CN103012314A - Sulfonamide compound and preparation method as well as application thereof - Google Patents

Sulfonamide compound and preparation method as well as application thereof Download PDF

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CN103012314A
CN103012314A CN2012105753944A CN201210575394A CN103012314A CN 103012314 A CN103012314 A CN 103012314A CN 2012105753944 A CN2012105753944 A CN 2012105753944A CN 201210575394 A CN201210575394 A CN 201210575394A CN 103012314 A CN103012314 A CN 103012314A
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compound
sulfonamides
alkyl
acceptable salt
preparation
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CN103012314B (en
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梁艳书
朱英杰
郭桂梅
路亮
龙丽
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Tianjin University of Commerce
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Abstract

The invention discloses a sulfonamide compound and a preparation method as well as application thereof, and provides the sulfonamide compound with hypoglycemic activity and the preparation method thereof. The sulfonamide compound has a structure of a general formula I, wherein X is S or O atoms, n is 1, 2, 3 or 4, R1 and R2 are simultaneously or respectively hydrogen or C1-C4 alkyl groups, and R3, R4 and R5 are simultaneously or respectively one out of hydrogen, C1-C6 alkyl groups, C1-C4 alkoxyl groups, halogens, single or multi-halogen replaced C1-C4 alkyl groups, cyan, phenyl groups, single halogenated phenyl groups, C1-C4 alkoxyl phenyl group, C1-C4 alkyl sulfonyl groups and bromomethyl carbonyl groups. The sulfonamide compound with the structure of the formula I and pharmaceutically acceptable salts thereof have obvious effect in terms of resisting hyperglycemia.

