable serotonin promoters that can be used in combination with the compounds of the present invention include, for example, selected from sumatriptan, rauwolscine , Yohimbine and oxyclopramide. 5 Suitable SSRIs that can be used in combination with the compounds of the present invention include, for example: selected from fluoxetine, citalopram, femoxetine, fluvoxamine , Paroxetine, indalpine, setraline, and zimeldine. 10 Suitable SNRIs that can be used in combination with the compounds of the present invention include, for example, one or more chemicals selected from venlafaxine and reboxetine. Suitable tricyclic antidepressants that can be used in combination with the compounds of the present invention include, for example, selected from the group consisting of imipramine, amitriptiline, chlomipramine, and nortriptyline ( nortriptiline). _ Suitable dopamine-based anti-anxiety agents ' that can be used in combination with the compounds of the present invention include, for example, one or more chemicals selected from bupropion and amineptine. 20 Suitable anticonvulsants which can be used in combination with the compounds of the present invention include, for example, one or more chemical hydrazones selected from the group consisting of divalproic acid (divalproex), carbamazepine and diazepam. Suitable NSAIDs that can be used in combination with the compounds of the present invention include, for example, selected from ibuprofen, aspirin, and its active metabolite, Hyaluronic L: \ menu \ Pending-93 \ 93544.doc -24- 200530188 One or more chemicals of sour vinegar. Suitable COX-2 inhibitors that can be used in combination with the compounds of the present invention include, for example: rofecoxib (available under the trade name VIOXX⑧, from Merck, US Patent No. 5,474,995), celecoxib 5 ) (Obtained under the trade name CELEBREX⑧ from Pfizer, US Patent No. 5,466,823), valdecoxib (obtained under the trade name BEXTRA⑧ from Pfizer, US Patent No. 6,633,272), etoricoxib (obtained under the trade name ARCOXIA® From Merck, U.S. Patent No. 5,861,419); lumiracoxib (available under the trade name οο PREXIGE® from Novartis); paracoxib (U.S. Patent No. 5,932,598); COX-189 from Novartis; BMS347070 from Bristol Myers Squibb; tiracoxib ( JTE522) from Japan Tobacco; ABT963 from Abbott; CS502 from Sankyo; 2- (4-ethoxyphenyl) -3- (3-oxanesulfonylphenyl) -pyrazole 15 n, 5-b] pyridazine (GlaxoSmithKline) and 2-butoxy-4- [4- (methylsulfonyl) phenyl] -6- (triImethyl) pyridine (GlaxoSmithKline). Compounds of formula (I) and their pharmaceutically acceptable salts and solvates are also suitable for combination with other general and non-general antipsychotic agents to provide improved treatment of mental disorders. Special advantages associated with the combination, use, and treatment of compounds of formula (I) and their pharmaceutically acceptable salts and solvents, including equivalent or improved efficacy at doses lower than those typically used for the individual components. Positive treatment for mental disorders, and / or negative symptoms, and / or improved treatment of cognitive symptoms can also be observed. The combination, use and treatment method of the present invention can also be treated with certain antipsychotic agents (also known as antischizophrenic agents) and L: \ menu \ Pending.93 \ 93544.doc -25- 200530188 without proper Provides advantages in the treatment of responsive or resistant patients. The combination therapy of the present invention may be an adjuvant administration. Auxiliary administration is the administration of each component in the form of a separate pharmaceutical composition or device as an overlapping or overlapping administration. The therapeutic administration of these two or more therapeutic agents is generally referred to by those skilled in the art and is here an adjuvant therapeutic administration; it is also known as an additional therapeutic administration. It is within the scope of the present invention in which the patient receives any but all therapeutic therapies in which the compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof is administered separately, but in an overlapping or overlapping manner, and at least one antipsychotic agent. in. In a specific embodiment of the adjuvant therapeutic administration described herein, the patient is generally stabilized during the therapeutic administration of one or more components over a period of time, and then receives administration of the other components. The compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof may be administered as an adjuvant therapeutic treatment to a patient receiving at least one anti-disease agent. Patients who accept medicines as salts or solvates are acceptable for medicine, and do adjuvant therapeutic administration of at least one antipsychotic agent. The combination therapy of the present invention can also be administered simultaneously. Simultaneous administration means a time-of-day treatment in which the ingredients are administered, either in the form of a single-medicine composition or device containing two components, or simultaneous administration of separate components or devices each containing one of the components. The daggers and combinations of the respective components for simultaneous combination can be provided in the form of kit-of-parts. 'Therefore, in another aspect, the present invention provides a method for treating mental disorders: a method of administering a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof to a therapeutic administration of at least one antipsychotic agent Sexual and happy patients. In another aspect, the present invention provides the use of a compound of formula (I) or L: \ menu \ Pending-93 \ 93544.doc -26- 200530188. The use of a salt or solvate for the manufacture of auxiliary therapeutics 2 ί Lepin, used to treat mental disorders in patients receiving at least one antipsychotic agent for therapeutic administration. The present invention further provides a compound of formula (I) or /, an acceptable salt or solvate of 4 for use in adjuvant therapeutic administration, and / or oral treatment of mental disorders in patients receiving at least one antipsychotic agent for therapeutic administration. . In one aspect, the present invention provides a method for treating mental disorders by administering at least one antipsychotic agent as an adjuvant therapeutic agent to a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. Patients for therapeutic administration. In another aspect, the present invention provides the use of at least one antipsychotic H-agent for the manufacture of a medicinal product for the treatment of mental disorders, which is receiving a compound of formula (I) or a pharmaceutically acceptable salt or / Treatment of patients with cereals. The invention further provides at least one antipsychotic agent for adjuvant therapeutic administration for the treatment of mental disorders in patients receiving therapeutic administration of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof. In another aspect, the present invention provides a method for treating mental disorders by combining a compound of formula VII or a pharmaceutically acceptable salt or solvate thereof with at least one antipsychotic agent on the same day. The present invention further provides the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, and at least one antipsychotic agent combination, for the manufacture of a medicinal product for the simultaneous treatment of mental disorders. The present invention further provides the use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof for the manufacture of medicines for the treatment of mental disorders with the simultaneous administration of at least one antipsychotic agent L: \ menu \ Pending-93 \ 93544. doc -27- 200530188. The present invention further provides a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, for the simultaneous therapeutic administration of at least one antipsychotic agent to treat mental disorders. The present invention further provides the use of at least one antipsychotic agent for the manufacture of a medicinal product for the therapeutic administration of a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof for the treatment of mental disorders. In another aspect, the present invention provides a method for treating mental disorders by 'concurrently administering a pharmaceutical composition comprising a compound of formula (1) or a pharmaceutically acceptable salt or solvate thereof, and at least one mood stable Calling or anti-manic agent; a pharmaceutical composition comprising a compound of formula (1) or a pharmaceutically acceptable salt or solvate thereof, and at least one mood-stabilizing or anti-manic agent; use of a pharmaceutical composition, the composition The substance comprises a compound of the formula (I) or a pharmaceutically acceptable salt or solvate thereof, and at least one mood-stabilizing or manic agent for the manufacture of a medicament for the treatment of mental disorders; and a medicinal composition comprising the compound of the formula (I) or a pharmaceutically acceptable Accepts salts or solvates, and at least one mood-stabilizing or anti-manic agent for the treatment of mental disorders. · In another aspect, the present invention provides a kit of parts for treating mental disorders, comprising a first dosage form comprising a compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, and one or more additional Dosage forms' each contain antipsychotic agents for simultaneous therapeutic administration. Examples of antipsychotic agents for use in the present invention include, but are not limited to, butanyl phenones, such as: Haloperidol, Piinozide, and Droperidol; Pantopazine Phenothiazines, such as: chloropromazine, thioridazine, mesorazine L: \ menu \ Pending-93 \ 93544.doc -28- 200530188 (mesoridazine), trifluoro Trifluoperazine, perphenazine, fluphenazine, thiflupromazine, prochlorperazine and acetophenazine; thioxanthene, such as thioxanthene : Thiothixene and chlorprothixene; thienobenzodiazepines; benzisoxazoles; dibenzothiazepines ); 卩 Mi urges ketones (imidazolidinones); benzene iso-sigma sigma-yuraz (benziso-thiazolyl_piperazines); three mouth Qin (triazine), such as: lamotrigine; 1〇 (dibenzoxazepines), such as: loxapine; Dihydroindolones, such as: molindone, aripiprazole, and derivatives with antipsychotic activity. The antipsychotic drug brand names and suppliers of the present invention are applicable. Examples are as follows: clozapine (obtained under the trade name COZARIL⑧, 15 from Mylan, Zenith Goldline, UDL, Novartis); olanzapine (obtained under the trade name ZYPREXA⑧, from Lilly); ziprasidone ( ziprasidone) (obtained under the brand name GEODON® from Pfizer); risperidone (obtained under the trademark name RISPERDAL⑧ from Janssen); fumarate (quetiapine) salt (under the trade name of 20) SEROQUEL® obtained from AstraZeneca); Shou Tingduo

