JPS61197575A - Novel 4h-1-benzopyran-4-ones and sulfur-containing analoguesthereof - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides novel compounds, synthetic methods, pharmaceutical compositions and uses of the compounds, particularly as antipsychotic agents.

Numerous examples of aminoalkoxy benzobyranones are known. For example, US Pat. No. 4,428,955 discloses compounds of general formula m for the treatment of allergies. For example, compounds such as those of formula (1) as generally shown in U.S. Pat. No. 4,520,128 are for use as antihypertensive agents; 8
No. 54 discloses compounds of formula V that have use as vasodilators. however,
None of the aminoalkoxybenzopyranones described in the above US patent specifications suggests any combination of structural changes in the compounds of the present invention described below. In particular, use as antipsychotic agents for the compounds disclosed above is not mentioned in the teachings of these patents. Mokukuni Patent Application No. 65
1.972 specifies benzopyran-2 for antipsychotic use.
-on classes are disclosed. The present invention comprising benzopyran-4-one derivatives is not suggested by such previously disclosed compounds.

The present invention is based on the following formula (1) wherein X is oxygen or sulfur and R is or (Ar in the formula) phenyl &b) lower alkyl, lower alkoxy, lower thioalkoxy, halogen or trifluoromethyl; substituted phenyl or c)H
θt (where Hat is 2-pyridinyl%3-pyridinyl or 4-pyridinyl, or the above 2 polysubstituted with lower alkyl, lower alkoxy or halogen)
-23- or 4-pyridinyl, 2-pyrimidinyl,
4-pyrimidinyl or 5-pyrimidinyl,
or the above 4- or 5-pyrimidinyl polysubstituted with lower alkyl, lower alkoxy or halogen;
2-pyrazinyl or polysubstituted with % or lower alkyl, lower alkoxy or halogen;
shell.

Is it 2-chenyl or 6-chenyl?

or the above 2- or 5-chenyl, 2-7-ranyl or 3-furanyl polysubstituted with lower alkyl or halogen, or the above 2- or 6-furanyl polysubstituted with lower alkyl or halogen% 2-thiazolyl or 5-thiazolyl, or the above 2- or 5-thiazolyl polysubstituted with lower alkyl or halogen) and =
is a single or double bond) and -0-(
OH2h-5-R is present at the 5,6,7 or 8 position of the fused ring system] or a pharmacologically acceptable acid addition salt thereof.

The novel compounds of formula I are numbered counterclockwise starting from Can be attached. Because of the carbonyl group in the 4-position, these compounds are called benzopyran-4-ones when X is oxygen and benzothiopyran-4-ones when X is sulfur.

Furthermore, as shown in the following Reaction Formula I Reaction Formula (■), the present invention can be used to convert a compound of the formula (1) (wherein Hal is ). or B has the above definition) consisting of reacting with an amine having the above definition! The present invention relates to a method for producing a compound.

The method of the present invention can also be carried out by preparing a compound of formula (1) with anhydrous 1-promo-5-/-lopropane or other appropriately substituted alkane in the presence of 2co5 as shown in the following reaction formula (1) or (2). It also relates to a method for producing a compound of formula (1), which comprises reacting with.

A compound of formula (2) can be prepared in a similar manner starting from a compound of formula (2).

On the other hand, 1) the method of the present invention is as shown in the following reaction formula (1) Reaction formula (2): 1) 2,6-hydroxyacetophenone, 1-i spider-3-chloropronone or an appropriately substituted alkane; Reacting potassium carbonate to obtain a compound of formula (1), then 2) treating the product of step 1 above with sodium metal and ethyl formate and finally 3)
The product of step 2 was treated with HOjl in ethanol to obtain 2M
5.

The present invention also provides a compound of formula I having the above definition, or a pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable carrier, which is useful for the treatment of psychosis, such as schizophrenia. It is a pharmaceutical composition that

Furthermore, the present invention is a method for treating psychosis, which comprises administering an effective amount of the compound of formula (1) or a confectionery-acceptable salt thereof to a human exhibiting psychotic symptoms.

Antipsychotic effects are measured by standard laboratory means.

