CN101693711B - 3-(1-piperazinyl)-1,2-benzisothiazole derivative as well as synthesizing method and application thereof - Google Patents
3-(1-piperazinyl)-1,2-benzisothiazole derivative as well as synthesizing method and application thereof Download PDFInfo
- Publication number
- CN101693711B CN101693711B CN2009100757701A CN200910075770A CN101693711B CN 101693711 B CN101693711 B CN 101693711B CN 2009100757701 A CN2009100757701 A CN 2009100757701A CN 200910075770 A CN200910075770 A CN 200910075770A CN 101693711 B CN101693711 B CN 101693711B
- Authority
- CN
- China
- Prior art keywords
- compound
- piperazinyl
- benzisothiazole
- epoxy chloropropane
- arh
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a 3-(1-piperazinyl)-1,2-benzisothiazole derivative as well as a synthesizing method and application thereof in preparing an antipsychotic drug. The method comprises the following steps: (a) enabling 7-hydroxy-3,4-dihydro-2(1H)-carbostyril to react with (+/-)-epoxy chloropropane, (-)-epoxy chloropropane and (+)-epoxy chloropropane under the action of a basic catalyst to produce an object; (b) stirring the object obtained in the step (a) with 3-(1-piperazinyl)-1,2-benzisothiazole in an alcoholic solution containing less than 5 carbon atoms by heating, reacting for 2-8h, cooling, reducing the pressure, concentrating, and purifying by a silica gel column chromatography to obtain a compound I. The invention provides a new compound which is prepared by simple operation steps and has mild reaction condition and higher yield in each step, wherein a cheap solvent adopted during the preparation is easy to obtain. .
Description
Technical field
The present invention relates to compound and preparation method and use thereof, 3-(1-piperazinyl)-1 specifically, 2-benzisothiazole derivatives and preparation method and use thereof.
Background technology
Psychosis belongs to common disease, frequently-occurring disease.Be used for the treatment of psychotic medicine at present typical antipsychotics and atypical antipsychotic are arranged.Because atypical antipsychotic is having significant superiority aspect curative effect and the side effect, thereby is subjected to clinical extensive favor.Be used at present clinical atypical antipsychotic and mainly contained leoponex, risperidone, olanzapine, Quetiapine, neat piperazine west ketone, Sertindole.Ziprasidone wherein (Ziprasidone) belongs to serotonin and dopamine-receptor antagonist, especially 5-HT A2/DA D2 acceptor is had strong avidity.This medicine no matter to acute or chronic, just send out or recur schizophrenia good curative effect is all arranged, also effective to schizophrenia related symptoms (comprise audiovisual illusion, vain hope, motivation lack and escape society).This medicine is compared with traditional antipsychotic drug, except that improving the positive symptom, also can improve negative symptoms, improves cognitive function, and its untoward reaction particularly extrapyramidal symptoms alleviates greatly, and tolerance obviously improves.Yet because the continuous growth of the ill rate of psychosis, the antipsychotics kind on the market is deficient relatively, has seriously restricted the sneakerization of clinical application thus.
Summary of the invention
Purpose of the present invention will provide a kind of active compound of atypical antipsychotic that has exactly, and a kind of method of synthetic this compound is provided simultaneously, and the application of this compound in pharmaceutical preparation.
The object of the present invention is achieved like this:
Compound provided by the present invention is 3-(1-piperazinyl)-1, the 2-benzisothiazole derivatives, and its general formula is:
Wherein
Wherein:
The chemical name of Compound I is:
7-[3-[4-(1,2-benzisothiazole-3-yl)-1-piperazinyl]-2-hydroxyl propoxy-]-3,4-dihydro-2 (1H)-quinolone.
Structural formula is:
The chemical name of Compound I I is: 1-(benzhydrylamine base)-3-[4-(1,2-benzisothiazole-3-yl)-1-piperazinyl]-the 2-propyl alcohol.
Structural formula is:
The chemical name of compound III is: 7-[2-[4-(1,2-benzisothiazole-3-yl)-1-piperazinyl] oxyethyl group]-3,4-dihydro-2 (1H)-quinolone.