Description

Sulfonamides compound and its preparation method and application
Technical field
The invention belongs to medical technical field, in particular, relate to a class and have compound of hypoglycemic activity and its preparation method and application.
Background technology
According to the diabetes of IDF (IDF) announcement and data and the reckoning of impaired glucose tolerance (IGT), diabetic subject's number was 1.94 hundred million in 2003, then will reach 3.33 hundred million in 2025; The IGT number was 3.14 hundred million in 2003, and 2025 then will be up to 4.72 hundred million.In recent years, along with improving constantly and the change of dietary structure of living standards of the people, extensive growth has also appearred in China diabetic subject's quantity.
Antidiabetic medicine in clinical use mainly contains insulin type, sulfonylurea, N1,N1-Dimethylbiguanide class and the alpha-glucosidase inhibitor that recently goes on the market and Studies of The Insulin Sensitizer Thiazolidinediones medicine etc. at present.These medicines have good curative effect, but still have the medicine life-time service and the shortcoming that can not keep long-term efficacy that causes, and cause that easily hypoglycemia, body weight increase and produce many untoward reactions such as liver toxicity.
Therefore, seeking new ofhypoglycemic medicine is one of focus of domestic and international the world of medicine research.
Summary of the invention
The sulfonamides compound and the pharmacy acceptable salt thereof that provide a class to have hypoglycemic activity is provided one object of the present invention.
A further object of the present invention is to provide the preparation method of a class sulfonamides compound and pharmacy acceptable salt thereof.
Another object of the present invention is to provide the pharmaceutical composition take a class sulfonamides compound and pharmaceutical salts thereof as main active ingredient.
A further object of the invention is to provide the application as the ofhypoglycemic medicine aspect of a class sulfonamides compound and pharmaceutical salts thereof.
Now in conjunction with the object of the invention, content of the present invention is described in detail.
One class sulfonamides compound has the structure of following formula I:
Figure BDA00002647154000021
Wherein:
X is S or O atom;
N=1,2,3 or 4;
R 1With R 2Be hydrogen or C1-C4 alkyl at the same time or separately, preferred hydrogen, methyl, ethyl or sec.-propyl.
R 3, R 4With R 5Be that hydrogen, C1-C6 alkyl, C1-C4 alkoxyl group, halogen, list or many halogens replace any in C1-C4 alkyl, cyano group, phenyl, single halogenophenyl, C1-C4 alkoxyl phenyl, C1-C4 alkyl sulphonyl, the brooethyl carbonyl at the same time or separately.Preferred hydrogen, methyl, ethyl, propyl group, sec.-propyl, butyl, the tertiary butyl, amyl group, methoxyl group, oxyethyl group, propoxy-, fluorine, chlorine, bromine, trifluoromethyl, cyano group, phenyl, tolyl, bromophenyl, methoxyphenyl, methylsulfonyl or brooethyl carbonyl.
The preferred following compound of sulfonamides compound of the present invention:
I-1, N-(2-(4-(benzothiazole-2-yl) piperazine-1-yl) ethyl)-3, the 5-dimethyl benzene sulfonamide, structural formula is
I-2, N-(3-(4-(benzothiazole-2 base) piperazine-1-yl) propyl group)-3-cyano group-4-fluorobenzene sulphonamide, structural formula is
Figure BDA00002647154000031
I-3, N-(4-(4-(benzothiazole-2-yl) piperazine-1-yl) butyl)-4 '-methoxyl group biphenylyl-3-sulphonamide, structural formula is
Figure BDA00002647154000032
I-4, N-(5-(4-(benzothiazole-2-yl) piperazine-1-yl) amyl group)-2,6-two chloro-4-(trifluoromethyl) benzsulfamides, structural formula is
I-5, N-(2-(4-(benzoxazoles-2-yl) piperazine-1-yl) ethyl)-4-fluoro-3-methyl benzenesulfonamide, structural formula is
Figure BDA00002647154000034
I-6, N-(3-(4-(benzoxazoles-2-yl) piperazine-1-yl) propyl group)-4-(methylsulfonyl) benzsulfamide, structural formula is
I-7, N-(4-(4-(benzoxazoles-2-yl) piperazine-1-yl) butyl)-3-(2-acetyl bromide) benzsulfamide, structural formula is
Figure BDA00002647154000036
I-8, N-(5-(4-(benzoxazoles-2-yl) piperazine-1-yl) the amyl group)-3-t tertiary butyl-5-propoxy-benzsulfamide, structural formula is
Figure BDA00002647154000037
I-9, N-(3-(4-(benzothiazole-2-yl)-2,6-dimethyl-piperizine-1-yl) propyl group)-5-ethyl-2-methoxybenzenesulphoismide, structural formula is
Figure BDA00002647154000038
I-10, N-(3-(4-(benzoxazoles-2-yl)-2,6-dimethyl-piperizine-1-yl) propyl group)-4 '-bromine biphenylyl-4-sulphonamide, structural formula is
A kind of preparation method of sulfonamides compound comprises the steps:
(1) have the benzo five-membered heterogeneous ring compound that contains piperazine of general formula II and alkyl chloride aminated compounds in the presence of acid binding agent, in solvent, 0～110 ℃ of reaction response obtains having the compound of general formula III;
(2) above-mentioned compound with general formula III and the benzene sulfonyl chloride of the replacement with general formula IV are in the presence of acid binding agent, and in solvent, 0～110 ℃ of reaction obtains having the sulfonamides compound of formula I;
Syntheti c route is expressed as follows:
Figure BDA00002647154000042
Wherein, n, X, R 1, R 2, R 3, R 4, R 5Such as aforementioned definitions.
Described alkyl chloride aminated compounds is haloalkyl amine, described acid binding agent is triethylamine, pyridine, salt of wormwood, yellow soda ash, sodium bicarbonate, saleratus, sodium hydroxide or potassium hydroxide, and described solvent is methylene dichloride, trichloromethane, acetonitrile, tetrahydrofuran (THF), DMF or toluene.
The described sulfonamides compound pharmacy acceptable salt of one class, this pharmacy acceptable salt are compound and mineral acid or the organic acid institute salify of general formula I.Wherein particularly preferred salt is: hydrochloride, hydrobromate, hydriodate, vitriol, hydrosulfate, phosphoric acid salt, hydrophosphate, acetate, propionic salt, butyrates, lactic acid salt, mesylate; tosilate, maleate; benzoate, succinate, tartrate, Citrate trianion, fumarate, taurate, amino acid salts, gluconate, etc.