The compounds shown in Section 1 are active in laboratory tests that are useful as predictive tests for antipsychotic efficacy (eg, treatment of schizophrenia). Some of these tests include J, R,
Pharmacol Bioch by McLean et al.
Em, Behav, 197 B (8197), which screens for compounds that reduce locomotor activity in mice and rats without causing ataxia. Inhibition (
ff1D5θ for Inh, Loc, Act, ) ((mouse, intraperitoneal administration) and (rat, oral administration))
Shows dosage. All known antipsychotics are active in this test. Compounds according to the inventors are also active at doses as low as 0.35 μ/l.

Further studies of these compounds indicate that their mechanism of action involves selective activation of presynaraptic do94min receptors in the animal brain. i.e., they are 10-6 to 10''7 in vitro, as measured by inhibition of (3H)haloperidol binding.
Showing affinity for dopamine receptors in the molar range (D
, MolPharmacol by R. Burt et al.
, 1976 (12) 800). Another proof of how this effect appears is, for example, α−
Decreased prolactin release in rats treated with methyl-para-tyrosine, where X is oxygen and -o-(CH2
) observed when treating with a compound of formula I in which 3-R is sb in the 7-position of the fused ring system and R is 4-(phenyl)pi is radionyl) (A, G, Trantz) Prog.

Brain, Res, 1975 (39) 311
Please refer to ).

Inhibition of dopamine synthesis in rats treated with gamma-butyrolactone (GBL), where X is oxygen, -0
-(CH2)! Compounds of formula I are used in which l-R is in the 7-position and R is 4-(phenyl)-1,2,5,6-titrahydropyridinyl or 4-(phenyl)py is radicalinyl. (observed during treatment) (J, R, W
Naunyn-8chmied by Mr. alters et al.
eberg's Arch, Pharmacol, ,
1976 (296) 5) and in single single recording experiments where X is oxygen, -o-(ca
2) The dopamine neuron observed during treatment with a compound of formula (3) in which 3-R is in the 7-position and R is 4-(phenyl)pyOradinyl: / excitation If (f
'iringrate) inhibition (L, R, 5kir'b
o11. 5science 1979 (20
6) 80) t-can be mentioned. Because of this mechanism of action, these compounds appear to have little or no tendency to produce the extrapyramidal side effects observed with traditional neuroleptic drugs.

That is, the present invention provides an anti-N psychosis agent, such as for the treatment of schizophrenia, which has a low probability of side effects.

Analogs of the compound of formula (1) are prepared and the McLe
It was found to be inactive in a test by An et al. For example, an aminoalkoxybenzopyranone containing a dialkylaminopropoxy side chain is used as a vasodilator with the above-mentioned structural formula (1) (described in U.S. Pat. No. 3,098,854).
It was manufactured as an example of the mold. Similarly, aminoalkoxy produced nzobiranones as an example of the structural formula (2) claimed by Boehringer (US Pat. No. 4,428,955) for use in the treatment of allergies.

In both cases the structural characteristics of these compounds make them unsuitable for the desired dopamine receptor.

These compounds are active in animal studies predicting neuroleptic effects for the treatment of patients exhibiting symptoms of psychosis, such as schizophrenia. Regardless of the route of administration chosen, the compounds of the present invention are formulated into package-acceptable dosage forms by conventional means known in the pharmaceutical art.

However, the generally preferred method of administration is by oral dosage form.

These compounds may be administered in unit oral dosage forms such as tablets, capsules, tapes, powders or %M. They can also be administered rectally or vaginally in the form of herbal medicines or puji, for example. Furthermore, they can be introduced parenterally (eg subcutaneously, intravenously or intramuscularly) using forms known to those skilled in the art.

A therapeutically effective but nontoxic amount of a compound of Formula 1 or a salt thereof is employed.

The dosage range for the treatment of psychosis with the compounds of this invention is selected according to a variety of factors, including the patient's body type, age, severity, sex, and medical conditions, the degree of psychosis, the route of administration, and the particular compound used. Determination of the appropriate dosage for a particular condition will be apparent to those skilled in the art. Generally, treatment is initiated with smaller doses that are less than the optimal dose of the compound. Thereafter, the dosage is increased little by little under constant conditions until the optimal effect is achieved. 1.
The total daily dose may be administered in portions during the day if desired.