Structural formula is:
The chemical name of compound IV is: 7-[3-[4-(1,2-benzisothiazole-3-yl)-1-piperazinyl] propoxy-]-3,4-dihydro-2 (1H)-quinolone.
Structural formula is:
The chemical name of compound V is: 7-[4-[4-(1,2-benzisothiazole-3-yl)-1-piperazinyl] butoxy]-3,4-dihydro-2 (1H)-quinolone.
Chemical structure is:
The present invention provides a kind of synthetic method of above-claimed cpd simultaneously:
(1) synthetic compound I may further comprise the steps:
(a) preparation intermediate 7-(1, the 2-glycidoxy)-3,4-dihydro-2 (1H)-quinolone (abbreviation compound b):
With 7-hydroxyl-3,4-dihydro-2 (1H)-quinolone (abbreviation compound a) and (±)-epoxy chloropropane, (-)-epoxy chloropropane and (+)-epoxy chloropropane under the effect of basic catalyst, reacting generating compound b;
(b) according to 1: 1 mol ratio, with above-mentioned a step gained compound b and 3-(1-piperazinyl)-1,2-benzisothiazole (abbreviation compound c) is in the alcoholic solution of≤5 carbon atoms, heated and stirred was reacted 2-8 hour, cooling, concentrating under reduced pressure, purification by silica gel column chromatography gets Compound I.
Its chemical equation is as follows:
The above-mentioned alcoholic solution that is less than 5 carbon atoms comprises methyl alcohol, ethanol, n-propyl alcohol, Virahol, propyl carbinol, the trimethyl carbinol, 2-butanols.Wherein be preferred with the propyl carbinol.
Above-claimed cpd a, compound c are the important intermediate of medicine chemical material, can directly buy in medical market.
(2) synthetic compound II may further comprise the steps:
(a) preparation intermediate 1-benzhydrylamine base-3-chloro-2-propyl alcohol (abbreviation Verbindung)
According to 1: 1: 1 mol ratio, with benzhydrylamine (abbreviation compound d) and epoxy chloropropane, methanol mixed, in the alcoholic solution of≤3 carbon atoms, reacted 24～48 hours, get Verbindung.
(b) according to 1: 1 mol ratio, with above-mentioned a step gained Verbindung and 3-(1-piperazinyl)-1,2-benzisothiazole (abbreviation compound c), with DMF (N, dinethylformamide) is solvent, under salt of wormwood/potassiumiodide katalysis, at 45～65 ℃, reacted 18～36 hours, cooling adds distilled water diluting, uses ethyl acetate extraction, concentrating under reduced pressure gets Compound I I.
Its chemical equation is as follows:
Above-claimed cpd d is the important intermediate of medicine chemical material, can directly buy in medical market.
(3) synthetic compound III, IV, V may further comprise the steps:
(a) according to 1: 7.5 mol ratio, with 7-hydroxyl-3,4-dihydro-2 (1H)-quinolone (compound a) and n=2 or 3 or 4 two bromoalkanes, in the alcoholic solution of≤3 carbon atoms, mix, under the effect of catalyzer, reacted 2-6 hour, cooling, concentrating under reduced pressure, purification by silica gel column chromatography, make 7-bromine oxethyl-3 respectively, 4-dihydro-2 (1H)-quinolone (being called for short compound f), 7-bromine propoxy--3,4-dihydro-2 (1H)-quinolone (being called for short compound g), 7-bromine butoxy-3,4-dihydro-2 (1H)-quinolone (being called for short compound h);
(b) according to 1: 1 mol ratio, with above-mentioned a step gained compound respectively with 3-(1-piperazinyl)-1,2-benzisothiazole (compound c) mixes, and is solvent with DMF, under salt of wormwood/potassiumiodide katalysis, at 45～65 ℃, reacted cooling 18～36 hours, add distilled water diluting, use ethyl acetate extraction, concentrating under reduced pressure gets compound III, IV, V.
Its chemical equation is as follows:
The optional sodium ethylate of above-mentioned catalyzer, sodium methylate, sodium hydroxide.Wherein be preferred with the sodium ethylate.
