CN1844120A - Aryl piperazine modified benzo [b] thiophene compounds and their preparation method and use - Google Patents
Aryl piperazine modified benzo [b] thiophene compounds and their preparation method and use Download PDFInfo
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- CN1844120A CN1844120A CN 200610013548 CN200610013548A CN1844120A CN 1844120 A CN1844120 A CN 1844120A CN 200610013548 CN200610013548 CN 200610013548 CN 200610013548 A CN200610013548 A CN 200610013548A CN 1844120 A CN1844120 A CN 1844120A
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- piperazine
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- propyl alcohol
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Abstract
This invention belongin to medicinal chemistry, pubilize the structure and synthesis of aryl-diethylenediamine modified benzo[b]thiophenes with antidepressant function. Its structure is depicted as picuture. Ar structure is as depicted.the synthesis of the compound is as followings: mix 1M 3-propionyl benzo[b]thiophenes,1-5M cavaform and 1-5M aryl-piperazidine hydrochlorate in 1-50 weight folds ethanol, inverse flowing react 1-80 hours, obtain 1-( benzo[b]thiophenes-3)-2- methyl-3-( 4-aryl-piperazidine-)1- acetone; Mix 1M 1-( benzo[b]thiophenes-3)-2- methyl-3-( 4-aryl-piperazidine-)1- acetone and 0.2-5M sodium borohydride in 1-50 weight folds of ethanol, react at 0-100deg C for 1-20, 1-( benzo[b]thiophenes-3)-2- methyl-3-( 4-aryl-piperazidine-)1- propanol obtained. This kind of compounds could be used for antidepressant drug preparation in the form of free alkali or salt. This invention is advantageous in simplied preparation and easy manipulation.
Description
Technical field
The present invention relates to structure of a kind of aryl piperazine modified benzo [b] thiophene compound with antidepressant activity and its production and application, belong to the pharmaceutical chemistry field.
Background technology
Dysthymia disorders is a kind of common mental disorder, belong to affective disorder, along with rhythm of life is constantly accelerated, people's stress also increases gradually, and dysthymia disorders has become the common disease of modern society, high morbidity, and its sickness rate is soaring fast: according to incompletely statistics, whole world patients with depression has accounted for the 3%-5% of world population at present, almost see each age level, its morbidity is about 3% in the general population, in the patient population of general hospital polyclinic's health care service about about 10%; And in patient's (as cardiovascular diseases, diabetes) of chronic physical disease, that suffers from depressive disorder can but, have only the patient of considerably less ratio identified up to 20%.By pharmacological agent, wherein about 2/3 patient can obtain different curative effects, as the end in time discern and treat they will bring more serious consequence (as commit suiside, disabled, too much medical resource waste etc.).The World Health Organization predicts the year two thousand twenty, and dysthymia disorders will become the 2nd big cause that causes deformity.
Nineteen fifty is for tricyclic antidepressant (TCA having occurred, Anticholinergic), 5-HT selectivity reuptake inhibitor class SSRI (Fluoxetine has appearred in the 1980's, Paroxetine, Sertaline, Citalopram, Fluvoxamine) because of its good antidepressant performance, replace TCA gradually and become leading product on the thymoleptic market, yet owing to the SSRI indirect action has nauseating in all 5-HT acceptors, anxiety, insomnia, sexual function side effect such as decrease, and maximum weakness is a lag-effect in clinical use, promptly generally after week antidepressant effect could appear at the 2-6 that begins to take medicine, therefore in order to seek safety, quick acting, the thymoleptic that side effect is little, the medicine scholars have carried out various trials.
The thymoleptic such as the NE/5-HT reuptake inhibitor SNRI (Venlaxine of some new role mechanism appearred in generation nineteen ninety so far, Milnacipran, Duloxetine, Nefazodone), selectivity oxidase inhibitor MAOI (Moclobemide, Toloxatone), selective N E reuptake inhibitor NARI (Reboxetine), NE energy and specificity 5-HT energy antidepressive NaSSa (Mirtazapine), though these medicines are compared with the SSRI class, on curative effect and quick acting, be improved, but lag-phase in 1-2 week is still arranged, therefore very urgent to the drug research of quick acting more.