The initial dose of the compound of the present invention is usually 1 /
from d to at least 100 towns/halls, preferably from 1 to 50 g9
/# Administered orally. Each dose is administered 1 to 4 times per day or as needed. If other forms of administration are used, similar dosages will be administered.

The compounds of the present invention may also contain pharmacologically acceptable acid addition salts such as hydrochloride, hydrobromide, hydroiodide, sulfate, etc.
Phosphate, Acetate, Propionate, Lactate, Maleate, Sinate, Succinate, Tartrate, Cyclohexanesulfamate, Methanesulfonate, Ethanesulfonate, Hensensulfone! 11m, ) may also be administered as luenesulfonate, etc. Additionally, the compounds of the invention may be administered in appropriate hydrated or solvated forms.

Table 1 below is the formula! and their activity for the above-mentioned uses.

Table 1 4H-1-bennovine 1 of formula I with antipsychotic activity
0 -(C)I2)5- 7 4-phenyl-
1,2,3,6-025H25NOS Tetrahydro-1
-Pyridinyl 20 -(OH2)5- 7 4-7E-rubyradyl C22H24N205(I20)-4-ones 1348-155.5 0,7
29.5149~152 2A
43160～163 1t1
1B, 6255-257 112
13.2>'275 7.7
as195~195 7.7
>50182-184 14J1
>502450-244,5250 210-212 5A 4J
3211-215 41 4H-1-Benzozylene O of formula I with uneven antipsychotic activity
-(CH2)・′″72″:, 72″:, Dougata11・“
・Horse 0.150''' (OH2) 5-7 4-, <.4
″″l ) *′7″″) 0丑・6N2°4°-hiherazinyl 18. 0 -(OH2)5- 5 4-(phenyl)biba2dinyl 022H24Nf0519 0
-(OH2)i-64-Cphenyl)pyradi5yl025H26N20S '2E publication (I20) 21 O-(OHz)s-75,,42-glimidik) 'A 0f5HA2Na05''NA means unavailable.

No 4-on class 229-230 7 7.1267-
269 5-6 1.7201-203
>30 NA”・25B-2
5914-1517, 8230-255 50
>30240~245 >30
NA umbrella 258rJ~25B5 3
7.5106-112153 15.619
3~195 5 t5204~20
6 0.35 t9124~1292
57>30 Certain compounds within the range of 2) are preferred because they have more advantageous pharmacological effects.

That is, 10-(nod 2) 2 in the 6- or 7-position of the ring system.
Compounds of formula I with -5-R are preferred. More preferably, -0-(OH2)2-5-R in the formula is -o-(cH2
)3-p or -o-(cH2)4-R and set A
Compounds of formula I, wherein r is unsubstituted.

The most preferred examples include 7-(3-(4-phenyl-1,2,5,6-tetrahydro-1-pyridyl)propoxy)-4H-1-benzopyran-4-one,
7-(3-(4-phenylhyherazinyl)propoxy)
-4H-1- is ndzopyran-4-one, 7-(3-(4
-(2-pyridylpiperazinyl)propoxy)-4H-
1-benzopyran-4-one % 6-C4-(4-phenyl-1-piperazinyl)butoxycou 4H-1-benzopyran-4-one and 7-(4-(4-722-1-bi is furanyl) butoxy)-4H-1-benzopyran-4-one.

Examples of -(CH2)-2-s are ethylene, propy7lene, butylene and dungtylene.