The inventive method step is simple to operate, the reaction conditions gentleness, and it is higher that each goes on foot productive rate, and agents useful for same is cheap and easy to get.
The compounds of this invention is to dopamine D
2, 5-HT
2C, 5-HT
1A, 5-HT
1DAnd α
1Adrenoceptor has very strong affinity; To histamine H
1Acceptor has moderate affinity.
Test shows that The compounds of this invention has and the identical pharmacologically actives of novel atypical antipsychotic such as Aripiprazole, Ziprasidone.
Therefore, the applicant has invented this novel application of compound, and promptly this compound is used to prepare the atypical antipsychotic preparation.
The pharmacologically active of The compounds of this invention has obtained proof by following pharmacological testing.
Trial drug and reagent:
The test group medication:
Embodiment 1,2,3,4,5 made Compound I, Compound I I, compound III, compound IV, compound V.
Positive controls medication: Ziprasidone (Shenhuaxi Pharmaceutical Co., Ltd., Chongqing, product batch number 20071205).
Injection apomorphine hydrochloride (Shenyang No.1 Pharmaceutical Factory, Dongbei Pharmaceutical Group Co., product batch number 20071016).
Ascorbic acid solution.
Experimental animal:
Test method:
70 of adult male SD rats are divided into the blank group at random, positive drug control group, experimental group 1 and experimental group 2, experimental group 3, experimental group 4, experimental group 5, totally 7 groups.
With the common dose subcutaneous injection, press 1mg/kg abdominal injection apomorphine hydrochloride after 1.5 hours, 0.1% ascorbic acid solution.After the injection apomorphine hydrochloride, respectively 5,15,25,35 and 45min observe the social behavior of rat, keep the score by following method, movable note is 1 minute in cage, discontinuous nasil performance note 2 minutes with the continuous nasil performance note of discontinuous mouth action 3 minutes, is licked, machonnement note 4 minutes.PTS is low more, and the expression activity is strong more.
Statistical processing and analysis (SPAN) in an embodiment: select X for use
2The SPSS10.0 computed in software is adopted in check, is that difference has statistical significance with P＜0.05.
Test-results sees table 1 for details:
P＜0.05
Above-mentioned test shows that The compounds of this invention has the pharmacologically active of antipsychotic, and its activity intensity and Ziprasidone are suitable.And, do not see the dominance toxic side effect through acute, sub-acute toxicity test.
This shows that medicine of the present invention can be used for preparing the atypical antipsychotic preparation.Be used for the treatment of schizophrenia type psychosis; Especially can be used for removing or improve that insane anxiety, anxiety, social activity or emotion are shunk back and symptom such as fear.
The compounds of this invention or its pharmaceutical salts can add pharmaceutical excipient or thinner and make tablet, capsule, oral preparations such as oral liquid according to the practice of pharmacy of routine.Wherein the auxiliary material used of tablet can be lactose or starch, Magnesium Stearate; Capsule can be made thinner with lactose or dry starch; Can add emulsifying agent and suspending agent in the oral liquid.Can also add sweeting agent or correctives in case of necessity.
The weight ratio of The compounds of this invention or its pharmaceutical salts and various auxiliary materials generally is controlled at 1: 6 to 2: 1 scope in pharmaceutical preparation, and effect was better in 1: 4 to 1: 1.
Under any circumstance, selected ratio all depends on the solubleness of medicine, the dosage and the route of administration of expection.
The compounds of this invention also can be prepared into the parenteral administration preparation, comprises intramuscular injection or quiet notes preparation, need make
Sterile solution, the pH of control solution during quiet notes administration, is adjusted to isotonic concentration with solution.
When the antipsychotics among the present invention was used for the treatment of schizophrenia, oral dosage was determined by the doctor.Simultaneously, dosage changes with age, body weight and patient's the individual difference and the severity of symptom.As a rule, schizoid day oral effective dose of treatment is in 5～500mg scope.General single clothes or the divided dose of adopting, oral or drug administration by injection, dosage control is at 5～100mg.In indivedual cases, can not be subjected to this dose limitation.
Following examples are used for that the present invention is described further, and it is not to be qualification to protection domain of the present invention.