The preparation method of the described sulfonamides compound pharmacy acceptable salt of one class, comprise the steps: described sulfonamides compound is dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, drip mineral acid or organic acid, make pharmacy acceptable salt.
Specifically the various compounds that contain general formula I are dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, under ice-water bath, drip the salt acid ether to pH=2, make hydrochloride; Or the various compounds that contain general formula I are dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, and adding and the equimolar gluconic acid of the compound that contains general formula I, heated and stirred gets its gluconate; Or the compound that will contain general formula I is dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, drips the vitriol oil to pH=3 under ice-water bath, makes vitriol.
A kind of pharmaceutical composition with hypoglycemic activity, it comprises the described pharmacy acceptable salt that contains the compound of formula I or contain the compound of described formula I for the treatment of significant quantity.
Contain the compound of formula I in the application aspect hypoglycemic drug.
Contain the pharmacy acceptable salt of compound of formula I in the application aspect hypoglycemic drug.
The compound that contains formula I of the present invention is effective for the human disease that causes because of hyperglycemia for the treatment of.Although compound of the present invention can be without the direct administration of any configuration, described various compounds preferably use with the form of pharmaceutical preparation, and route of administration can be non-enteron aisle approach (such as vein, muscle administration) and oral administration.
The pharmaceutical composition preparation method of the compounds of this invention is as follows: Application standard and conventional technology; the compound that contains formula I of the present invention acceptable solid or liquid vehicle on technology of pharmaceutics are combined, and make it at random on technology of pharmaceutics acceptable auxiliary and vehicle and be combined and be prepared into particulate or microballoon.Solid dosage comprises tablet, discrete particles, capsule, slow releasing tablet, sustained release pellet etc.Solid carrier can be at least a material, and it can serve as thinner, flavouring agent, solubilizing agent, lubricant, suspension agent, tackiness agent, disintegrating agent and coating agent.Inert solid carrier comprises trimagnesium phosphate, Magnesium Stearate, smoothers sugar, lactose, pectin, propylene glycol, Polysorbate 80, dextrin, starch, gelatin, cellulose substances such as methylcellulose gum, Microcrystalline Cellulose, low melt point paraffin, polyoxyethylene glycol, N.F,USP MANNITOL, theobroma oil etc.Liquid dosage form comprises solvent, suspension for example injection, pulvis etc.
The amount of the active ingredient that contains in pharmaceutical composition and the unit dosage form (the present invention contains the compound of formula I) can specifically be applied according to patient's the state of an illness, the situation of diagnosis, and the amount of used compound or concentration are regulated in a wider scope.Usually, the weight range of active compound is 1%～90% (weight) of composition, and another preferred scope is 10%～70%.
Compound and pharmacy acceptable salt thereof with formula I structure of the present invention has obvious effect aspect hyperglycemia.
Embodiment
Below in conjunction with specific embodiment the present invention is described in further detail.
Embodiment 1: the preparation of intermediate III
Take intermediate III-1 as example
Figure BDA00002647154000061
In the reaction flask that stirring, condenser, thermometer are housed, add 2-(piperazine-1-yl) benzothiazole (2.19g, 0.01mol), 3-chlorine propylamine (1.2g, 0.015mol) and sodium hydroxide (7.2g, 0.18mol), DMF(30ml) dissolving, 50 ℃ of reaction 4h.Naturally cool to room temperature, filter, in filtrate, add potassium acetate (0.24g), vacuum distilling goes out about 25mL DMF, adds the dilution of 50mL water in the residue, is 4.6 with the acetic acid adjust pH, dichloromethane extraction, water layer are used the dichloromethane extraction secondary after being 9.5 with 12% ammonia solution adjust pH again, each 50mL, anhydrous sodium sulfate drying steams solvent, and obtaining yellow oil is intermediate III-1, HPLC:92%, HRMS (m/z): 263.1325.
Method with reference to embodiment 1 can conveniently prepare compound: preparation process and the result of intermediate III-2-III-10 are as shown in table 1, and the benzo five-membered heterogeneous ring compound that wherein contains piperazine is 0.01mol, and the alkyl chloride aminated compounds is 0.015mol.
Table 1
Figure BDA00002647154000071
Embodiment 2:
N-(2-(4-(benzothiazole-2-yl) piperazine-1-yl) ethyl)-3, the preparation of 5-dimethyl benzene sulfonamide (chemical compounds I-1):
Figure BDA00002647154000081
Stirring is being housed, condenser, add 2.46g(0.01mol in the reaction flask of thermometer) the intermediate III-1 that makes of embodiment 1, with the 10mL methylene dichloride it is dissolved, stir, add Anhydrous potassium carbonate 2.2g, drip 3,5-3,5-dimethylphenyl-1-SULPHURYL CHLORIDE 2.1g(0.01mol under the condition of ice bath), drip and finish, stir about 3h under room temperature, the TLC detection reaction is complete, crosses filter solid, filtrate water washing three times, each water 15mL, organic layer is fully dry with anhydrous sodium sulphate, filters, and to the greatest extent organic solvent is steamed in decompression, light yellow oil, it is chemical compounds I-1(HPLC:99.5%) that silica gel column chromatography gets white solid product.161 ℃-162.1 ℃ of fusing points, HRMS(m/z): 431.1570.
Method with reference to embodiment 2 can conveniently prepare chemical compounds I-2-I-10.Preparation process and the result of chemical compounds I-2-I-10 are as shown in table 2.Wherein the benzene sulfonyl chloride of intermediate III and replacement is 0.01mol for waiting mole.