Reported first such as Artigas were with pindolol (blended 5-HT in 1993
1A/ beta-2 adrenoceptor antagonist) can significantly reduce lag-phase of SSRIS with the medication of SSRIS antidepressant medicament combination, strengthen antidepressant effect, patient symptom is significantly improved.Result of study subsequently shows, 5-HT
1AAntagonist WAY100635 and several SSRIS connection and medication also can show this effect.A kind of hypothesis of this phenomenon is thought it may is the 5-HT of preceding nerve synapse
1ATherefore the autonomous acceptor of nerve synapse 5-HT before the antagonistic action of autonomous acceptor can be blocked has increased the 5-HT concentration between the nerve synapse gap, thereby improves curative effect, reduces the lag-phase etc.
On this basis, present research focus mainly is with various 5-HT
1AThe primary structure of receptor antagonist or agonist primary structure and SSRIS is combined in the molecule and makes it 5-HT conducting band and 5-HT
1AAcceptor all has higher affinity, thereby brings into play dual antidepressant effect, and this kind idea is further extended, and has just formed so-called SSRI ' plus ' method.Under the guidance of this method, the compound that some new role mechanism occurred is in the clinical study stage at present, for example Flibanserin and Vilazodone, and they antidepressant effect can just occur after taking several days.
Summary of the invention
The object of the present invention is to provide a kind of aryl piperazine modified benzo [b] thiophene compound and preparation method and application, this compounds can have 5-HT and 5-HT simultaneously
1AActivity can be used for preparing anti-depression drug.
The present invention is realized by following technical proposals, a kind of aryl piperazine modified benzo [b] thiophene compound, and its structural formula is as follows:
Wherein: Ar is:
R
1For: hydrogen, C
1-C
3Alkyl, hydroxyl, C
1-C
3Alkoxyl group, amino, substituted-amino, halogen, carboxylic acid, ester, acid amides, nitro, itrile group and trihalogenmethyl in a kind of, two or three; R
2For: hydrogen, C
1-C
3Alkyl, five yuan of cycloaliphatic rings, hexa-atomic cycloaliphatic rings, the five-membered ring that contains S, N, O, the hexa-member heterocycle that contains S, N, O, phenyl, substituted-phenyl, hydroxyl, C
1-C
3Alkoxyl group, amino, substituted-amino, halogen, carboxylic acid, ester, acid amides, nitro, itrile group and trihalogenmethyl in a kind of, two or three; X, Y are identical or different to be: C, S, N or O.
Above-mentioned R
1For: in hydrogen, hydroxyl, methoxyl group, amino, substituted-amino, halogen, carboxylic acid, itrile group and the trihalogenmethyl a kind of, two or three; Above-mentioned R
2For: hydrogen, C
1-C
2Alkyl, hydroxyl, C
1-C
2Alkoxyl group, amino, substituted-amino, halogen, carboxylic acid, ester, acid amides, nitro, itrile group and trihalogenmethyl in a kind of, two or three;
Above-mentioned aryl piperazine modified benzo [b] thiophene compound comprises following particular compound:
1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-chloro-phenyl-) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-dichlorophenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-3,5-dimethylphenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-pyridyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-pyrimidyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-p-methoxy-phenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(4-p-methoxy-phenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-trifluoromethyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(1-naphthyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(phenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(3-chloro-phenyl-) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(2, the 3-dichlorophenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(2, the 3-3,5-dimethylphenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(2-pyridyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(2-pyrimidyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(2-p-methoxy-phenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(4-p-methoxy-phenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(3-trifluoromethyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(1-naphthyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(phenyl) piperazine-1-yl]-the 1-propyl alcohol.