Embodiment
Embodiment 1 synthetic compound I
(a) preparation midbody compound b:
In two mouthfuls of flasks of 50mL, add dehydrated alcohol 5mL, sodium Metal 99.5 0.14g (6.10mmol), react to sodium Metal 99.5 and disappear, add compound a (buy from market, manufacturing enterprise is Hangzhou wide woods Bioceuticals Inc.) 1.0g (6.10mmol), stir 30min, add epoxy chloropropane 1.38g (15mmol), stirring reaction 3 hours, concentrating under reduced pressure, purification by silica gel column chromatography, get compound b (0.6g, 51%).
(b) in two mouthfuls of flasks of 50mL, add above-claimed cpd b 0.30g (1.37mmol), compound c (is buied from market, manufacturing enterprise is Shanghai Haisun Chemical Technologies Co., Ltd) 0.32g (1.37mmol), propyl carbinol 10mL, stirring heating, reacted 6 hours, cooling, concentrating under reduced pressure, purification by silica gel column chromatography, get white crystalline compound I (0.38g, 63%).
1H-NMR(500MHz，CDCl
3，δ)：2.62(m，4H，11′，13′-CH
2)，2.69(m，2H，4-CH
2)，2.91(m，4H，3，c-CH
2)，3.58(m，4H，10′，12′-CH
2)，3.99(m，1H，a-CH
2)，4.16(m，1H，b-CH
2)，6.34(d，1H，8-ArH)，6.57(m，1H，6-ArH)，7.07(d，1H，5-ArH)，7.37(t，1H，6′-ArH)，7.48(t，1H，5′-ArH)，7.82(d，1H，7′-ArH)，7.91(d，1H，4′-ArH)。
Embodiment 2 synthetic compound II
(a) preparation midbody compound e:
In the 50mL flask, add compound d (market is buied) 0.44g (2.32mmol), epoxy chloropropane 0.22g (2.32mmol), methyl alcohol 10mL reacted 36 hours, and purification by silica gel column chromatography gets Verbindung (0.46g, 76%).
(b) in the 250mL flask, add Verbindung 4.6g (16.9mmol), compound c 3.7g (16.9mmol), DMF 100mL, yellow soda ash 1.8g (16.9mmol), potassiumiodide 0.3g.Stirring heating keeps 60 ℃, reacts 24 hours, and cooling adds distilled water 100mL, ethyl acetate extraction (30mL * 3), and concentrating under reduced pressure, purification by silica gel column chromatography gets yellow oily Compound I I (4.6g, 59%).
1H-NMR(500MHz，CDCl
3，δ)：2.39(dd，1H，10a-CH
2)，2.60(m，4H，11′，13′-CH
2)，2.70(t，dd，1H，10b-CH
2)，2.84(m，2H，8-CH
2)，3.55(m，4H，10′，12′-CH
2)，3.92(m，1H，9-CH
2)，4.82(s，1H，7-CH
2)，7.18(m，2H，4-ArH)，7.28(m，4H，2，6-ArH)，7.33(m，1H，6′-ArH)，7.40(m，4H，3，5-ArH)，7.44(t，1H，5′-ArH)，7.78(d，1H，7′-ArH)，7.87(d，1H，4′-ArH)。
Embodiment 3 synthetic compound III
(a) synthetic compound f:
In the 50mL flask, add dehydrated alcohol 5mL, sodium Metal 99.5 0.014g (0.61mmol), room temperature reaction to sodium Metal 99.5 disappears.Add compound a 0.1g (0.61mmol), molten entirely, stir 30min, add glycol dibromide (4.53mmol), stirring heating was reacted 3 hours, concentrating under reduced pressure, purification by silica gel column chromatography gets target product 0.12g, yield 73%.
(b) synthetic compound III
With above-mentioned target product 1.2g (4.4mmol), compound c 1.0g (0.44mmol), DMF50mL, salt of wormwood 18g (13.2mmol), potassiumiodide 1g.Stirring heating keeps 50 ℃, reacts 36 hours, and cooling adds distilled water 100mL, ethyl acetate extraction (30mL * 3), and concentrating under reduced pressure, purification by silica gel column chromatography gets white solid compound III 1.3g, yield 71%.
