JPS6231716B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is useful as a long-acting antipsychotic that has central nervous system depressant effects such as strong locomotor activity suppressing effect, anti-apomorphine effect, and conditioned avoidance reaction suppressing effect, and also has a long-lasting effect. , general formula This invention relates to a novel thioxanthene derivative represented by and a salt thereof. In the above formula, X is hydrogen, lower alkyl (methyl,
ethyl, propyl, butyl, pentyl, etc.), halogen (fluorine, chlorine, bromine, iodine, etc., preferably fluorine, chlorine, bromine), trifluoromethyl, -SR ¹ , -SO ₂ R ¹ , - SO ₂ N(R ¹ ) ₂ (here R ¹ is lower alkyl), Y is hydrogen or fluorine, Z is >N- or >CH-,
L is a group -OH,

【formula】

[Formula] (where R ² represents lower alkyl), and n represents 2 or 3. The dotted line in Ring A indicates that this moiety may form a double bond (ie, Ring A is a cyclohexane or cyclohexene ring). However, when Y is fluorine, X represents trifluoromethyl. The compound of general formula () is produced by the following method. Method 1 [In the formula, T represents a reactive active ester group, and examples thereof include halogen atoms such as chlor, bromo, and iodo, organic sulfonyloxy such as methylsulfonyloxy and para-toluenesulfonyloxy, and preferably chloro, bromo, and methyl. Sulfonyloxy, para-toluenesulfonyloxy. Other symbols have the same meanings as above. ] The method of the above reaction scheme can be carried out in the presence or absence of a suitable inert diluent, but it is preferable to use a diluent. As a diluent, alcohol solvents such as methyl alcohol and ethyl alcohol, ketone solvents such as acetone and methyl ethyl ketone, ether solvents such as tetrahydrofuran and dioxane, halogenated hydrocarbon solvents such as methylene chloride and chloroform, benzene, toluene, xylene, etc. aromatic hydrocarbon solvents, dimethylformamide, dimethylsulfoxide, hexamethylphosphoramide, N-methylpyrrolidone, and other aprotic polar solvents. Furthermore, in order to facilitate the reaction, it is preferable to use a suitable deoxidizing agent to remove by-produced acid. As the deoxidizing agent, either an inorganic base or an organic base can be used. As the inorganic base, sodium hydrogen carbonate, potassium hydrogen carbonate, lithium carbonate, calcium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, etc. are used. Alkali metal alkoxides such as sodium methylate, sodium ethylate, sodium tertiary butyrate, sodium acetate, etc. as organic bases;
Potassium acetate, triethylamine, pyridine, etc. are used. The reaction temperature is 10-200°C, and generally, if no diluent is used, the reaction temperature is 100-200°C. The reaction time varies depending on the diluent used and the reaction temperature, but is 30 to 72 hours. Method 2 [In the above formula, the symbols have the same meanings as above. ] The reaction may be carried out in the presence or absence of a suitable inert diluent, but preferably according to method 1.
It is preferable to use diluents such as those mentioned above (excluding ketonic solvents). The reaction conditions for Step 1 vary depending on the individual reaction, and are carried out in the presence of a diluent at a temperature ranging from room temperature to 200°C. , organic acids (such as para-toluenesulfonic acid), and other acids are used as catalysts. When isolating the intermediate (enamine) represented by the general formula (), it can be purified by removing diluents and acids in a conventional manner and performing operations such as distillation. If the intermediate (enamine) is not isolated, it can be subjected to subsequent contact or chemical reduction in the presence of the diluent used in the condensation, or with a suitable exchange of the diluent. As a catalyst for the catalytic reduction in step 2, metals such as palladium, platinum, rhodium, nickel, ruthenium, and cobalt are used with inert carriers such as activated carbon, alumina, barium sulfate, calcium carbonate, and strontium carbonate attached. be done. The reaction time depends on hydrogen pressure, reaction temperature, etc.