(sertindole) (obtained under the trade name SERLECT⑧); amisulpride (obtained under the trade name SOLION⑧ from Sanofi-Synthelabo); piperidine (obtained under the trade name HALDOL® from Ortho-McNeil); capric acid Droperidol (obtained under the trade name HADOL L: \ menu \ Pending-93 \ 93544.doc -29- 200530188 decanoate®); haloperol lactate (obtained under the trade names HADOL® and INTENSOL®); chlorpromazine (Chlorpromazine) (obtained under the trade name THORAZINE® from SmithKline Beecham (GSK); Flufenazine (obtained under the trade name PROLIXIN⑧ from Apothecon, 5 Copley, Schering, Teva and American Pharmaceutical Partners,

Pasadena); Fluphenazine decanoate (obtained under the trade name PROLIXIN decanoate®); Flufenazine heptanoate (obtained under the trade name PROLIXIN®); Fluphenazine hydrochloride (under the trade name PROLIXIN⑧) Obtained); Thiolsulfan thioxanthone (available under the trade name NAVANE⑧10, from Pfizer); sulfathionm thioxanthium hydrochloride (trademark NAVANE®

Obtained); trifhiperazine (10- [3- (4-methyl-1-piperazinyl) propyl] -2- (trifluoromethyl) phenothiazine diargonate, Trade name STELAZINE®, obtained from SmithKline Beckman); chlorophene 17 (obtained under the trade name TRILAFON®, from Schering); and chlorophenazine and 15 amitriptyline hydrochloride (under the trade name ETRAFON TRILAFON® Obtained); Methionazine (obtained under the trade name MELLARIL⑧ from var from Norvartis, Roxane, HiTech, Tava, and Alpharma); morphinone (obtained under the trade name MOBAN㊣ from Endo); morphindone hydrochloride (Obtained under the trade name MOBAN®); losapine (obtained under the trade name 20LOXITANE⑧ from Watson); losartin hydrochloride (obtained under the trade name LOXITANE⑧); and losartin succinate (under the trademark Obtained under the name LOXITANE®). Furthermore, benperidol (Glianimon®), perazine (Taxilan⑧) or melperone (Eunerpan®) can be used. 〇L: \ menu \ Pending-93 \ 93544.doc -30- 200530188 The antipsychotic drugs of Octasil ¥ include promazine (obtained under the trade name SPARINE⑧), trifluproniazine (obtained under the trade name vESPFim®), chlorine普 嗔 师 hl〇rpr〇thixenex (obtained under the trade name TARACTAN 氟), droperidol (obtained under the trade name 5 INAPSINE⑧), perphenazine (obtained under the trade name TINDAL⑧), prochlorazine (under the trade name COMPAZINE® (Obtained), methotnmeprazine (obtained under the brand name NOZINAN⑧), pipotiazine (obtained under the brand name pip〇TRIL⑧), iperidone, ° Dimir and tripentine (flupenthixol). 10 In another aspect of the present invention, suitable antipsychotic drugs include: olanzapine risperidone, thiothalcop, ar-prazole, flupineol, clozaphal, ziprasid Ketones and osanetant. -For pharmaceutical use, the compounds of the invention are usually administered as standard pharmaceutical compositions. Therefore, another aspect of the present invention provides a pharmaceutical 15 composition comprising a member selected from the group consisting of 1 [4- (3-fluoroyl-4-methyl-benzyl) -benzenesulfonyl] -8-methoxy-3- Fluorenyl-2,3,4,5_tetrahydro] n each benzonitrile and its pharmaceutically acceptable ^ and a pharmaceutically acceptable carrier. The pharmaceutical composition can be used to treat any of the symptoms described herein. μ, the compound of the invention can be administered by any conventional method, such as oral, 20 parenteral (eg, intravenous), buccal, sublingual, nasal, rectal or transdermal, and therefore the pharmaceutical composition is acceptable. ', = The aforementioned compounds of the present invention and their active pharmaceutically acceptable salts can be formulated into liquids or solids when taken orally, such as syrups, suspensions or emulsions, tablets, capsules, and lozenges. … L: \ menu \ Pending-93 \ 93544.doc • " 31- 200530188 Liquid formulations usually consist of the compound or a pharmaceutically acceptable salt, in the form of a suspension or solution in a suitable liquid carrier, the liquid carrier For example: aqueous solvents, such as: water, ethanol, or glycerol; or non-aqueous solvents, such as: polyethylene glycol or oil. The formulation may also contain suspending, preservative, flavoring or coloring agents. 5 Compositions in the form of tablets may be prepared using any suitable pharmaceutical carrier conventionally used in the preparation of solid formulations. Examples of such carriers include magnesium stearate, starch, lactose, sucrose and cellulose. Compositions in the form of capsules can be prepared using conventional capsule filling procedures. For example: tablets containing active ingredients can be prepared using standard carriers and then filled into hard capsules; in addition, dispersions or suspensions can be prepared using any suitable pharmaceutical carrier, such as hydrocolloids, celluloses , Fossilates or oils' and then the dispersion or suspension is filled into a soft gelatin capsule. The general non-gastrointestinal composition is composed