Table 2
Figure BDA00002647154000091
Chemical compounds I-2,178 ℃-179.2 ℃ of fusing points,
Chemical compounds I-5,164.4 ℃-165.7 ℃ of fusing points,
Chemical compounds I-8,180.6 ℃-182.4 ℃ of fusing points,
Chemical compounds I-10,193.2 ℃-194.1 ℃ of fusing points.
Embodiment 3
Chemical compounds I-10 one-tenth hydrochloride: get chemical compounds I-10 white solid product 2.0g, be dissolved in the 10mL anhydrous diethyl ether.Ice-water bath is cooled to 0 ℃, and dripping 25% hydrochloric acid diethyl ether solution to pH value is 2, continues at stir about 1h under the ice-water bath.Filter, get white solid, be the hydrochloride of chemical compounds I-10.
Embodiment 4:
Chemical compounds I-5 one-tenth taurate: get chemical compounds I-5 white solid product 2.0g, be dissolved in the 15mL dehydrated alcohol.Be heated to rear the adding and the equimolar taurine of chemical compounds I-5 of refluxing, continue at the lower about 2h of stirring reaction that refluxes.React complete, under room temperature, leave standstill 24h.Filter, get the taurate that light yellow solid is chemical compounds I-5.
Embodiment 5:
Chemical compounds I-9 one-tenth vitriol: get chemical compounds I-9 white solid product 2.0g, be dissolved in the 20mL anhydrous methanol.Ice-water bath is cooled to 5 ℃, and dripping concentrated sulfuric acid solution to pH value is 3, continues at stir about 0.5h under the ice-water bath.Filter, get the vitriol that light yellow solid is chemical compounds I-9.
For the pharmaceutical composition of sulfonamides compound of the present invention is described more fully, the below provides following example of formulations, and described embodiment only is used for explanation, rather than is used for limiting the scope of the invention.Described preparation can use any active compound in the compounds of this invention, preferably uses the compound described in the embodiment 1-5.
Embodiment 6
Prepare hard gelatin capsule with following compositions:
Consumption/capsule
Chemical compounds I-2 20mg
Dry starch 200mg
Magnesium Stearate 10mg
After the mentioned component mixing, be packed in the hard gelatin capsule.
Embodiment 7
Prepare tablet with following compositions:
Figure BDA00002647154000111
Supplementary material is dry in advance, and it is for subsequent use to cross 100 mesh sieves.First with supplementary product starch, carboxymethyl starch sodium salt, Magnesium Stearate, the abundant mixing of talcum powder of recipe quantity.Bulk drug chemical compounds I-8 is added in the auxiliary material to increase progressively dilution method, and each abundant mixing of added-time 2-3 time guarantees bulk drug and the abundant mixing of auxiliary material, cross 20 mesh sieves, dry 2h in 55 ℃ of ventilated drying ovens, dried particle cross the whole grain of 16 mesh sieves, measure intermediate content, mix compressing tablet on tabletting machine.
Embodiment 8
The preparation of injection liquid:
The hydrochloride 200mg of chemical compounds I-10
Propylene glycol 100mg
Sorbyl alcohol 20mg
Distilled water 300ml
Sorbyl alcohol and propylene glycol be dissolved in make water for injection in the distilled water.The hydrochloride of getting activeconstituents and be chemical compounds I-10 joins in the water for injection that dissolves sorbyl alcohol and propylene glycol, adds medicinal basic and regulates pH value to 6.5 and make its dissolving.Add gac 10mg, whip attachment 30 minutes, carbon removal, smart filter, embedding, sterilization.
Embodiment 9
The preparation of injection lyophilized powder:
The taurate 100mg of chemical compounds I-5
Aqueous sodium hydroxide solution 5%
N.F,USP MANNITOL 30mg
The taurate of getting activeconstituents and be chemical compounds I-5 does not add water for injection 50ml, regulates pH value to 7.5 with medicinal basic and makes its dissolving.Add again N.F,USP MANNITOL, carry out autoclaving by the requirement of injection, add gac; adopt filtering with microporous membrane, filtrate is carried out packing, adopts freeze-drying; make loose block, seal, namely get the injection lyophilized powder of the taurate that contains chemical compounds I-5.
Further specify the hypoglycemic activity of the compounds of this invention below by pharmacodynamic experiment.
The oral sugar tolerance model of mouse (oral glucose tolerance test, OGTT) is measured.
1, laboratory sample:
Laboratory sample is chemical compounds I-1-chemical compounds I-10 or Walaphage.Sample is mixed with 5mgmL with 1% Xylo-Mucine -1The suspension of concentration, dosage are every 20g body weight 0.4mL, are equivalent to 100mgkg -1Dosage.
2, experimentation:
Healthy ICR mouse, male and female half and half, body weight 20g～24g meets primary standard.Animal fasting 16h gives respectively chemical compounds I-1-chemical compounds I-10, Walaphage, after the administration behind the 15min, 1.5h abdominal injection 2gkg -1Dextrose in saline solution, respectively at 0.50h after the modeling, 1.00h, 1.50h, 2.00h, 2.50h, 3.00h 3.50h and 4.00h regularly get blood with kapillary from mouse ball rear vein beard, for the first time 2h injectable dextrose monohydrate salt brine solution again behind the injectable dextrose monohydrate, centrifugation serum is with each time point serum glucose level of determination of glucose oxidase.If the blank group gives 1% Xylo-Mucine of equivalent.
The hypoglycemic activity of compound is weighed by inhibiting rate (inhibitory rate, IR%), the results are shown in Table 3.
IR%={1-[AUC (7a-7u)/AUC (model)] } * 100%, wherein, AUC is the area under curve (area under carve) of " blood sugar concentration-time " curve.
Table 3: to the mouse blood sugar restraining effect
Figure BDA00002647154000131
By above pharmacological evaluation as seen, compound of the present invention has obvious inhibition than the Walaphage of blank group, at present clinical the most normal use to hyperglycemia.
The above only is preferred implementation of the present invention; should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.