At atmospheric pressure and room temperature, it generally takes a long time. When the reduction is carried out chemically, an organic acid such as formic acid (or a derivative thereof) or a metal hydride compound is used. The former reductive amination reaction using formic acid is generally the Leucart reaction (Moore.ML: Organic
Reaction 5 , 301 (1949)), and the purpose can be achieved by adding formic acid to the compound of general formula () and keeping it at an appropriate temperature (generally high temperature). For reduction with metal hydride compounds, lithium aluminum hydride, lithium borohydride, sodium borohydride, borohydride (borane, diborane, etc.), sodium dihydro-bis(2-methoxyethoxy)aluminate, etc. Combinations such as lithium aluminum hydride-aluminum chloride, sodium borohydride-aluminum chloride, etc. are also used. When a double bond is present in ring A, a chemical reduction method is preferable to catalytic reduction. Method 3 [In the above formula, the symbols have the same meanings as above. ] In the method according to the above reaction scheme, the oxime formation in Step 1 is carried out in the presence of various suitable diluents in a conventional manner. The reduction reaction in step 2 is the same as step 2 in method 2.
and step 3 can be carried out according to method 1. The following methods 4 to 5 are applied to the production method when Z in general formula () represents a >N- group. Method 4 [In the above formula, the symbols have the same meanings as above. ] The compound of general formula () in the above reaction formula can be prepared by Method 1
Alternatively, it can be easily produced by Method 2. The reaction can be carried out according to Method 1. Method 5 [In the above formula, the symbols have the same meanings as above. ] The compound of general formula (XI) in the above reaction formula is easily produced from the compound of general formula (). The reaction can be carried out according to Method 1. Method 6 In this method, Z is >CH in the general formula ()
Applies to the manufacturing method when the group - is indicated. [In the above formula, the symbols have the same meanings as above. however
Hal represents a bromine or chloro atom, and m represents 1 or 2. ] The compound of general formula () in the above reaction formula can be easily produced by Method 1 or Method 2. In the method according to the above reaction formula, the reaction in step 1 is carried out using Wittig as usual.
Reactions (A. Maercker, Organic Reactions, 14 ,
270 (1965)) or
It is easily produced by reacting a Grignard reagent or an organolithium compound followed by a dehydration reaction. Note that as the solvent, ether solvents such as ether, tetrahydrofuran, and dioxane, and aromatic hydrocarbon solvents such as benzene, toluene, and xylene are used. Ether and tetrahydrofuran are preferred. Reaction temperature and reaction time vary depending on the individual reaction, but -30℃-150℃, 0.5
~10 hours is appropriate. The reduction reaction in step 2 can be carried out according to method 2. In the compound represented by the general formula (), optical isomers, diastereomers, or configurational isomers may exist. When the compound of general formula () is obtained as an optically inactive racemate, diastereomer or mixture of configurational isomers, the individual isomers can be resolved, if desired, by well-known methods. , can be manufactured separately. The base of general formula () produced by the above method can be made into pharmaceutically acceptable acid addition salts and quaternary salts. As acids for forming salts, inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and maleic acid, fumaric acid, succinic acid,
It can be appropriately selected from organic acids such as citric acid and tartaric acid. Examples of quaternary chlorinating agents include dimethyl sulfate, diethyl sulfate, methyl iodide, and ethyl bromide. According to the present invention, the compound represented by the general formula [] has a long-lasting central nervous system depressing effect, such as anti-apomorphine effect, methamphetamine effect, locomotor activity suppressing effect, and hexobarbital anesthesia enhancement. action, suppression of conditioned avoidance responses,
It has pharmacological activities such as habituation, slowing of spontaneous brain waves, and loss of righting reflexes, and is characterized by its longer action than haloperidol, pimozide, flupenthixol, or chlorprothixene.
Therefore, the compound represented by the general formula [ ] according to the present invention is useful as a long-acting medicine such as an antipsychotic, an anxiolytic, a sedative, a hypnotic inducer, an anesthesia inducer, and the like. The compound represented by the general formula [] was tested by the following method. The anti-apomorphine test was conducted in accordance with the method of Janssen, PAJ et al. (Arzmeim-Forsch, 17, 841 (1967)) using 7 to 14 female rats per group.
A compound represented by the general formula [] was orally administered to this, and 1 to 24 hours later, 1.25 mg/Kg of apomorphine was administered.
was administered intravenously, and the inhibition rate of gnawing behavior was determined 5 and 20 minutes later. 50% effective dose of each compound from inhibition rate at maximum effect, ED ₅₀
I found the value. As shown in Table 1, the compound represented by the general formula [] has a strong anti-apomorphine effect.

[Table] Using the ED ₅₀ values obtained in the anti-apomorphine test, the drug was orally pretreated at various times to examine the durability of the action. Table 2 shows that compounds represented by the general formula [], such as Example Nos. 1, 3, 5, 14, and 15, have a longer duration of action than haloberidol or flupenthixol in terms of anti-apomorphine action.

[Table] Anti-methamphetamine group toxicity test by Fink, G.