of a solution or suspension of the compound or a pharmaceutically acceptable salt in a water-resistant or non-gastrointestinal acceptable oil. Polyvinyltetrahydroone, each ketone, imprint fat, peanut oil or sesame oil. Alternatively, the solution may be dried and then reconstituted with a suitable solvent before administration. The composition for nasal administration can be easily formulated into aerosols, drops, and gums. The powdered meal air preparation generally contains a solution or a fine suspension of the active substance in a pharmaceutically acceptable aqueous, non-aqueous formulation, and It is usually presented in a single or in a dosage form in a closed container in a sterilized form, which can be used or refilled and used with an aerosol device. In addition, the closed volume can be a unit dispersing device, such as: a single-nasal inhaler, or an aerosol disperser equipped with a meter valve, which is intended to lose L when the contents of the container are exhausted: \ menu \ Pending-93 \ 93544.doc -32- 200530188 abandoned. Where the dosage form includes an aerosol disperser, it will contain a propellant, which may be a shrinkable gas, such as compressed air, or an organic propellant, such as chlorofluorocarbons. The aerosol dosage form may also be in the form of an aerosol device. Compositions suitable for buccal or sublingual administration include tablets, lozenges, and bonds 5 4. The active ingredients of the towel are formulated with carriers such as sugar and ala_, goat gum or gelatin, and glycerin. The composition for rectal administration is conveniently in a finely divided form and contains a conventional suppository base ' such as coconut cream. Compositions suitable for transdermal administration include ointments, gums, and patches. The 10 composition is suitably in a unit dosage form such as a tablet, capsule or ampoule. The compound of this medicine is acceptable compound, usually (for adult patients). The dose is taken, for example: the oral dose is between mg and mg, such as between 1 mg and 150 mg, Such as: between 2 mg and 100 mg, such as: between 2 mg and 50 mg; or intravenous, subcutaneous or 15 intramuscular doses between 0.1 mg and _ mg, such as: (U Between mg and 50 ^ g, for example: 7 mg-methyl-methyl 4-methylbenzyl), i.e., benzodiamidinyl] _8_methoxy_3_methyl_2,3,4, 5-tetrahydro 1H-3-benzene nitrogen ^ or medical consultation to accept salt, calculated based on free test, the compound is administered 1 to 4 times a day. Suitably, the compound is administered for a period of 20 consecutive treatments, such as one week or more. Biosensors and D3) Glycerol on the receptor _4_fluorenyl_benzyl) _benzylsulfonyl] _8_fluorenyloxy_3_methyl L: \ menu \ Pending-93 \ 93544 .doc -33- 200530188 Tetra-2,3,4,5-tetrahydro_out_3-benzazepine, or its salt or solvate, is capable of selectively targeting human D2 / D3 dopamine receptors, which can be measured For slow bend ^: the combination of the body to confirm. The number of test compound pairs (Ki) bound to the human D2 / D3 dopamine receptor in the CHO cells by [125I] -Idodol SUlpride was measured as follows. The cell line was shown to be free of bacterial, fungal, and mycoplasmal contamination, and each mother liquor was stored frozen in liquid nitrogen. Cultivate monolayer or suspension in standard cell culture medium. Cells were recovered by scraping off or centrifugation (from suspension culture), and washed two or three times with a suspension of phosphate in saline, followed by centrifugation. Cells were stored frozen at ⑽ 10 ° C. The crude cell membrane was prepared by homogenization, followed by high-speed centrifugation, and Φfield shoot ligand binding was used to achieve the identification of the selected receptor. Preparation of cell membranes: Cell pellets were thawed gently at room temperature and resuspended in approximately 20 volumes of ice-cold extraction buffer: 50 mmol ^ 15 EDTA, 50 mmol TRI Pre-set crystals (pH 7.4@37 C), 1 mM MgCl2, 5 mM KC1, and 120 mM NaC suspension were homogenized using Ultra_Turmx for 15 seconds at full speed. The homogenate was centrifuged in a Sorvall RC5C centrifuge at 18,000 revolutions per minute at 4 ° C. The decantation was discarded and the homogenate was resuspended in extraction buffer 20 and centrifuged repeatedly. Finally, the tablets were resuspended in Trizma at a concentration of 50 millimoles in a preset crystal (ρΗ7.4·37@〇°), and in a 1 ml portion of the test tube, _8 (stored at TC 2 = 0.3 to 08 cells, D3 = 7 〇e + 〇7 cells, and D4 = 1.0E + 08 cells). Protein content was measured using BCA specifications and bovine serum protein as standards (Smith, ρκ • et al., Using L: \ menu \ Pending -93 \ 93544.doc -34- 200530188 Measurement of protein using bicinchoninic acid (Anal · Biochem · 150, 76-85 (1985)). Binding experiment: crude D2 / D3 cell membrane 〇 · 〇3 nanomolar concentration 5 [125I] _I〇dosulpride (~ 2000 Ci / mmole; Amersham, UK ·) culture