Ar used in the description of the invention is a) phenyl, b) e.g.
t Ha01-6 phenyl substituted with 1 to 3 substituents such as furkyl 5C1-6 alkoxy, orogen, or c) Het (however, whether Het is 2-pyridinyl, 6-pyridinyl or 4-pyridinyl) or C1-
the above 2-95- or 4-pyridinyl substituted with 6 alkyl% C1-6 alkoximosy or halogen;
the above 2-9 which is 2-pyrimidinyl, 4-pyrimidinyl or 5-pyrimidinyl or substituted by C1-6 alkyl, 01-6 alkoxy or halogen;
4- or 5-piIJ Midinyl % 2-pyrazinyl or substituted by 01-6alkyl101-6alkoxymohalogen, 2-pyrazinyl, 2-pyrazinyl;
-chenyl or 3-chenyl or C1-
The above 2- substituted with 6 alkyl or halogen
or 6-chenyl, 2-7ranyl or 6-furanyl or substituted by cl-6 alkyl or halogen, 2- or 3-furanyl, 2-
Thiazolyl or 5-thiazolyl or still cl
2 above substituted with -6 alkyl or halogen
- or 5-thiazolyl).

C1-6 alkyl is methyl, ethyl, propyl.

Butyl means butyl, hexyl and its isomers.

C1-6 alkoxy means methoxy, ethoxy, propoxy, butoxy, butoxy, hexoxy and isomers thereof.

As examples of halogen, mention may be made in particular of chloro, fluoro, trifluoromethyl or bromo.

In general, compounds of formula (1) are compounds of formula (1) having the above definitions, such as (5-chloropropoxy)-4H-benzopyran-4-one (produced by the method set forth in Example 1 below), having the above definitions. An approximately equimolar mixture of the appropriate compound of formula HA or oil is dissolved in dimethylformamide (D) in the presence of NaHCO3 and catalyst NaI.
MF'), acetonitrile, ethanol, or the like at a temperature of 50 to 120°C, preferably 85 to 90°C. Separation and purification are accomplished by conventional methods; for example, the free base is purified in some cases by recrystallizing the crude product from ethyl acetate.

The intermediate of formula (1) is generally synthesized using 7-hydroxy-4 in the presence of an anhydrous alkali metal carbonate in a solvent such as acetone, as shown in the above reaction formula (2).
This is accomplished by contacting H-1-benzopyran-4-one with a suitably substituted alkane such as 1-promo-3-chloropropane under reflux conditions for 2 to 24 hours, preferably 10 to 12 hours. The intermediate of formula (2) is produced in the same manner.

The intermediate of formula (3) is generally converted into 2,6-
Cyhydroxyacetophenone is prepared from a mixture of suitably substituted alkanes such as 1-promo-3-chloropropane.

Again, as in the case of producing the compound of formula (1) above, the above mixture is heated in a solvent such as acetone for 2 hours to
Reflux for several days, preferably about 60 hours. The crude product obtained from this reflux is further treated with sodium chloride in ethyl acid, also under reflux conditions, for 60 minutes to 4 hours, preferably about 1 hour. In this way, a compound of formula (5) can be obtained.

In each case 1, conventional methods of separation and purification are used.

The starting materials required for the process according to the invention are either commercially available or can be synthesized by methods known in the art of organic chemistry. For example, 6-hydroxy-
4H-1-benzopyran-4-one or 7-hydroxy-4H-1-benzopyran-4-one is (), N, and rafeenk.

[Chem, Heterocyclic Compounds (
C%am, Heterocyclic Compound
ds)j, 1972(8)935.

The preparation of compounds of formula l in which X is sulfur is analogously prepared by methods obvious to those skilled in the art from starting materials that are commercially available or synthesized by methods known to those skilled in the art. .

Acid addition salts of compounds of formula I are prepared by reacting the compound with stoichiometric equivalents of an acid corresponding to a legally acceptable acid addition salt, e.g. sulfate, phosphate, or methanesulfonate. It is manufactured by making. However, other suitable pharmaceutically acceptable salts within the scope of this invention include acid salts such as hydrochloric acid and sulfamic acid and organic acids such as ethanesulfonic acid, benzenesulfonic acid sp-
These are derived from fluorine sulfonic acid, etc., and give hydrochloride, sulfamate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, etc., respectively. .

Production methods and examples are described below to better explain the present invention, but the present invention is not limited thereto.