B. et al. [J.Pharmacol.exp.Ther.137, 361ff
(1962)]. 1 male mouse
Group 10 was used as group 10, and after being orally treated with the compound represented by the general formula [] at various times, they were placed in a plastic pot (200 cm ² , 18.7 cm height) and treated with 9 mg/Kg of methamphetamine. The mortality rate within 5 hours after intraperitoneal administration was determined. The ED ₉₀ value, which is the effective dose that allows more than 90% of the animals used to survive, was determined. As shown in Table 3, compounds represented by the general formula [], such as Example Nos. 1, 5, and 14, prevent the excitatory lethal effects of methamphetamine. The locomotor inhibition test was performed by Dews, PB [Brit.J.
pharmacol., 8, 46 (1953)]. Five male mice were used per group, and after being orally treated with the compound represented by the general formula [] at various times, they were placed in a metal box of 20 x 40 x 20 height (cm) in one group. The animals were placed in groups and their amount of exercise was measured for 20 minutes. The significance for the control group's exercise level is t
The minimum effective dose was determined by testing and expressed in MES. As shown in Table 3, the compounds represented by the general formula [ ], such as Example Nos. 1, 5, and 14, have a strong locomotor activity inhibiting effect. The hexobarbital anesthesia enhancement test was performed according to the method of Nakanishi et al. [Yakushu, 90, 800 (1970)]. A group of 5 male mice were used, and after being orally treated with the compound represented by the general formula [] at various times, they were left in a thermostatic box at 26°C, and were anesthetized at each treatment time. Subthreshold amount of hexobarbital 40
mg/Kg was administered intraperitoneally. At 15 and 30 minutes after hexobarbital administration, the presence or absence of a righting reflex that lasted for 3 seconds or more was examined. If the righting reflex disappeared both times, the anesthesia enhancement rate was considered 100%, and the 50% anesthesia enhancement amount, PD ₅₀ value was calculated. As shown in Table 3, the compounds represented by the general formula [ ], such as Example Nos. 1, 5, and 14, have a strong anesthetic-enhancing effect.

[Table] The thioxanthene derivative of the present invention is formulated with commonly used pharmaceutical carriers, excipients, diluents, etc., and administered orally or parenterally in the form of tablets, capsules, granules, powders, injections, etc. Can be administered. Although the dosage varies depending on the target disease, symptoms, age, body weight, administration method, etc., it is usually administered to adults at about 1 to 50 mg once a day or once a week. The present invention will be explained in more detail below with reference to Examples. Example 1 2'-trifluoromethyl-spiro[cyclohexane-1,9'-thioxanthene]-4-one 6.5
g, N-(2-hydroxyethyl)piperazine 5.0
g. Add a catalytic amount of para-toluenesulfonic acid to a mixture of 40 ml of toluene, and remove the water produced while heating and stirring for 12 hours. After distilling off the toluene under reduced pressure, the residue was dissolved in 70 ml of methanol, and then 7.2 g of sodium borohydride was added little by little.
Reflux for a minute. After methanol is distilled off, a saturated aqueous ammonium chloride solution is added, and the mixture is extracted with ethyl acetate.
The extract is washed with saturated brine, dried over anhydrous magnesium sulfate, and then the solvent is distilled off. Thus, 4-
[4-(2-hydroxyethyl)-1-piperazinyl]-2'-trifluoromethyl-spiro[cyclohexane-1,9'-thioxanthene] is obtained. This product is a mixture of configurational isomers, and when made into a maleate salt using a conventional method, the melting point is 191℃ (decomposition).
white crystals are obtained. Isomer A was isolated by recrystallizing the base mixture several times from acetone and was obtained as white crystals with a melting point of 174-175°C. This maleate salt of the alpha isomer is a white crystal with a melting point of 199°C (decomposed). Isomer B was obtained from the acetone solution of the alpha isomer separated from the mixture of bases and was obtained as white crystals with a melting point of 161-162°C by several recrystallizations from ligroin. The maleate salt of this beta isomer has a melting point of 194°C (decomposition).
It is a white crystal. The novel 2'-trifluoromethyl-spiro(cyclohexane-1,9'-thioxanthene)-4-one used as a raw material is prepared by the following method. 52.5 g of magnesium and 4 g of magnesium are placed in 300 ml of tetrahydrofuran (THF), and the inside of the system is replaced with nitrogen gas in advance. After about 30 minutes, a solution of 174 g of chlorodimethyl ether in 300 ml of THF is added dropwise over about 2 hours. Immediately after the reaction starts -5℃~-
Cool to 10°C and maintain this temperature during addition. After completing the addition, stir for 1 hour, add 1.3 liters of THF, and add 200 ml of 2-trifluoromethylthioxanthone.