The test compound contains Trizma containing 50 millimolar concentration (pH 7.4@37°〇, 120 millimolar concentration NaCl, 5 millimolar concentration ^ 1, 2 millimolar concentration 〇3 (: 12.1 millimolar concentration] ^ 02, 0.3% (weight / volume) in bovine serum protein buffer. The total volume is 0.2 ml, and cultured in a 37 ° C water bath for 40 minutes. Continued, Sample in GF / B

Filtered on Unifilters using Canberra Packard Filtermate, and washed four times with ice-cooled Trizma at a pre-set crystallization solution (pH 7.4@37 C). Fortunate shooting on the filter was measured using a Canberra Packard Topcount Sinitillation counter. Non-specific binding is defined by a concentration of 15 to 10 micromolar SKF-102161 (YM-09151). For the competition curve, 10 consecutive cold-drug competing drugs were used (dilution range: 10 mM mol 7 ° C-10 nanmole concentration). The competition curve uses a bending curve analysis, an iterative curve fit program in Excel. Results are expressed as pKi values, where pKi ^ logli ^ Ki] 〇 20 exemplary compounds have a pKi value of 28.0 at the dopamine D3 receptor. Exemplary compounds have a pKi value > 7.0 at the dopamine D2 receptor. Binding experiments on lightly-selected 5-HT6 receptors Compounds can be tested following the procedures outlined in WO 98/27081. The L: \ menu \ Pending-93 \ 93544.doc -35- 200530188 shows that the exemplary compound has a pKi value d.o at the serotonin 5-ΗΤ6 receptor. In vivo binding experiments Compounds can be tested following the procedures outlined in WO 94/04533. It is shown that the exemplary compound has a PKi value of 28 · 0 on the serotonin 5-HT2C receptor and> 8.0 on the serotonin 5-HT2A receptor. [Embodiment] The present invention is further illustrated by the following non-limiting examples. 1〇 Description 1 1- (4-Bromo-phenyl) -1- (3-imidyl-4-methylphenyl) -methanol (D1) dried magnesium filings (4.24 g, 0.55 Millimoles) with a heavy stir bar under argon for 16 hours. Several iodine crystals were added, followed by a solution of 4-bromo-2-fluorobenzylbenzene (94.5 g, 0.5 15 mmol) in tetrahydrofuran [THF] (200 ml). This addition takes place in about 40 minutes and the solution is allowed to reflux during the addition. The resulting solution was stirred for 1 hour. 4.Bromobenzaldehyde (71.7 g, 0.39 mmol) in THF (200 ml) was cooled to 0 ° C and then treated with the above-mentioned Greener's solution. The addition of the Grignard solution was performed within 30 minutes, and the resulting solution was stirred at room temperature for 2 hours. The 20 reaction mixture was slowly added to a potassium sodium tartrate solution (10% solution, 1 liter) and extracted with ethyl acetate (EtOAc). The organic solution was dried over brine and sodium sulfate and evaporated. Trituration with hexane gave the title product (Dl) (71.8 g, esycO ^ H-NMRSMCDCh) as a white solid 2.20 (1), d), 2.24 (3Η, m), 5.75 (1Η, d) , 6.98 (m, s), 7.05 (1Η, m), 7.16 (1H, m), L: \ menu \ Pending-93 \ 93544.doc -36- 200530188 7.24 (2Η, m), 7 47 (2Η, m). Narrative 2 M4-Methynylphenylfluorene_ (3_M_4_ψylbenzyl) _methylbenzene_