1H-NMR(500MHz，CDCl
3，δ)：2.62(t，2H，4-CH
2)，2.72(t，4H，11′，13′-CH
2)，2.80(t，4H，3，b-CH
2)，3.59(t，4H，10′，12′-CH
2)，4.12(t，2H，a-CH
2)，6.40(d，1H，8-ArH)，6.56(m，1H，6-ArH)，7.05(d，1H，5-ArH)，7.36(t，1H，6′-ArH)，7.46(t，1H，5′-ArH)，7.81(d，1H，7′-ArH)，7.91(d，1H，4′-ArH)，8.52(s，1H，NH)。
Embodiment 4 synthetic compound IV
(a) synthetic compound g:
In the 50mL flask, add dehydrated alcohol 5mL, sodium Metal 99.5 0.014g (0.61mmol), room temperature reaction to sodium Metal 99.5 disappears.Add compound a 0.1g (0.61mmol), molten entirely, stir 30min, add 1,2-dibromopropane (4.53mmol), stirring heating was reacted 4 hours, concentrating under reduced pressure, purification by silica gel column chromatography gets target product 0.13g, yield 81%.
(b) synthetic compound IV
Get above-claimed cpd g 1.0g (3.5mmol), compound c 0.8g (3.5mmol), DMF50mL, salt of wormwood 1.1g (10.5mmol), potassiumiodide 1g.Stirring heating keeps 60 ℃, reacts 18 hours, and cooling adds distilled water 100mL, ethyl acetate extraction (30mL * 3), and concentrating under reduced pressure, purification by silica gel column chromatography gets white solid compound IV 1g, yield 70%.
1H-NMR(500MHz，CDCl
3，δ)：2.02(m，2H，b-CH
2)，2.62(m，4H，4，c-CH
2)，2.72(t，4H，11′，13′-CH
2)，2.80(t，2H，3-CH
2)，3.59(t，4H，10′，12′-CH
2)，4.03(t，2H，a-CH
2)，6.31(d，1H，8-ArH)，6.56(m，1H，6-ArH)，7.05(d，1H，5-ArH)，7.36(t，1H，6′-ArH)，7.48(t，1H，5′-ArH)，7.81(d，1H，7′-ArH)，7.91(d，1H，4′-ArH)。
Embodiment 5 synthetic compound V
(a) synthetic compound h:
In the 50mL flask, add dehydrated alcohol 5mL, sodium Metal 99.5 0.014g (0.61mmol), room temperature reaction to sodium Metal 99.5 disappears.Add compound a 0.1g (0.61mmol), molten entirely, stir 30min, add 1,2-dibromobutane (4.53mmol), stirring heating was reacted 4 hours, concentrating under reduced pressure, purification by silica gel column chromatography gets target product 14g, yield 70%.
(b) synthetic compound V
Get above-claimed cpd h 1.0g (3.5mmol), compound c 0.8g (3.5mmol), DMF50mL, salt of wormwood 1.1g (10.5mmol), potassiumiodide 1g.Stirring heating keeps 45 ℃, reacts 36 hours, and cooling adds distilled water 100mL, ethyl acetate extraction (30mL * 3), and concentrating under reduced pressure, purification by silica gel column chromatography gets white solid compound IV 1.4g, yield 64%.
1H-NMR(500MHz，CDCl
3，δ)：1.74(m，2H，c-CH
2)，1.84(m，2H，b-CH
2)，2.51(t，2H，d-CH
2)，2.62(t，2H，4-CH
2)，2.70(s，4H，10′，12′-CH
2)，2.90(t，2H，3-CH
2)，3.72(s，4H，11′，13′-CH
2)，3.97(t，2H，a-CH
2)，6.27(d，1H，8-ArH)，6.53(m，1H，6-ArH)，7.05(d，1H，5-ArH)，7.27(t，1H，NH)，7.36(t，1H，6′-ArH)，7.47(t，1H，5′-ArH)，7.81(d，1H，7′-ArH)，7.91(d，1H，4′-ArH)。
Following examples have been enumerated several formulations of The compounds of this invention:
Embodiment 6: medicinal tablet of the present invention:
20 kilograms of The compounds of this invention I, method for preparing tablet thereof adds starch routinely, and dextrin, magnesium stearate etc. are mixed and made into wet grain, and the machine punching press is in blocks, and every contains The compounds of this invention I 20mg.