Add g in small portions as crystals over 30 minutes. -5℃
After stirring at ~-10°C for 30 minutes, stirring at room temperature for 30 minutes and then warming to 40°C. After cooling the reaction solution, it is decomposed with a saturated aqueous ammonium chloride solution in a conventional manner and extracted with ethyl acetate. After distilling off the solvent, 9-methoxymethylene-2-trifluoromethylthioxanthene (alcohol dehydrated by distillation) having a boiling point of 167° C./0.12 mmHg is obtained. Add 140 g of 9-methoxymethylene-2-trifluoromethylthioxanthene to 890 ml of 99% formic acid,
After adding 61.5 ml of 2M sulfuric acid at 70°C, stir for 2 hours and 30 minutes. After cooling, the reaction solution was poured into ice water and extracted with ethyl acetate. The extract is washed with water, dilute sodium chloride water, and water in this order, dried over anhydrous magnesium sulfate, and then the solvent is distilled off. The resulting 2-trifluoromethylthioxanthene-9-carbaldehyde is a viscous oil whose 2,4-dinitrophenylhydrazone exhibits a melting point of 194 DEG C. (decomposed). 2-trifluoromethylthioxanthene-9-
Reflux 102 g of carbaldehyde, 50 g of pyrrolidine, and 500 ml of benzene for 1 hour while removing the water produced. After washing the reaction solution with cold water and drying, benzene is distilled off to obtain pyrrolidine enamine of 2-trifluoromethylthioxanthene-9-carbaldehyde. This product contains 35g of methyl vinyl ketone and 450ml of benzene in a nitrogen stream without purification.
Heat to reflux in a tube. After 65 hours, 75 ml of acetic acid, 37.5 g of sodium acetate, and 75 ml of water were added, and the mixture was further stirred and refluxed for 4 hours. Wash the reaction solution with water and heavy sodium chloride water in that order.
After drying, add para-toluenesulfonic acid to the benzene solution.
Add 20 g of the mixture and stir while heating under reflux for 5 hours while removing the water produced. The reaction solution is washed with water, dried, and then benzene is distilled off. Treatment of the remaining oil with n-hexane-ethanol produces a
2'-trifluoromethyl-spiro(2-cyclohexane-1,9'-thioxanthene]-4-one is obtained. 2'-trifluoromethyl-spiro(2-cyclohexane-1,9'-thioxanthene) )-4-one (10 g) was dissolved in 200 ml of glacial acetic acid, 4 g of 10% palladium on carbon was added, and hydrogen gas was added to this at an internal temperature of 60°C for 12 hours.
Introduce time. After the reaction is complete, palladium on carbon is removed, water is added, the mixture is made alkaline with potassium carbonate, and extracted with benzene. The extract is washed with water, dried, and then benzene is distilled off. The residual oil is crystallized by treatment with ethanol, and the crude crystals are recrystallized from ethanol to give 2'-trifluoromethyl-spiro(cyclohexane--) with a melting point of 115-117°C.