Glycol, 0 072-benzyl M- (3 · amino + methylphenyl) _fluorenol (21.4 10 15

Imitation noo ancient 2 dia), triethylsilane (34 g, 0.29 mmol) and chlorinated pentol) were cooled in an ice bath. Add 3 I formazan stone Yin, ^ (7Please '〇.78mmol) in 3G minutes. The solution was worked for one hour, and then washed with a saturated sodium bicarbonate solution and brine. The solvent was removed under reduced pressure, and the residue was distilled. Triethylsilanol was first distilled Bp (75 ° c @ 2 mmHg). The title product (D2) was distilled Bp (125-132°C@0.15 mmHg). Yield (16.4 g, 82%). h-NMRSfKCDChyapH, !!!), 3.86 (2Η, s), 6.8 (2Η, m), 7.0 (3Η, m), 7.4 (2Η, m). Convergence of 3 8-fluorenyl-3-fluorenyl-2,3,4,5-tetrafluorenazil-7-sulfofluorenyl fluoride (D3)

L: \ menu \ Pending-93 \ 93544.doc -37- 200530188 a) 7-methoxy_3_fluorenyl · 2,3,4,5-tetrahydro_1ug-3_benzene nitrogen 7-Methoxy-2,3,4,5_tetrahydrobenzonitrile hydrochloric acid in ethyl chloride (250 ml) (see European Patent No. 285287) (25 g, 125 mol) and 37% formma Lin (25 ml) of the mixture was treated with sodium triacetoxyborohydride (30 g, 250 mol) and the internal temperature was kept below 2000c. After stirring for 2 hours, water was added and the pH was adjusted to 10 using a 50% sodium hydroxide solution. The organic layer was separated, dried over sodium sulfate, and evaporated to dry product (23 g). ^ b) 8-methoxy-3_methyl-2,3,4,5_tetramethyl-1,3-benzazine_7-carboxylic acid The product from part (a) is dissolved in trifluoro Methyl acetate (125 mL) and then add chloroacetic acid (16.5 mL, 250 mmol) dropwise while stirring in an ice bath. The solution was stirred for 30 minutes and then evaporated to dryness to give the title luteinic acid 'which was used directly in the next step. c) 8-methoxy-3_methyl-2,3,4,5-tetrahydro-1 where 3_benzonitrile_7-jibenzyl radical is derived from the lutein acid in part (b) is dissolved in Sulfuryl chloride (75 ml) and refluxed for 30 minutes. After cooling, the 'solution was evaporated to dryness, producing the title sulfonyl group gas, which was used directly in the next step. Phenyl-8-methoxy-3-methyl-2,3,4,5-tetrahydro_1ug-3-3benzyl sulfolium fluorenyl fluoride is derived from the fluorenyl chloride in part (c) and is dissolved in acetonitrile ( 500 ml), L: \ menu \ Pending-93 \ 93544.doc -38-200530188 and potassium fluoride (37 g, 625 mmol) and 18-crown-6 (1 crystal) were added. The mixture was stirred for 18 hours, then the reaction was stopped with a cold aqueous sodium bicarbonate solution until the pH was equal to 8. The mixture was extracted twice with ethyl acetate, washed with bicarbonate solution, then brine, dried and evaporated to give the sulfofluorenyl fluoride (D3) (25 g ^ MH + 274, h-NMR ^ HPMSO-d6) 2 · 3 (3Η, s), 2.61 (4Η, m), 3.03 (2Η, m), 3.97 (3Η, s), 7.29 (1Η, s), 7.69 (1Η, s ). Narrative 4 7- (4-Methylbenzyl fluorenylmethoxy-3 · methyl_2,3,4,5-tetrahydrobenzene nitrogen (D4)