Embodiment 7: the The compounds of this invention oral liquid:
With being dissolved in the 1000ml water of The compounds of this invention II, add suitable solubility promoter, make the aqueous solution of 2.5% concentration, heating for dissolving mixes, and in the 10ml medicine bottle of packing into, seals, sterilizes.
Pharmaceutical dosage form of the present invention is not limited solely to this, and it can be prepared into more formulation, as dripping pill, capsule, soft capsule, sustained-release preparation or the like.
Claims (3)
1. a 3-(1-piperazinyl)-1, the synthetic method of 2-benzisothiazole derivatives, the general formula of this derivative is:
Wherein
, it is characterized in that it may further comprise the steps:
(a) preparation intermediate 7-(1, the 2-glycidoxy)-3,4-dihydro-2 (1H)-quinolone:
With 7-hydroxyl-3,4-dihydro-2 (1H)-quinolone and (±)-epoxy chloropropane, (-)-epoxy chloropropane and (+)-epoxy chloropropane are under the effect of basic catalyst, and reaction generates target compound;
(b) according to 1: 1 mol ratio, with above-mentioned a step gained target compound and 3-(1-piperazinyl)-1, the 2-benzisothiazole, in the alcoholic solution of≤5 carbon atoms, heated and stirred was reacted 2～8 hours, cooling, concentrating under reduced pressure, purification by silica gel column chromatography gets Compound I.
2. the synthetic method of Compound I according to claim 1 is characterized in that the described alcoholic solution that is less than 5 carbon atoms is a propyl carbinol.
3. a 3-(1-piperazinyl)-1, the synthetic method of 2-benzisothiazole derivatives, the general formula of derivative is:
Wherein
, it is characterized in that it may further comprise the steps:
(a) preparation intermediate 1-benzhydrylamine base-3-chloro-2-propyl alcohol:
According to 1: 1: 1 mol ratio, with benzhydrylamine and epoxy chloropropane, methanol mixed, in the alcoholic solution of≤3 carbon atoms, reacted 24～48 hours, target compound;
(b) according to 1: 1 mol ratio, with above-mentioned a step gained target compound and 3-(1-piperazinyl)-1, the 2-benzisothiazole is a solvent with DMF, under salt of wormwood/potassiumiodide katalysis, at 45～65 ℃, reacted cooling 18～36 hours, add distilled water diluting, use ethyl acetate extraction, concentrating under reduced pressure gets Compound I I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100757701A CN101693711B (en) | 2009-10-23 | 2009-10-23 | 3-(1-piperazinyl)-1,2-benzisothiazole derivative as well as synthesizing method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009100757701A CN101693711B (en) | 2009-10-23 | 2009-10-23 | 3-(1-piperazinyl)-1,2-benzisothiazole derivative as well as synthesizing method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101693711A CN101693711A (en) | 2010-04-14 |
| CN101693711B true CN101693711B (en) | 2011-08-17 |
Family
ID=42092720
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009100757701A Active CN101693711B (en) | 2009-10-23 | 2009-10-23 | 3-(1-piperazinyl)-1,2-benzisothiazole derivative as well as synthesizing method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101693711B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4458076A (en) * | 1983-05-31 | 1984-07-03 | Hoechst-Roussel Pharmaceuticals | 3-(4-Piperidinyl)-1,2-benzisothiazoles |
| CN101302214A (en) * | 2007-05-11 | 2008-11-12 | 江苏国华投资有限公司 | Aralkyl piperidine (piperazidine) derivate and use thereof in mental disease treatment |
| CN101607959A (en) * | 2009-06-18 | 2009-12-23 | 上海医药工业研究院 | The dihydroquinoline ketone derivatives, its preparation method and be the pharmaceutical composition of activeconstituents with this compound |
-
2009
- 2009-10-23 CN CN2009100757701A patent/CN101693711B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4458076A (en) * | 1983-05-31 | 1984-07-03 | Hoechst-Roussel Pharmaceuticals | 3-(4-Piperidinyl)-1,2-benzisothiazoles |