The preparation method of above-mentioned aryl piperazine modified benzo [b] thiophene compound, the preparation general formula is:
It is characterized in that comprising following process:
Is in 1～50 times of amount ethanol with the Paraformaldehyde 96 of 1 mole of 3-propionyl benzo [b] thiophene phenol and 1～5 mole and 1～5 mole aryl piperazines hydrochloride in weight ratio, reacts to generate 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-(4-aryl piperazines-1-yl)-1-acetone in 1～80 hour under refluxing; Sodium borohydride with 1 mole 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-(4-aryl piperazines-1-yl)-1-acetone and 0.2～5 mole is to generate 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-(4-aryl piperazines-1-yl)-1-propyl alcohol in 1～20 hour in 0～100 ℃ of reaction in 1～50 times of amount ethanol in weight ratio.
The application of above-mentioned 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-(4-aryl piperazines-1-yl)-1-propyl alcohol, it is characterized in that, the free alkali of this compound or the form of salt are treated dysthymia disorders as antidepressant drugs, and described salt is hydrochloride, hydrobromate, vitriol, trifluoroacetate, mesylate, oxalate or maleate.
Above-mentioned salt is hydrochloride, hydrobromate or maleate.
The invention has the advantages that its preparation process is simple, easy to operate.Prepared compound can have 5-HT and 5-HT simultaneously
1AActivity can be used for preparing antidepressant drugs.
Embodiment
Embodiment 1:1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-p-methoxy-phenyl) piperazine-1-yl]-1-propyl alcohol synthetic
(1) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-p-methoxy-phenyl) piperazine-1-yl]-1-acetone
(0.57g, 3mmol), (0.18g, 6mmol), (0.684g, ethanol 3mmol) (10mL) solution reflux and react 24h down 2-methoxyphenylpiperazderivatives hydrochloride Paraformaldehyde 96 with 3-propionyl benzo [b] thiophene phenol.Add entry (30mL) in the mixture, 10% sodium hydroxide is transferred pH=8.5, dichloromethane extraction (30mL * 3), and washing (50mL * 3), dry (anhydrous sodium sulphate) removes solvent under reduced pressure, gets light yellow oil (0.248g, 21%).
(2) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-p-methoxy-phenyl) piperazine-1-yl]-the 1-propyl alcohol
With 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-p-methoxy-phenyl) piperazine-1-yl]-1-acetone (0.248g, 0.63mmol) be dissolved in the dehydrated alcohol (10mL), add sodium borohydride (0.024g, 0.63mmol), in room temperature reaction 5h, add entry (30mL) cooling in the mixture, dichloromethane extraction (30mL * 3), washing (50mL * 3), in dry (anhydrous sodium sulphate), remove solvent under reduced pressure, get light yellow oil, Thin-layer separation obtains 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-p-methoxy-phenyl) piperazine-1-yl]-1-propyl alcohol (0.20g, 80%).
MS?m/z：396.2，233.1，205.1，163.0，91.1。
Embodiment 2:1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-trifluoromethyl) piperazine-1-yl]-1-propyl alcohol synthetic
(1) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-trifluoromethyl) piperazine-1-yl]-1-acetone
(0.57g, 3mmol), (0.18g, 6mmol), (0.8g, ethanol 3mmol) (10mL) solution reflux and react 30h down 2-3-trifluoromethyl piperazine hydrochloride Paraformaldehyde 96 with 3-propionyl benzo [b] thiophene phenol.Add entry (30mL) in the mixture, 10% sodium hydroxide is transferred pH=8.5, dichloromethane extraction (30mL * 3), washing (50mL * 3), dry (anhydrous sodium sulphate) removes solvent under reduced pressure, light yellow oil, product need not purify and be directly used in down-go on foot reaction.