0, 0 Trifluoromethanesulfonic acid (8.8 ml) was added to trifluoroacetic acid 4-bromobenzenesulfonyl chloride (25 g, 97 ml) in trifluoro 15 acetic acid (60 ml) under nitrogen pressure. 8 mmol) and indium chloride (1.44 g, 6.5 mmol). The resulting mixture was heated under reflux for 24 hours, then cooled, diluted with dichloromethane (200 mL), and methanol (100 mL) was added to maintain the temperature below the pit. Dove (w / v) aqueous sodium hydroxide (200 ml) was added to the palpitate 12 within 1 hour, maintaining the temperature below the pit, and phase separation. The aqueous phase was extracted with two-gas simmer (60 liters) and the combined organic phases were washed with water and EtOAc and diluted with isopropyl acetate (3 mL). The solution was steamed in a vacuum chamber, L: \ menu \ Pending-93 \ 93544.doc -39- 200530188 and the resulting slurry was cooled to room temperature and stirred for 4 hours. The solid was filtered, washed with isopropyl acetate (40 mL), and dried at 40 ° C under vacuum to give the title product (19 g) as a white solid. Mp 161-163 ° C; MH + 410 and 412, 1H-NMR δΗ (400 megahertz, DMSO-d6) 2 · 25 (3Η, s) 5 2 · 40-2 · 50 (4Η, m), 2 · 85-2.95 (4Η, m), 3.72 (3Η, s), 7.00 (1Η, s) 5 7.72 (1Η, s), 7.80 (1Η, s). Example 1 7- [4- (3-Fluoro-4-methyl-benzyl) -phenylphenanthryl] _8_methoxy_3_methyl_2,3,4,5_tetrahydro_1fan 3_Benzazine (£ 1) xxtxdco-⑹a / 0A0 ^ (i) Benzyl group (phenyl group) in dry tHF (300 ml) small (3_air group 15 permethenylphenyl group) · Nail (D2) (46.45 g, 166.6 mmol) was mixed, and the solution was added dropwise at a temperature of -78 ° C under argon pressure. , 66.5 ml, 166.4 mmol). Add 8_Methoxy_3_methyl_2,3,45_tetrachlorobenzylpyridin-7-continylfluorofluorene (15 '' 6 g, 55.47 m. Before), the resulting 20 solution was stirred at -78 ° C for 30 minutes. The addition took place within 20 minutes. The resulting red solution was stirred, and then the reaction was stopped with acetic acid (ig ml) L: \ menu \ Pending-93 \ 93544.doc -40- 200530188. The mixture was diluted with water (200 ml) and allowed to warm to room temperature. The pH was adjusted to greater than 7 using a saturated sodium bicarbonate solution and extracted with EtOAc (2 x 300 mL). The combined organic phases were washed with water, brine, and dried over magnesium sulfate, then concentrated to an oil. This oil was analyzed using a column chromatography 5 layer, and was purified by purification on silica with 10% methanol-dichloromethane (0 to 0% ammonia) to give an off-white solid (23.0 g). For further purification, an amine-based column was used. Layer analysis was performed with EtoAc extraction in hexanes from 0 to 1000/0. This resulted in the title compound (E1) as a white solid, free base (18.3 g, 73%). MH + 454. 1H-NMR SH (CDC13) 2.22 (3Η, s), 2.36 (3Η, IOs), 2.48-2 · 8 (4Η, m), 2.85 · 2 · 99 (4Η, m), 3.73 (3Η, s), 3.96 (2Η, s), 6.63-6 · 84 (2Η, m), 7.03-7 · 12 (1Η, t), 7.20 -7 · 29 (3Η, m), 7.80 (1Η, s), 7.85_7 · 93 (2Η, d). Example 2 15 7- [4- (3_Fluoro_4_methyl-section) ) -Benzenesulfonyl} -8-methoxy-3-fluorenyl-2,3,4,5_tetrahydro_1K-3-benzylhydrochloride (£ 2)

For 7- [4- (3-Fluoro-4-methyl-benzyl) -benzene-20 sulfofluorenyl] -8-methoxyethoxymethyl 2,3 in dichloromethane / methanol, A solution of 4,5-tetrahydro-111-3-benzazepine (£ 1) in free base (18 · 3 g, 73%) with HC1 (1 mole concentration in ether, L: \ menu \ Pending -93 \ 93544.doc -41-200530188 40.3 liters, 40.3 mols). Evaporation and subsequent trituration with ether gave the title compound (19.52 g) as the mononitrogenate. ] ^ 11 + 454.111 ^] \ 411 5H (DMS〇-d6) 2.Π (3Η, s), 2.76 (3H, s), 2.80-3.60 (complex series of 8h multiplet), 3.72 (3H, s), 4.00 (2h, s), 6 9〇_7 〇1 (2H, _ 5 7 〇2 (1H, d), 7.19 (3H, recognized 7.44 (2H, d), 7.79-7 · 83 (3Η , M). Example 3 p-Phenylbenzoic acid 7- [4- (3-fluoro-4-methylpyridyl) _benzenesulfonyl] -8-methoxy-3_methyl-2,3 , 4,5_tetrahydro-1H_3-benzonitrile salt (E3)

10 S03 '12% w / w p-toluene acid solution in acetic acid (0.59 ml) was added to 7- [4 in a THF (2 ml) / ethyl acetate (2 ml) mixture -(3 · Fluoro-Φmethyl-benzyl) _benzenesulfonyl] _8_methoxy_3_fluorenylfluorene, sulfonium hydrogen- 丨 Phenylbenzyl sulfonate, Huaiye ^ Liquid quilt Species 15. Crystals and the solvent evaporated. The resulting solid surface was excess and dried under vacuum at 40 C 'to give the title product (E3) (0 18 g) as a white solid. Mp 202_204 c, 1H-NMR 3H (d6-DMSO, 600 megahertz) 2.17 (3Η, d), 2.30 (3H, s), 2.84 (3Η, d), 3.0 · 3 · 2 (6Η , M)? 3.60 (2Η, m), 3.73 (3Η, s), 4.01 (2Η, s), 6.97 (1Η, dd), 7.02 (1Η, d), 20 7 09 (1H, s), 712 (2H, d), 7.20 (1 (, t), 7.45 (2Η, d), 7.49 (2Η, d), 7.81 (2Η, d), 7 · 85 (1Η, s), 9.68 (1Η, brs). L: \ menu \ Pending-93 \ 93544.doc -42- 200530188 Table 1: p-Toluenesulfonic acid 7- [4- (3-fluoro-4-methyl · benzyl) -benzenesulfonyl]- X-Ray Powder Diffraction (XRPD) Angle and d Interval of 8-methoxy-3-methyl-2,3,4,5-tetrahydro-1le-3-benzepine salt. 5 Position [° 2T1l] d-interval [Angles] 3.5 25.5 9.6 9.2 11-2 7.9 11.7 7.6 13.6 6.5 15.1 5.9 15.9 5.6 16.3 5.4 16.9 5.3 17.5 ——- 5.1 17.9 5.0 18.2 4.9 18.8 4.7 19.2 ---- 1 4.6 20.2-^ __ 4.4 20.4 4.4 Position [° 2Th.] D-interval [Angstrom] 20.6 4.3 20.7 4.3 20.9 ~~ -__ 4.2 22.5 3.9 23.2 3.8 23.5 3.8 24 · 1 3.7 24.4 3.6 26.3 3.4 273 3.3 21.6 3.2 28.0 3.2 30.8 2.9 31.5 2.8