1,9'-thioxanthene)-4-one is obtained. In addition, other novel spiro(cyclohexane-1,9'-thioxanthene)-4 used as a raw material
-one can also be prepared from a thioxanthone compound via the intermediate described below in the same manner as the raw material preparation method of Example 1. (1) Compounds where X=H, Y=H: Boiling point 191-193℃
(0.18mmHg) (2) Compound where X=C ₂ H ₅ , Y=H: boiling point 200-202
℃ (0.15mmHg) (3) Compound where X=Cl, Y=H: Boiling point 184-190℃
(0.55mmHg) (4) Compound where X=F, Y=H: Boiling point 185-190℃
(0.2mmHg) (5) Compound where X=CF ₃ , Y=F: n _D ³⁰ 1.5941 (6) Compound where X=SCH ₃ , Y=H: Boiling point 205-207
°C (0.1mmHg) (7) Compound of X=SO ₂ CH ₃ , Y=H: Melting point 131~
133℃ (8) Compound where X=SO ₂ N(CH ₃ ) ₂ , Y=H: n _D
²⁵ 1.6201 (1) Compounds where X=H, Y=H: Melting point 97-99°C (2) Compounds where X=C ₂ H ₅ , Y=H: Boiling point 180-183
℃ (0.2 to 0.35 mmHg), melting point of 2,4-dinitrophenylhydrazone 174℃ (decomposition) (3) Compound where X=Cl, Y=H: melting point 124 to 126℃ (4) X=F, Y= Compound H: Melting point 111-113°C (5) Compound where X=CF ₃ , Y=F: Melting point 2,4-dinitrophenylhydrazone 161-163°C (6) Compound where X=SCH ₃ , Y=H : Boiling point 225-227
℃ (0.55 mmHg) (7) Compound where X=SO ₂ CH ₃ , Y=H: Melting point of 2,4-dinitrophenylhydrazone 198℃ (decomposition) (8) X=SO ₂ N(CH ₃ ) ₂ , Compound of Y=H: melting point
141-143℃ (1) Compounds where X=H, Y=H: Melting point 173-175°C (2) Compounds where X=C ₂ H ₅ , Y=H: Melting point 126-127
(3) Compounds where X=Cl, Y=H: Melting point 122-124°C (4) Compounds where X=F, Y=H: Melting point 135-136°C (5) Compounds where X=CF ₃ , Y=F : Melting point 100-102°C (6) Compound of X=SCH ₃ , Y=H: Melting point 100-102
℃ (7) Compound of X=SO ₂ CH ₃ , Y=H: Melting point 158~
160℃ (8) Compound where X=SO ₂ N(CH ₃ ) ₂ , Y=H: Melting point
176-178℃ (1) Compounds where X=H, Y=H: Melting point 156-157°C (2) Compounds where X=C ₂ H ₅ , Y=H: Melting point 95-97°C (3) Compounds where X=Cl, Y=H Compound: Melting point 111-113°C (4) Compound where X=F, Y=H: Melting point 116-118°C (5) Compound where X=CF ₃ , Y=F: Melting point 145-147°C (6) X=SCH ₃ , Y=H compound: melting point of 2,4-dinitrophenylhydrazone 118 _~ 120°C (7) X= _SO2CH3 , Y=H compound: melting point 197~
199℃ (8) Compound where X=SO ₂ N(CH ₃ ) ₂ , Y=H: Melting point
150-152°C Example 2 4-chloro-2'-fluoro-spiro [2-cyclohexane-1,9'-thioxanthene] 0.9 g,
N-(2-hydroxyethyl)piperazine 0.37
g, potassium carbonate 0.39 g, potassium iodide 0.47
g, a mixture of 15 ml of dimethylformamide 65-75
Heat and stir at ℃ for 3 hours. Water is added to the reaction solution, the liberated oil is extracted with benzene, the extract is dried over anhydrous magnesium sulfate, and the solvent is distilled off. When the obtained target base is converted into a maleate salt by a conventional method, 2'-fluoro-4-[4] with a melting point of 157°C (decomposition)
-(2-hydroxyethyl)-1-piperazinyl]
-spiro[2-cyclohexene-1,9'-thioxanthene], dimaleate is obtained. The novel 4-chloro-2'-fluoro-spiro[2-cyclohexane-1,9'-thioxanthene] used as a raw material is prepared by the following method. 2'-Fluoro-spiro[2-cyclohexene-
20 g of 1,9'-thioxanthene]-4-one is suspended in 250 ml of ethanol, 2.6 g of sodium borohydride is added, and the mixture is stirred at room temperature for 1 hour. After the reaction is completed, ethanol is distilled off. The residue is decomposed by adding water and extracted with chloroform. After washing the extract with water and drying, chloroform is distilled off to obtain 2'-fluoro-spiro(2-cyclohexene-1,9'-