(2) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-trifluoromethyl) piperazine-1-yl]-the 1-propyl alcohol
The oily matter in last-step is dissolved in the dehydrated alcohol (10mL), the adding sodium borohydride (0.114g, 3mmol), in room temperature reaction 5h, add entry (30mL) cooling in the mixture, dichloromethane extraction (30mL * 3), washing (50mL * 3), dry (anhydrous sodium sulphate), remove solvent under reduced pressure, get light yellow oil, Thin-layer separation obtains 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-trifluoromethyl) piperazine-1-yl]-1-propyl alcohol (0.34g, 26.1%).
MS?m/z：433.9，243.0，171.9，135.0，70.1。
Embodiment 3:1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-dichlorophenyl) piperazine-1-yl]-1-propyl alcohol synthetic
(1) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-dichlorophenyl) piperazine-1-yl]-1-acetone
With 3-propionyl benzo [b] thiophene phenol (0.57g, 3mmol), Paraformaldehyde 96 (0.18g, 6mmol), 2, (0.8g, ethanol 3mmol) (10mL) solution reacts 35h to 3-dichlorophenyl piperazine hydrochloride under refluxing.Add entry (30mL) in the mixture, 10% sodium hydroxide is transferred pH=8.5, dichloromethane extraction (30mL * 3), washing (50mL * 3), dry (anhydrous sodium sulphate) removes solvent under reduced pressure, get light yellow oil, product need not be purified and is directly used in next step reaction.
(2) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-dichlorophenyl) piperazine-1-yl]-the 1-propyl alcohol
The oily matter of previous step is dissolved in the dehydrated alcohol (10mL), add sodium borohydride (0.114g, 3mmol mol) in room temperature reaction 5h, add entry (30mL) cooling in the mixture, dichloromethane extraction (30mL * 3), washing (50mL * 3), dry (anhydrous sodium sulphate) removes solvent under reduced pressure, get light yellow oil, Thin-layer separation obtains 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-dichlorophenyl) piperazine-1-yl]-1-propyl alcohol (0.067g, 5.1%).
MS?m/z：434.2，243.1，174.0，161.1，56.1。
Embodiment 4:1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-3,5-dimethylphenyl) piperazine-1-yl]-1-propyl alcohol synthetic
(1) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-3,5-dimethylphenyl) piperazine-1-yl]-1-acetone
With 3-propionyl benzo [b] thiophene phenol (0.57g, 3mmol), Paraformaldehyde 96 (0.18g, 6mmol), 2, (0.678g, ethanol 3mmol) (10mL) solution reacts 35h to 3-dimethylphenylpiperazinium hydrochloride under refluxing.Add entry (30mL) in the mixture, 10% sodium hydroxide is transferred pH=8.5, dichloromethane extraction (30mL * 3), washing (50mL * 3), dry (anhydrous sodium sulphate) removes solvent under reduced pressure, get light yellow oil, product need not be purified and is directly used in next step reaction.
(2) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2,3-two 3,5-dimethylphenyls) piperazine-1-yl]-the 1-propyl alcohol
The oily matter of previous step is dissolved in the dehydrated alcohol (10mL), (0.114g 3mmol) in room temperature reaction 5h, adds entry (30mL) cooling in the mixture to add sodium borohydride, dichloromethane extraction (30mL * 3), washing (50mL * 3), dry (anhydrous sodium sulphate) removes solvent under reduced pressure, get light yellow oil, Thin-layer separation obtains 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-3,5-dimethylphenyl) piperazine-1-yl]-1-propyl alcohol (0.177g, 15%).
MS?m/z：394.0，203.1，132.0，70.0。
Embodiment 5:1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(4-p-methoxy-phenyl) piperazine-1-yl]-1-propyl alcohol synthetic
(1) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(4-p-methoxy-phenyl) piperazine-1-yl]-1-acetone
(0.57g, 3mmol), (0.18g, 6mmol), (0.684g, ethanol 3mmol) (10mL) solution reacts 35h to 4-methoxyphenylpiperazderivatives hydrochloride to Paraformaldehyde 96 under refluxing with 3-propionyl benzo [b] thiophene phenol.Add entry (30mL) in the mixture, 10% sodium hydroxide is transferred pH=8.5, dichloromethane extraction (30mL * 3), washing (50mL * 3), dry (anhydrous sodium sulphate) removes solvent under reduced pressure, get light yellow oil, product need not be purified and is directly used in next step reaction.