The data obtained from p-xenobactite xanthate are shown in Figures 1-3 and Table 1. L: \ menu \ Pending-93 \ 93544.doc -43- 200530188 Example 4 p-Toluene 7- [4_ (3 · decylbenzylmethyl) · benzylbib 8_methoxy-3- Fluorenyl-2,3,4,5-tetrahydro-1ug-3-benzazepine monohydrate pentyl 4)

10 15 Chlorotrimethylsilyl (66 μl, 0.52 mmol) was charged with zinc particles (1.23 g, 18, 75 mmol) in hydrogen squeaking (20.5 ml) and the suspension was Stir for 30 minutes. 3-Fluorobenzyl-benzyl molybdenum (15 7.5 millimoles) was added to the mixture within 15 minutes, maintaining a warm production at 20-2, and the reaction mixture was stirred at room temperature for 9 minutes. *bell. : Add (0) (5.8 mg, ο ,, mol) to (diphenylphosphine), and continue with 7_⑷bromobenzenesulfonyl) _8methoxy in tetrachlorobite (20.5 pen liters) _3_ Jiamei 2 compound was heated under reflux for 4 hours. The reaction mixture was cooled to 至 to 皿 'and a 50/0 wt / wt aqueous sodium bicarbonate solution (20.5 ml) was added. = Stir the dry mixture for 15 minutes, pass through Yin's salt, and separate the filtrate phase into ice. The organic handle should be 10% weight / weight aqueous sodium chloride solution (3 × 20.5 ml). 1 And ethyl acetate (20.5 ml) = the two organic phases served were combined and trithiocyanic acid (443 mmol. 25 mmol) at 18-25. Your Majesty Deals! hour. The suspension was filtered through L: \ menu \ Pending-93 \ 93544.doc -44-20 200530188's salt, and the filtrate was extracted with water (2 × 20.5 ml) and treated with p-toluenesulfonic acid monohydrate (952 The milligram, 5 ml / aqueous phase was combined and 5 was concentrated under vacuum, and the resulting slurry was cooled to room temperature. The product of the solution was filtered, washed with water (10.24 liters), and dried at 40 to 2 h. Drying to give the title product (E4) as a white solid (20.4 g under vacuum «198.5-200.5 ° C; ^ -NMR 5H (DMSO-d6) 2.18 (3H ^ s), 2.84 (3Η, d ), 2.95_3 · 65 (8Η, br m), 3.73 (3Η, s), 4 〇1 (2h (3H '6.96-7 · 04 (2Η, m), 7.11-7 · 14 (3Η, m), 7.18 (1Η, t), 7.45 ·; = (4H, m), 7.80-7 · 85 (3Η, dm, 9.70 (1Η, bi * s) 10 Table 2: p-Toluene acid 7- [4- (3-fluoroyl-4-fluorenyl-fluorenyl) _benzoylvinyl] alkoxy-3-fluorenyl-2,3,4, XRPD angle and d-interval of 5-tetrahydro-1private 3-benzyl nitrate monohydrate. Position [° 2Th.] D-interval [Angles] 3.3 27.1 9.4 9.3 10.4 8.5 11.7 7.5 13.7 6.5 15.7 5.6 16.0 5.5 17.5 5.1 Position P2T11.J d-interval [Angles] 22.0 4.0 22.4 4.0 23 .5 3.8 23.7 3.6 25.1 3.5 25.2 3.5 27.1 3.3 28.3 3.2