Claims (10)

1. a class sulfonamides compound is characterized in that, has the structure of following formula I:
Figure FDA00002647153900011
Wherein:
X is S or O atom;
N=1,2,3 or 4;
R 1With R 2Be hydrogen or C1-C4 alkyl at the same time or separately;
R 3, R 4With R 5Be that hydrogen, C1-C6 alkyl, C1-C4 alkoxyl group, halogen, list or many halogens replace any in C1-C4 alkyl, cyano group, phenyl, single halogenophenyl, C1-C4 alkoxyl phenyl, C1-C4 alkyl sulphonyl, the brooethyl carbonyl at the same time or separately.
2. the sulfonamides compound described in according to claim 1 is characterized in that, comprises following compound:
Figure FDA00002647153900012
Figure FDA00002647153900021
3. the preparation method of a sulfonamides compound claimed in claim 1 is characterized in that, comprises the steps:
(1) have the benzo five-membered heterogeneous ring compound that contains piperazine of general formula II and alkyl chloride aminated compounds in the presence of acid binding agent, in solvent, 0～110 ℃ of reaction response obtains having the compound of general formula III;
(2) above-mentioned compound with general formula III and the benzene sulfonyl chloride of the replacement with general formula IV are in the presence of acid binding agent, and in solvent, 0～110 ℃ of reaction obtains having the sulfonamides compound of formula I;
Wherein:
X is S or O atom;
N=1,2,3 or 4;
R 1With R 2Be hydrogen or C1-C4 alkyl at the same time or separately;
R 3, R 4With R 5Be that hydrogen, C1-C6 alkyl, C1-C4 alkoxyl group, halogen, list or many halogens replace any in C1-C4 alkyl, cyano group, phenyl, single halogenophenyl, C1-C4 alkoxyl phenyl, C1-C4 alkyl sulphonyl, the brooethyl carbonyl at the same time or separately;
Syntheti c route is expressed as follows:
Figure FDA00002647153900031
4. the preparation method of sulfonamides compound according to claim 3, it is characterized in that, described alkyl chloride aminated compounds is haloalkyl amine, described acid binding agent is triethylamine, pyridine, salt of wormwood, yellow soda ash, sodium bicarbonate, saleratus, sodium hydroxide or potassium hydroxide, and described solvent is methylene dichloride, trichloromethane, acetonitrile, tetrahydrofuran (THF), DMF or toluene.
5. class sulfonamides compound pharmacy acceptable salt claimed in claim 1 is characterized in that, this pharmacy acceptable salt is compound and mineral acid or the organic acid institute salify of general formula I.
6. the preparation method of class sulfonamides compound pharmacy acceptable salt claimed in claim 5, it is characterized in that, comprise the steps: claim 1 or 2 described sulfonamides compounds are dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, drip mineral acid or organic acid, make pharmacy acceptable salt.
7. the preparation method of sulfonamides compound pharmacy acceptable salt according to claim 6, it is characterized in that, claim 1 or 2 described sulfonamides compounds are dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, under ice-water bath, drip the salt acid ether to pH=2, make hydrochloride; Or claim 1 or 2 described sulfonamides compounds are dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, add and described claim 1 or the equimolar gluconic acid of 2 described sulfonamides compounds, heated and stirred gets gluconate; Perhaps claim 1 or 2 described sulfonamides compounds are dissolved in a kind of among ether, DMF, acetone, methyl alcohol, ethanol, ethyl acetate or the DMSO, under ice-water bath, drip the vitriol oil to pH=3, make vitriol.
8. pharmaceutical composition with hypoglycemic activity, it comprises the compound that contains formula I described in the claim 1 or 2 for the treatment of significant quantity or contains pharmacy acceptable salt claimed in claim 5.
9. the compound that contains formula I described in the claim 1 or 2 is in the application aspect hypoglycemic drug.
10. the pharmacy acceptable salt of the compound that contains formula I claimed in claim 5 is in the application aspect hypoglycemic drug.
CN201210575394.4A 2012-12-25 2012-12-25 Sulfonamide compound and preparation method as well as application thereof Expired - Fee Related CN103012314B (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109438388A (en) * 2018-12-04 2019-03-08 天津商业大学 Novel crystal forms have blood sugar reducing function compound and preparation method and the composition containing it
CN109651349A (en) * 2019-01-07 2019-04-19 天津商业大学 The novel crystal forms and preparation method and application of sulfonamides compound