Preparation method 1 7-(3-chloropropoxy)-4H-1-benzopyran-4-one 7-hydroxy-4H-1- in 10100O acetone
Benzopyran-4-one, ■ (40,5jl; 0.25
Mo/l/; G, N, Dorafeenko et al. [Chem.

Heterocyclic compounds (Chem.

Heterocyclic Compounds) Mountain 1
(manufactured by the method described in 972(8)935)
, 1-promo 3-chloropropane! (78, 59,
0.50 mol) and anhydrous potassium carbonate (499.0,
50 mol) was heated under reflux for 16 hours. The mixture was filtered through Celite and concentrated in vacuo. The remaining dark red oil was triturated with ether to give 57.89C9.
The title compound of 7th) was obtained. Melting point 72-73°C.

Example 1 7-(3-(4-('2-chlorophenyl)-1-
Pyrradinyl)propoxy)-4H-1-benzopyran-4-one The following procedure is a typical example of the preparation of benzopyran-4-one represented by the general formula (2) in which X is oxygen.

7-(3-chloropropoxy)-4H-benzopyran-4-,one-(2,3851,10 mmol) prepared by the above Preparation Method 1 in dimethylformamide,
1-(2-chlorophenyl)pi is radine dihydrochloride (2,
96jl, 11 mmol), sodium bicarbonate (
59 & 35 mmol), sodium iodide (D, 1jl
, 0.6 mmol) was mechanically stirred and heated at 85-90 °C for 7 h. The solvent was then evaporated in vacuo and the residue partitioned between water and dichloromethane. The organic phase was treated with an excess of 10% HOfi solution in methanol, evaporated in vacuo and the residue recrystallized from ethanol/ethyl acetate to give 6.22 7-(3-
(4-(2-chlorophenyl)-1-hihalazinyl)propoxy, l-4H-,1-benzopyran-4-one was obtained as its hydrochloride.

Melting point 201-203°C (decomposition).

All other 7-(3-abanoproboxy)-4H-1-benzopyran-4-ones listed in Table 1 were prepared by this procedure. In some cases the free base was purified by recrystallizing the crude product from ethyl acetate.

Example 2 7-(3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propoxy)-4H-1-benzopyran-4-one The title compound was converted to its hydrochloric acid by the same procedure as above. Manufactured as salt. Melting point 128-162°C (decomposition).

Example 6 7-(5-(4-phenyl-1-pilysinyl)propoxy)-4H-1-benzopyran-4-one The title compound was prepared as its hydrochloride by the same procedure as above. Melting point: 182-184°C.

Further examples of the 4H-1-benzopyran-4-ones prepared include, for example, the 5-substituted to 6-Wt-substituted analogues included in the compounds of formula I, in which X is oxygen, as well as the above-mentioned Example 1. Examples include products in which the trimethylene chain of the compound described in 1 is replaced by a tetramethylene chain.

Such compounds are further illustrated in coating 1 above.

Production method 2 7-(4-chlorobutoxy)-4H-1-benzopyran-4-one The title compound, melting point 75-78°C, is 1-bromo-4-chlorobutane and 7-hydroxy-4H-1-benzopyran-4-one. Starting from 7-(3-chloropropoxy)-4H-,1-benzopyran-4-one was prepared as described above.

Example 4 7-(4-(4-phenyl-1-piradinyl)butoxy)-4H-1-benzopyran-4-one The title compound was prepared by the method described in Examples 1 to 3 above. . That is, 7-(4-chlorobutoxy)-4H-1-benzopyran-4-one (
3,799,15 mmol) is usually added to 1-
Phenylpi was treated with radin (2,599,16 mmol) to give 5.769 7-(4-(4-phenyl-1-biverazinyl)'butoxy)-, an-1--<nzopyran-4-, t7 - Obtained 1.5 Hen (H2O). Melting point 204-206°C.

Production method 6 6-(4-chlorobutoxy)-4H-1-benzopyran-4-one The title compound, melting point 75-77°C, is 1-promo-4-chlorobutane and 6-hydroxy-4H-1-benzopyran-4-one ( The aforementioned Dorofeenk.

(obtained using the method of
(3-chloropropoxy)-4H-1-penzopyran-
It was produced by the same procedure as described for 4-one.