Thioxanthene]-4-ol is obtained as a viscous oil. This product can be used in the next reaction without purification. TLC (benzene): Rf = 0.1 Add 6.3 g of phosphorus pentachloride to 50 ml of benzene, and add 8.9 g of 2'-fluoro-spiro[2-cyclohexene-1,9'-thioxanthene]-4-ol to 50 ml of benzene under cooling. Drop the solution. After stirring at room temperature for 1 hour, the reaction mixture was poured into ice water and extracted with ethyl acetate. After washing the extract with water and drying, ethyl acetate was distilled off, and 4-chloro-2'-fluoro-spiro[2-cyclohexene-1,9'-thioxanthene] with Rf = 0.8 was found to be viscous by TLC (benzene). Obtained as a viscous oil. For example, the following thioxanthene derivatives are produced in the same manner as in the above examples. 3) 4-[4-(2-hydroxyethyl)piperidino]-2'-trifluoromethyl-spiro[cyclohexane-1,9'-thioxanthene], 1/2
Melting point of fumarate 240℃ (decomposition) 4) 4-[4-(3-hydroxypropyl)-1
-piperazinyl]-2'-trifluoromethyl-spiro[cyclohexane-1,9'-thioxanthene], dimaleate, hemihydrate, melting point 183℃
(Decomposition) 5) 4-[4-{2-(2-oxo-3-oxazolidinyl)ethyl}-1-piperazinyl]-2'-
Trifluoromethyl-spiro [cyclohexane-
1,9'-thioxanthene], 2 maleate salt melting point 185℃ (decomposition) 6) 4-[4-{2-(3-methyl-2-oxo-1-imidazolidinyl)ethyl}-1-piperazinyl] -2'-trifluoromethyl-spiro[cyclohexane-1,9'-thioxanthene] 7) 4-[4-(2-hydroxyethyl)-1-
piperazinyl]-spiro[cyclohexane-1,
9′-thioxanthene], 2 maleate 1/2
Melting point of hydrate 167-169℃ 8) 2'-Ethyl-4-[4-(2-hydroxyethyl)-1-piperazinyl]-spiro[cyclohexane-1,9'.thioxanthene], dihydrochloride. 1/
Melting point of tetrahydrate: 279°C (decomposition) 9) 2'-Ethyl-4-[4-(2-hydroxyethyl)piperidino]-spiro[cyclohexane-
1,9'-thioxanthene], melting point 181-184°C 10) 2'-chloro-4-[4-(2-hydroxyethyl)-1-piperazinyl]-spiro[cyclohexane-1,9'-thioxanthene] , dimaleate quarter hydrate melting point 177℃ (decomposition) 11) 2'-chloro-4-[4-(2-hydroxyethyl)piperidino]-spiro[cyclohexane-
1,9'.thioxanthene], 1/2 fumarate melting point 256℃ (decomposition) 12) 2'-Fluoro-4-[4-(2-hydroxyethyl)-1-piperazinyl]-spiro[cyclohexane- 1,9'-thioxanthene], 2 maleate salt melting point 153℃ (decomposition) 13) 2'-Fluoro-4-[4-(2-hydroxyethyl)piperidino]-spiro[cyclohexane-1,9'- Thioxanthene], 1/2 fumarate melting point 250℃ (decomposition) 14) 6'-Fluoro-4-[4-(2-hydroxyethyl)-1-piperazinyl]-2'-trifluoromethyl-spiro[ Melting point of cyclohexane-1,9'-thioxanthene], dimaleate 187℃ (decomposition) 15) 6'-Fluoro-4-[4-(2-hydroxyethyl)piperidino]-2'-trifluoromethyl- Spiro[cyclohexane-1,9'-thioxanthene], 1/2 fumarate salt melting point 244℃ (decomposition) 16) 4-[4-(2-hydroxyethyl)-1-
piperazinyl]-2'-methylthio-spiro[cyclohexane-1,9'-thioxanthene], 2 maleate salt melting point 182°C (decomposition) 17) 4-[4-(2-hydroxyethyl)-1-
Piperazinyl]-2'-methylsulfonyl-spiro[cyclohexane-1,9'-thioxanthene], 2
Melting point of maleate salt 154~156℃ 18) 4-[4-(2-hydroxyethyl)piperidino]-2'-methylsulfonyl-spiro[cyclohexane-1,9'-thioxanthene], melting point 216~
218℃ 19) 2'-dimethylsulfamoyl-4-[4-
(2-hydroxyethyl)-1-piperazinyl]-
Spiro [cyclohexane-1,9'-thioxanthene], dimaleate, hemihydrate, melting point 186℃
(Decomposition) 20) 2'-chloro-4-[4-(2-hydroxyethyl)-1-piperazinyl]spiro[2-cyclohexene-1,9'-thioxanthene], 2-maleate, melting point 163℃ ( Disassembly)

Claims (1)

[Claims] 1. General formula A thioxanthene derivative represented by and its salt. [In the above formula, X is hydrogen, lower alkyl, halogen, trifluoromethyl, -SR ¹ , SO ₂ R ¹ , -SO ₂ N
(R ¹ ) ₂ (where R ¹ represents lower alkyl), Y
is hydrogen or fluorine, Z is N- or CH-, L is a group -OH,
[Formula] [Formula] (where R ² represents lower alkyl), and n represents 2 or 3. The dotted line in ring A indicates that this moiety may form a double bond. However, when Y is fluorine, X represents trifluoromethyl. ]