CN102030673A - New crystal form of agomelatine and preparation method thereof - Google Patents
New crystal form of agomelatine and preparation method thereof Download PDFInfo
- Publication number
- CN102030673A CN102030673A CN2010105731503A CN201010573150A CN102030673A CN 102030673 A CN102030673 A CN 102030673A CN 2010105731503 A CN2010105731503 A CN 2010105731503A CN 201010573150 A CN201010573150 A CN 201010573150A CN 102030673 A CN102030673 A CN 102030673A
- Authority
- CN
- China
- Prior art keywords
- agomelatine
- preparation
- crystal
- tetrahydrofuran
- new crystal
- 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.)
- Granted
Links
Images
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a new crystal form of agomelatine and a preparation method thereof, belonging to the technical field of chemical synthesis of drugs. The invention discloses a new crystal form of the agomelatine which is a drug for treating depression, and has a single absorption peak near 108 DEGC through differential scanning thermoanalysis. The invention further discloses a method for preparing the new crystal form of the agomelatine in tetrahydrofuran.
Description
Technical field
The invention belongs to the pharmaceutical chemistry synthesis technical field, relate to a kind of new crystal of thymoleptic Agomelatine and preparation method.
Background technology
Agomelatine (Agomelatine) is the thymoleptic of first rake of French Servier company exploitation to the melatonin hormone, also is simultaneously as MT1 and MT2 melatonin receptor agonist and 5-HT
2cThe first thymoleptic of antagonist.Compare with serotonin NRI (SNRI) thymoleptic with traditional selective serotonin reuptake inhibitor (SSRI), has more remarkable antidepressant curative effect, can make the serious disorderly biorhythm of patients with depression recover normal again, and in the major depressive disorder patient, the antidepressant curative effect of Agomelatine is better than the fluoxetine of SSRI class.Vast amount of clinical confirms, Agomelatine treatment dysthymia disorders good effect, rapid-action, improve the anxiety symptom of following simultaneously; Can improve the people that sleep, the alertness on daytime is not had influence; Security and better tolerance, especially little to the influence of sexual function, thymoleptic had more advantage more in the past.
Agomelatine, chemical name are n-[2-(7-methoxyl group-1-naphthyl) ethyl] ethanamide, its structural formula is as follows:
Have many pieces of bibliographical informations about Agomelatine: having described with 7-methoxyl group-1-Tetralone an intermediate of Sertraline among the European patent specification EP0447285A is the method for starting raw material through the synthetic Agomelatine of 7 steps reaction.Novel method with the synthetic Agomelatine of 7-methyl isophthalic acid-naphthols has been described among the EP2151428A.Acta Cryst, 1994, C50 is described in detail crystal formation I in 907～910.The method that Chinese patent specification sheets CN1680284 has put down in writing with ethanol/water mixed solution recrystallization prepares the Agomelatine crystal form II.Chinese patent specification sheets CN1907959 has put down in writing the preparation of the new crystal III of Agomelatine, both Agomelatine is slowly cooled off until crystallization behind the heating fine melt down at 110 ℃.CN1907957 has described Agomelatine has been dissolved back cooling rapidly between 50～70 ℃ fully, and keeps the method that about 5h prepares form IV at 70 ℃.Chinese patent specification sheets CN1907958 has described the method for preparing crystal form V.Put down in writing the preparation method of crystal form V I among the CN101429134.
The inventor has found to be different from the Agomelatine new crystal of existing bibliographical information in research process, obtained X-ray powder diffraction spectrum.This crystal formation purity height, good stability has superiority in explained hereafter, be fit to preparation technical process and long-term deposit.
Summary of the invention
One object of the present invention is to provide a kind of Agomelatine new crystal, and is stable with the quality of the pharmaceutical preparations of its preparation, favorable reproducibility.
Another object of the present invention has provided the preparation method of Agomelatine new crystal.
A kind of Agomelatine crystal formation, the analysis of difference formula scanning calorimeter has single absorption peak near 108 ℃, and this crystal form X-ray powder diffraction feature is expressed as follows with 2 θ diffraction angle, spacing D and relative intensity:
The preparation method of Agomelatine new crystal of the present invention is characterized in that Agomelatine is dissolved in the tetrahydrofuran (THF), drips water in system, filters drying.
In the above-mentioned preparation process, between 10～20 ℃, drip the water best results.Owing to make in its crystallization precipitation process adding water to the Agomelatine tetrahydrofuran solution, solution system can heat release, occurs mixed crystal phenomenon this moment easily, and it is necessary therefore solution being cooled to 10～20 ℃.
In the above-mentioned preparation process, the consumption of tetrahydrofuran (THF) is preferably 2～4ml with respect to the 1g Agomelatine.Experimental studies have found that when the consumption of tetrahydrofuran (THF) was 2～4ml with respect to the 1g Agomelatine, the Agomelatine tetrahydrofuran solution can form saturated solution at 10～20 ℃.
In the above-mentioned preparation process, the consumption of water is preferably 8～10ml with respect to the 1ml tetrahydrofuran (THF).Experimental studies have found that when the consumption of water was 8～10ml with respect to the 1ml tetrahydrofuran (THF), the tetrahydrofuran (THF) water mixed solution did not almost have solvability to Agomelatine.
No matter which kind of crystal habit the Agomelatine before the dissolving is, whether is solvate, all obtain this Agomelatine new crystal by above-mentioned preparation process.