| CN101302214A (en) * | 2007-05-11 | 2008-11-12 | 江苏国华投资有限公司 | Aralkyl piperidine (piperazidine) derivate and use thereof in mental disease treatment |
| CN101607959A (en) * | 2009-06-18 | 2009-12-23 | 上海医药工业研究院 | The dihydroquinoline ketone derivatives, its preparation method and be the pharmaceutical composition of activeconstituents with this compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101693711A (en) | 2010-04-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2468025C2 (en) | Therapeutic agents | |
| CN100402523C (en) | Heterocyclic compounds and antitumor drugs containing the same as the active ingredient | |
| CN101486703B (en) | Flavone compound with antineoplastic activity, preparation thereof and uses thereof | |
| CN101948458B (en) | Baicalein derivatives with antitumor activity and application thereof in medicines | |
| CN108884101A (en) | Substituted Pyrrolopyrimidine CDK inhibitor, pharmaceutical composition and their purposes comprising it | |
| CN102186833A (en) | MIF modulators | |
| ZA200210114B (en) | Substituted pyrrolopyridinone derivatives useful as phosphodiesterase inhibitors. | |
| CN112110936B (en) | Tetrahydroquinoline derivative and preparation method and application thereof | |
| CN104059039A (en) | Fused ring compound with GPR40 receptor function adjusting effect | |
| JP2021505681A (en) | A novel pyrimidine derivative showing a growth inhibitory effect on cancer cells and a pharmaceutical composition containing the same. | |
| CN100361975C (en) | Novel 5-hydroxy-3-carboxylate indoles derivant and method for preparing the same | |
| EP2880024A1 (en) | Griseofulvin derivatives | |
| CN101417995A (en) | Phenoxy pyrimidine derivates and its production and use | |
| CN101693711B (en) | 3-(1-piperazinyl)-1,2-benzisothiazole derivative as well as synthesizing method and application thereof | |
| DK2610257T3 (en) | DI-IMIDED DERIVATIVE OF BERBAMINE AND METHOD FOR PREPARING AND USING THEREOF | |
| CN109232362B (en) | Aromatic heterocyclic derivative and application thereof in medicines | |
| EP3946614A1 (en) | Fused polycyclic pyridone compounds as influenza virus replication inhibitors | |
| SK2722002A3 (en) | Use of bis-sulfonamides for producing medicaments used for preventing or treating hyperlipidaemia | |
| JP2022517984A (en) | Intracyclic thiamidinoamide-arylamide compounds and their use for the treatment of hepatitis B | |
| KR20110074574A (en) | The 1-butyl-2-hydroxyaralkyl piperazine derivatives and the uses as anti-depression medicine thereof | |
| CN101870696A (en) | N-aryl piperazine derivative having double activity of dopamine D2 and 5-HT2a | |
| CN103864680A (en) | Chloroxoquinoline derivatives with anti-tumor activity | |
| US6881841B2 (en) | Dibenzosuberanyl piperazine derivatives and drug-resistance overcoming agents containing the derivatives | |
| JP2023528170A (en) | Alkenylpyrimidine compound, preparation method and use thereof | |
| CN106810553B (en) | 3- (4, 5-substituted aminopyrimidine) phenyl derivative and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Shijiazhuang No.4 Pharmaceutical Co., Ltd. Assignor: Du Yumin Contract record no.: 2012130000002 Denomination of invention: 3-(1-piperazinyl)-1,2-benzisothiazole derivative as well as synthesizing method and application thereof Granted publication date: 20110817 License type: Exclusive License Open date: 20100414 Record date: 20120110 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20161205 Address after: Yang Zi economic and Technological Development Zone of Hebei Province, Shijiazhuang City Industrial northbound 052165 Road West Patentee after: Hebei Guolong Pharmaceutical Co., Ltd. Address before: 050017 Zhongshan East Road, Hebei, No. 361 Hebei Medical University, Patentee before: Du Yumin |