Example 5 6-(4-(4-phenyl-1-piperazinyl)butoxy)-4H-1-benzopyran-4-one The title compound is prepared by the method described above for compounds of formula I, where X is oxygen. It was done.

That is, 6-(4-chlorobutoxy)-4H-1-benzopyran-4-one (3,79
jI, 15 mmol) was reacted with 1-phenylpiperazine (2,59F% 16 mmol) in the usual manner to give 3.52 6-(4-(4-phenyl-1-
(radinyl)butoxy]-aH-1--<nzopyran-4-one was obtained as its dihydrochloride. Melting point 193-1
95℃. (Please refer to the reaction formula ■ above) Production method 4 5-(3-chloropropoxy)-4H-1-benzopyran-4-one 2.6-dihydroxyacetophenone (209°13
1 mmIJ mol), 1-/Cumo-6-chloropropane (3
1,48 jl, 200 mmol) and potassium carbonate (
14,79,150 mmol) were refluxed in 500 ml acetone for 60 hours. The mixture was then filtered t-W and evaporated in vacuo to give 28jl of crude 2-1-chloropropoxy)-6-hydroxyacetophenone, which was used directly without further purification.

2-(3-chloropropoxy)-6-hydroxyacetophenone, K (28F, 120 mmol) at 1001n
Sodium metal (10,99
, 474 mmol) and refluxed for 1 hour. The mixture was then poured onto ice, the yellow solid formed was filtered, dried and immediately diluted with 2 ml in 200!lfi ethanol @ HOJ! It also refluxed. After cooling, the acid was neutralized with anhydrous potassium carbonate, and the solution was filtered and concentrated. Upon cooling in the freezer, the residual red oil became a straight solid, mp 50-56 DEG C., which was identified as the title compound (see Scheme 1 above).

Example 6 5-(3-(4-phenyl-1-pyrodinyl)propoxy)-4H-1-banzopyran-4-one The title compound was prepared by the method described in Examples 1 to 5 above. It was done. In this case the free base was isolated. melting point 10
6-112℃.

Patent applicant: Warner-Lambert Kompany et al.
given name

Claims (1)