(2) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(4-p-methoxy-phenyl) piperazine-1-yl]-the 1-propyl alcohol
The oily matter of previous step is dissolved in the dehydrated alcohol (10mL), the adding sodium borohydride (0.114g, 3mmol), in room temperature reaction 5h, add entry (30mL) cooling in the mixture, dichloromethane extraction (30mL * 3), washing (50mL * 3), dry (anhydrous sodium sulphate), remove solvent under reduced pressure, get light yellow oil, Thin-layer separation obtains 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(4-p-methoxy-phenyl) piperazine-1-yl]-1-propyl alcohol (0.202g, 17%).
MS?m/z：396.1，234.1，192.1，150.1。
Embodiment 6:1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-chloro-phenyl-) piperazine-1-yl]-1-propyl alcohol synthetic
(1) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-chloro-phenyl-) piperazine-1-yl]-1-acetone
(0.57g, 3mmol), (0.18g, 6mmol), (0.8g, ethanol 3mmol) (10mL) solution reacts 35h to 3-chloro-phenyl-piperazine hydrochloride to Paraformaldehyde 96 under refluxing with 3-propionyl benzo [b] thiophene phenol.Add entry (30mL) in the mixture, 10% sodium hydroxide is transferred pH=8.5, dichloromethane extraction (30mL * 3), washing (50mL * 3), dry (anhydrous sodium sulphate) removes solvent under reduced pressure, get light yellow oil, product need not be purified and is directly used in next step reaction.
(2) 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-chloro-phenyl-) piperazine-1-yl]-the 1-propyl alcohol
Just the oily matter of previous step is dissolved in the dehydrated alcohol (10mL), the adding sodium borohydride (0.114g, 3mmol), in room temperature reaction 5h, add entry (30mL) cooling in the mixture, dichloromethane extraction (30mL * 3), washing (50mL * 3), dry (anhydrous sodium sulphate), remove solvent under reduced pressure, get light yellow oil, Thin-layer separation obtains 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-chloro-phenyl-) piperazine-1-yl]-1-propyl alcohol (0.144g, 12%).
MS?m/z：400.0，223.0，209.0，163.0，91.0。
Claims (6)
1. an aryl piperazine modified benzo [b] thiophene compound, its structural formula is as follows:
Wherein: Ar is:
R
1For: hydrogen, C
1-C
3Alkyl, hydroxyl, C
1-C
3Alkoxyl group, amino, substituted-amino, halogen, carboxylic acid, ester, acid amides, nitro, itrile group and trihalogenmethyl in a kind of, two or three; R
2For: hydrogen, C
1-C
3Alkyl, five yuan of cycloaliphatic rings, hexa-atomic cycloaliphatic rings, the five-membered ring that contains S, N, O, the hexa-member heterocycle that contains S, N, O, phenyl, substituted-phenyl, hydroxyl, C
1-C
3Alkoxyl group, amino, substituted-amino, halogen, carboxylic acid, ester, acid amides, nitro, itrile group and trihalogenmethyl in a kind of, two or three; X, Y are identical or different to be: C, S, N or O.
2. by the described aryl piperazine modified benzo of claim 1 [b] thiophene compound, it is characterized in that: R
1For: in hydrogen, hydroxyl, methoxyl group, amino, substituted-amino, halogen, carboxylic acid, itrile group and the trihalogenmethyl a kind of, two or three; R
2For: hydrogen, C
1-C
2Alkyl, hydroxyl, C
1-C
2Alkoxyl group, amino, substituted-amino, halogen, carboxylic acid, ester, acid amides, nitro, itrile group and trihalogenmethyl in a kind of, two or three.