Citations (3)

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Publication number Priority date Publication date Assignee Title
US4761287A (en) * 1984-05-03 1988-08-02 Technology Unlimited, Inc. Diabetes control by serotonin
WO2000056712A1 (en) * 1999-03-23 2000-09-28 Smithkline Beecham Plc Sulfonamide derivatives as 5-ht7 receptor antagonists
CN1756551A (en) * 2003-01-31 2006-04-05 普雷迪克医药品控股公司 New arylpiperazinyl compounds

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4761287A (en) * 1984-05-03 1988-08-02 Technology Unlimited, Inc. Diabetes control by serotonin
WO2000056712A1 (en) * 1999-03-23 2000-09-28 Smithkline Beecham Plc Sulfonamide derivatives as 5-ht7 receptor antagonists
CN1756551A (en) * 2003-01-31 2006-04-05 普雷迪克医药品控股公司 New arylpiperazinyl compounds

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109438388A (en) * 2018-12-04 2019-03-08 天津商业大学 Novel crystal forms have blood sugar reducing function compound and preparation method and the composition containing it
CN109438388B (en) * 2018-12-04 2022-05-10 天津商业大学 Crystal form of compound with hypoglycemic effect, preparation method and composition containing crystal form
CN109651349A (en) * 2019-01-07 2019-04-19 天津商业大学 The novel crystal forms and preparation method and application of sulfonamides compound
CN109651349B (en) * 2019-01-07 2022-01-07 天津商业大学 Novel crystal form of sulfonamide compound, preparation method and application

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