[Claims] 1) The following formula ▲ There is a mathematical formula, chemical formula, table, etc. ▼ I [In the formula, X is oxygen or sulfur, and R is ▲ There is a mathematical formula, chemical formula, table, etc. ▼ A or ▲ Numerical formula, Chemical formulas, tables, etc. are available▼B (In the formula, Ar is a) phenyl, b) phenyl substituted with lower alkyl, lower alkoxy, lower thioalkoxy, halogen or trifluoromethyl, or c) H
et (provided that Het is 2-pyridinyl, 5-pyridinyl or 4-pyridinyl, or the above 2 substituted by lower alkyl, lower alkoxy or halogen)
-, 3- or 4-pyridinyl, 2-pyrimidinyl,
4-pyrimidinyl or 5-pyrimidinyl,
or the above 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl substituted with lower alkyl, lower alkoxy or halogen, or lower alkyl,
2- substituted by lower alkoxy or halogen
2- or 6-thienyl, 2-furanyl or 3-thienyl, pyrazinyl, 2-thienyl or 3-thienyl or substituted by lower alkyl or halogen
-furanyl or 2- or 3-furanyl, 2-thiazolyl or 5-thiazolyl substituted by lower alkyl or halogen, or 2- or 5-thiazolyl substituted by lower alkyl or halogen) and ■ is a single bond or a double bond) and -O-(CH_2)_2_-_5-R is present at the 5, 6, 7 or 8 position of the fused ring system] or its Pharmacologically acceptable acid addition salts. 2) The compound according to claim 1, wherein X is oxygen. 3) A compound according to claim 1, wherein X is sulfur. 4) The compound according to claim 2, wherein the substituent -O-(CH_2)_2_-_5-R is present at the 6-position of the fused ring system. 5) A compound according to claim 2, wherein the substituent -O(CH_2)_2_-_5-R is present at the 7-position of the fused ring system. 6) -O-(CH_2)_2_-_5-R is -O(CH
The compound according to claim 2, which is _2)_3-R or -O(CH_2)_4-R. 7) Specific embodiments include 7-[3-(4-phenyl-1,
The compound according to claim 5, which is 2,3,6-tetrahydro-1-pyridyl)propoxy]-4H-1-benzopyran-4-one. 8) A specific embodiment is 7-[3-(4-phenylpiperazinyl)propoxy]-4H-1-benzopyran-4-
6. The compound according to claim 5, which is 1 or a hydrate thereof. 9) A specific embodiment according to claim 5, wherein the specific embodiment is 7-[3-(4-(2-pyridyl)piperazinyl)propoxy]-4H-1-benzopyran-4-one or its hydrochloride. Compound. 10) A specific embodiment is 6-[4-(4-phenylpiperazinyl)butoxy]-4H-1-benzopyran-4-
5. The compound according to claim 4, which is 1 or a hydrochloride thereof. 11) A specific embodiment is 7-[4-(4-phenylpiperazinyl)butoxy]-4H-1-benzopyran-4-
6. The compound according to claim 5, which is 1 or a hydrochloride thereof. 12) Claim 5, wherein the specific embodiment is 7-[5-(4-(3-chlorophenylpiperazinyl)propoxy]-4H-1-benzopyran-4-one or its hydrochloride) 13) Specific embodiments include 7-[3-(4-(2-methoxyphenyl)piperazinyl)propoxy]-4H-1-
The compound according to claim 5, which is benzopyran-4-one or its hydrochloride. 14) The specific embodiment is 7-[3-(4-(2-methylphenyl)piperazinyl)propoxy]-4H-1-benzopyran-4-one or its hydrochloride, according to claim 5. Compound. 15) The specific embodiment is 7-[3-(4-(3-methylphenyl)piperazinyl)propoxy]-4H-1-benzopyran-4-one or its hydrochloride, according to claim 5. Compound. 16) The specific embodiment is 7-[3-(4-(4-methylphenyl)piperazinyl)propoxy]-4H-1-benzopyran-4-one or its hydrochloride, according to claim 5. Compound. 17) A specific embodiment is 7-[3-(4-(4-fluorophenyl)piperazinyl)propoxy]-4H-1-
The compound according to claim 5, which is benzopyran-4-one or its hydrochloride. 18) A specific embodiment is 7-[3-(4-(3,4-dimethylphenyl)piperazinyl)propoxy]-4H-
The compound according to claim 5, which is 1-benzopyran-4-one or its hydrochloride. 19) A specific embodiment is 7-[3-(2-pyrimidylpiperazinyl)propoxy]-4H-1-benzopyran-
A compound according to claim 5 which is 4-one or a pharmaceutically acceptable salt thereof. 20) Specific embodiments include 7-[3-(4-(4-chlorophenyl)piperazinyl)propoxy]-4H-1-benzopyran-4-one or a hydrate thereof, 7-[3-(
4-phenylpiperidinyl)propoxy]-4H-1-
Benzopyran-4-one or its hydrochloride, 7-[3-
(4-(2-chlorophenyl)piperazinyl)propoxy]-4H-1-benzopyran-4-one or its hydrochloride, 7-[3-(4-(3,4-dichlorophenyl)
piperazinyl)propoxy]-4H-1-benzopyran-4-one or its hydrochloride, 7-[3-(4-(4-
methoxyphenyl)piperazinyl)propoxy]-4H
-1-benzopyran-4-one or its hydrochloride, 7-
[3-(4-(3-hydroxyphenyl)piperazinyl)propoxy]-4H-1-benzopyran-4-one or its hydrochloride or 5-[3-(4-phenylpiperazinyl)propoxy]-4H -1-benzopyran-4
7. The compound according to claim 6, which is -one. 21) A pharmaceutical composition containing an antipsychotically effective amount of a compound according to claim 1, together with a pharmaceutically acceptable carrier. 22) A method of treating psychosis, comprising administering to a psychosis patient an effective amount of a compound according to claim 1 in a unit dosage form. 23) A method according to claim 22, wherein the psychosis is in particular schizophrenia.