3. by the described aryl piperazine modified benzo of claim 1 [b] thiophene compound, it is characterized in that: this compound comprises following particular compound:
1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-chloro-phenyl-) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-dichlorophenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2, the 3-3,5-dimethylphenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-pyridyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-pyrimidyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(2-p-methoxy-phenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(4-p-methoxy-phenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(3-trifluoromethyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(1-naphthyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-[4-(phenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(3-chloro-phenyl-) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(2, the 3-dichlorophenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(2, the 3-3,5-dimethylphenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(2-pyridyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(2-pyrimidyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(2-p-methoxy-phenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(4-p-methoxy-phenyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(3-trifluoromethyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(1-naphthyl) piperazine-1-yl]-the 1-propyl alcohol; 1-(the 5-fluorobenzene is [b] thiophene phenol-3-yl also)-2-methyl-3-[4-(phenyl) piperazine-1-yl]-the 1-propyl alcohol.
4. preparation method by described aryl piperazine modified benzo [b] thiophene compound of claim 1, the preparation general formula is:
It is characterized in that comprising following process:
Is in 1～50 times of amount ethanol with the Paraformaldehyde 96 of 1 mole of 3-propionyl benzo [b] thiophene phenol and 1～5 mole and 1～5 mole aryl piperazines hydrochloride in weight ratio, reacts to generate 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-(4-aryl piperazines-1-yl)-1-acetone in 1～80 hour under refluxing; Sodium borohydride with 1 mole 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-(4-aryl piperazines-1-yl)-1-acetone and 0.2～5 mole is to generate 1-(benzo [b] thiophene phenol-3-yl)-2-methyl-3-(4-aryl piperazines-1-yl)-1-propyl alcohol in 1～20 hour in 0～100 ℃ of reaction in 1～50 times of amount ethanol in weight ratio.
5. application by described aryl piperazine modified benzo [b] thiophene compound of claim 1, it is characterized in that: the form from alkali or salt of this compound trip is treated strongly fragrant disease as antidepressant drugs, and described salt is hydrochloride, hydrobromate, vitriol, trifluoroacetate, mesylate or maleate.
6. by the application of described aryl piperazine modified benzo [b] thiophene compound of claim 5, it is characterized in that: salt is hydrochloride, hydrobromate or maleate.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610013548 CN1844120A (en) | 2006-04-27 | 2006-04-27 | Aryl piperazine modified benzo [b] thiophene compounds and their preparation method and use |
| CNB2006101532769A CN100554266C (en) | 2006-04-27 | 2006-09-19 | Aryl piperazine modified benzo [b] thiophene compound and preparation method and application |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8680097B2 (en) | 2008-07-02 | 2014-03-25 | Cspc Zhongqi Pharmaceutical Technology (Shijiazhuang) Co. Ltd. | Benzothiophene alkanol piperazine derivatives and their use as antidepressant |
| US9714232B2 (en) | 2013-12-20 | 2017-07-25 | Sunshine Lake Pharma Co., Ltd. | Substituted piperazine compounds and methods of use thereof |
| US10316025B2 (en) | 2015-06-03 | 2019-06-11 | Sunshine Lake Pharma Co., Ltd. | Substituted piperazine compounds and methods of use and use thereof |
-
2006
- 2006-04-27 CN CN 200610013548 patent/CN1844120A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8680097B2 (en) | 2008-07-02 | 2014-03-25 | Cspc Zhongqi Pharmaceutical Technology (Shijiazhuang) Co. Ltd. | Benzothiophene alkanol piperazine derivatives and their use as antidepressant |
| US9714232B2 (en) | 2013-12-20 | 2017-07-25 | Sunshine Lake Pharma Co., Ltd. | Substituted piperazine compounds and methods of use thereof |
| US10316025B2 (en) | 2015-06-03 | 2019-06-11 | Sunshine Lake Pharma Co., Ltd. | Substituted piperazine compounds and methods of use and use thereof |
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