L: \ menu \ Pending-93 \ 93544.doc -45 200530188 17.8 5.0 18.6 4.8 18.9 4.7 19.6 4.5 19.8 4.5 20.1 4.4 21.1 4.2 21.3 4.2 28.4 3.1 29.4 3.0 29.7 3.0 31.5 2.8 31.6 2.8 33.1 2.7 By p-toluenesulfonic acid The data obtained from the salt monohydrate are shown in Figure 4-6 and Table 2. 0 X-ray powder diffraction 5 x_light powder diffraction (XRPD) analysis was performed on a Phillips x, pert Pr0 powder diffractometer using X ' Ceierator detector. The obtaining conditions are: radiation Cu κ, generator intensity: 40 kV, generator current: 45 mA, 'starting angle: 2.0.20, end angle: 40002θ, step size: 〇〇 167 2Θ 'Time per step: 31 · 75 seconds. The maleate and p-toluene salts are prepared using backfilling techniques. Maleic acid dihydrate and acid-acetic acid solvates were prepared using Shixi wafer technology. &man; Raman spectroscopy is recorded in an NMR tube using a Nicolet 960 esp, ft Raman spectrometer at 4 cm "resolution, from Nd: v〇4 laser L: \ menu \ Pending-93 \ 93544. doc -46- 200530188 Excitation (1064 nm) with a power output of 400 mW. For the purpose of spike selection, use an absolute starting point of 0.5 and a sensitivity of 65%. Differential Scan Card Meter (DSC) 5 10 15 20 Using the Thermal Analysis DSC Q1000, record the DSC temperature curve. The sample is heated at 1 (TC min-1, in an open disk. All publications cited in this manual include, but are not limited to Here, as a reference, if the respective publications are special # 疋 and each is indicated, here is incorporated as a reference as a reference. [Simplified illustration of the drawing] Figure 1 shows the preparation as described in Example 3. Of p-toluenesulfonic acid 7_ [4_ (3_, yl-4-methyl-yl_benzyl) _benzoxanthene] _8_methoxy_3methyl_2,3,4,5_tetragas 1 X-ray powder diffraction (xRpD) data obtained from han-3 diphenylazepine salt. For example, the p-toluene acid 7 described in Example 3 is made of (3_amino group_4_methylpyrene only) ] _8-methoxy Methyl_2,3,4,5-tetrahydro-1 private 3-benzene nitrogen is characterized by having an XRPD pattern roughly as shown in Table 1. As shown in Fig. 2, the member is not as good as described in Example 3. Preparation of p-toluenesulfonic acid 7 · [4- (3- ίΤ "4; methyl4-yl) ~ benzo-continyl] each methoxy · 3-methyl-2,3,4,5_tetra-lice Raman spectrum of -1fan 3-benzyl salt. As much as ^ 3 shows that p-toluene acid H4- (3-air ^^^^ phenylbenzene continued to be prepared as described in Example 3 [Methyl] dongmethoxy-3-methyl-2,3,4,5-tetrahydropyrene 3. Qianhu—DSC temperature curve. Figure 4 shows p-toluene acid 7_ [4_] prepared as described in Example 4. (3_ L: \ menu \ Pending-93 \ 93544.doc -47- 200530188 gas-4-amidino-benzyl) -benzoxanthenyl] -8-methoxy-3-methyl-2, X-ray powder diffraction (XRPD) data obtained from 3,4,5-tetrahydro-1 //-3-phenylazepine monohydrate. As described in Example 4, p-toluenesulfonic acid 7- [4 -(3-Fluoro-4-fluorenyl-benzyl 5-yl) -benzoxanthenyl] -8-fluorenyl-3-methyl-2,3,4,5-tetraaza-benzophenone * The salt monohydrate is characterized by an XRPD pattern with signals approximately as listed in Table 2. Figure 5 shows p-toluenesulfonic acid 7- [4 prepared as described in Example 4. -(3-fluorenyl-4-methyl-benzyl) -benzyl] -8-fluorenyl-3-fluorenyl-2,3,4,5-tetra-10 fluorene-1 //- Raman spectroscopy of 3-benzyl nitrate monohydrate. Figure 6 shows p-toluenesulfonic acid 7- [4- (3-fluoroyl-4-fluorenyl-benzyl) -benzenesulfonyl] -8-fluorenyl-3-fluorenyl prepared as described in Example 4. DSC temperature curve of -2,3,4,5-tetrahydro-1 //-3-phenylazepine monohydrate. It should be understood that the spectrum and diffraction data will vary slightly depending on different factors, such as the temperature, concentration and instrument used. Those skilled in the art will understand that the position of the XRPD peak will be affected by the difference in sample height. Therefore, the position of the peak referenced by # is an error of + Λ 0.15 degrees 2Θ. L: \ menu \ Pending-93 \ 93544.doc -48

Claims (1)

200530188 10. Scope of patent application: 1. selected from 7- [4- (3-fluoroyl-4-fluorenyl-benzyl) -benzenesulfonyl] -8-fluorenyl-3-methyl-2, 3,4,5-Tetrapyrene-1 仏 3-Benzazepine and one or more chemicals of pharmaceutically acceptable salts and solvates thereof. 5 2. Selected from toluenesulfonic acid 7- [4- (3-fluoroyl-4-fluorenyl-benzyl) -benzenesulfonyl] -8-methoxy-3_fluorenyl-2,3,4 1,5-tetrahydro-1K-3-benzonitrile salt and one or more chemicals thereof which are pharmaceutically acceptable solvates. 3. A medicinal composition comprising one or more chemicals in the scope of patent application No. 1 or the scope of patent application No. 2 and a pharmaceutical acceptable carrier. 4. Use one or more chemicals according to one or more of the scope of the patent application or the scope of the patent application for the treatment. 5. For the treatment of mental disorders according to one or more chemicals in the scope of patent application 1 or the scope of patent application 2. 15 6. —Use of one or more chemicals according to the scope of patent application 1 or the scope of patent application 2 for the manufacture of pharmaceuticals for the treatment of mental disorders. 7. · A method for treating mental disorders in mammals including humans, comprising administering an effective amount of a drug to a mammal in need thereof in accordance with any one of the patent application scope item 1 or the patent application scope item 2 One or more chemicals. L: \ menu \ Pending-93 \ 93544.doc -49-