Agomelatine crystal disclosed by the invention has and the identical purposes of known Agomelatine compound itself.Mouse test shows that after the Agomelatine new crystal mouse of the present invention administration, MT content is apparently higher than control group in the blood plasma.
New crystal has the effect of melatonin receptors agonist, it also is serotonin 2C receptor antagonist, can be used for that treatment is depressed, severe is depressed, seasonal affective disorder, somnopathy, cardiovascular pathology and physiological clock adjusting etc., be the medicine that can be used for making the treatment dysthymia disorders.
Description of drawings
Fig. 1 is an Agomelatine crystal X-ray powder diffraction.
Fig. 2 is an Agomelatine crystal DSC endothermic transition collection of illustrative plates.
Embodiment
100 gram Agomelatines are joined in 200 milliliters of tetrahydrofuran (THF)s the heated and stirred dissolving.Tetrahydrofuran solution with the gained Agomelatine after the dissolving is cooled between 10 ℃～20 ℃, stirs slowly to drip 1600 ml waters down, maintains the temperature between 10 ℃～20 ℃.Dropwise, filter crystal, vacuum-drying got Agomelatine crystal 99.1 grams, yield: 99.1% in 12 hours.
Embodiment 2
100 gram Agomelatines are joined in 300 milliliters of tetrahydrofuran (THF)s the heated and stirred dissolving.Tetrahydrofuran solution with the gained Agomelatine after the dissolving is cooled between 10 ℃～20 ℃, stirs slowly to drip 2400 ml waters down, maintains the temperature between 10 ℃～20 ℃.Dropwise, filter crystal, vacuum-drying got Agomelatine crystal 99.1 grams, yield: 99.1% in 12 hours.
100 gram Agomelatines are joined in 400 milliliters of tetrahydrofuran (THF)s the heated and stirred dissolving.Tetrahydrofuran solution with the gained Agomelatine after the dissolving is cooled between 10 ℃～20 ℃, stirs slowly to drip 4000 ml waters down, maintains the temperature between 10 ℃～20 ℃.Dropwise, filter crystal, vacuum-drying got Agomelatine crystal 99.0 grams, yield: 99.0% in 12 hours.
Embodiment 4
100 gram Agomelatines are joined in 300 milliliters of tetrahydrofuran (THF)s the heated and stirred dissolving.Tetrahydrofuran solution with the gained Agomelatine after the dissolving is cooled between 10 ℃～20 ℃, stirs slowly to drip 2700 ml waters down, maintains the temperature between 10 ℃～20 ℃.Dropwise, filter crystal, vacuum-drying got Agomelatine crystal 99.1 grams, yield: 99.1% in 12 hours.
Above embodiment only is used for further explaining the present invention, is not used in the restriction that also should not be understood that inventing in the claim.
Claims (7)
1. Agomelatine new crystal, its X-ray powder diffraction feature is expressed as follows with 2 θ diffraction angle, spacing D and relative intensity:
2. the new crystal of the described Agomelatine of claim 1, its difference formula scanning calorimeter analysis has single absorption peak near 108 ℃.
3. claim 1 or the new crystalline preparation method of 2 described Agomelatines is characterized in that Agomelatine is dissolved in the tetrahydrofuran (THF), drip water in system, filter drying.
4. the described preparation method of claim 3 is characterized in that dripping water between 10～20 ℃.
5. the described preparation method of claim 3, the consumption that it is characterized in that water is 8～10ml with respect to the 1ml tetrahydrofuran (THF).
6. the described preparation method of claim 3, the consumption that it is characterized in that tetrahydrofuran (THF) is 2～4ml with respect to the 1g Agomelatine.
7. claim 1 or the 3 defined Agomelatine crystal application in the medicine of preparation treatment dysthymia disorders.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010573150.3A CN102030673B (en) | 2010-11-24 | 2010-11-24 | New crystal form of agomelatine and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010573150.3A CN102030673B (en) | 2010-11-24 | 2010-11-24 | New crystal form of agomelatine and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102030673A true CN102030673A (en) | 2011-04-27 |
| CN102030673B CN102030673B (en) | 2014-04-23 |
Family
ID=43884186
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010573150.3A Expired - Fee Related CN102030673B (en) | 2010-11-24 | 2010-11-24 | New crystal form of agomelatine and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102030673B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102557979A (en) * | 2010-12-16 | 2012-07-11 | 北大方正集团有限公司 | Agomelatine crystal form, as well as preparation method, application and medicinal composition thereof |
| EP2556824A1 (en) | 2011-08-10 | 2013-02-13 | Les Laboratoires Servier | Solid pharmaceutical composition for buccal administration of agomelatine |
| CN103130673A (en) * | 2011-11-28 | 2013-06-05 | 重庆医药工业研究院有限责任公司 | Preparation method of agomelatine crystal type I |
| CN103360275A (en) * | 2012-03-30 | 2013-10-23 | 上海希迈医药科技有限公司 | Method for preparing agomelatine I-type crystal |
| WO2014122405A1 (en) | 2013-02-08 | 2014-08-14 | Les Laboratoires Servier | Solid pharmaceutical composition for oral delivery of agomelatine |
| EP3075724A1 (en) | 2015-03-31 | 2016-10-05 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Solid form of agomelatine |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1680284A (en) * | 2004-02-13 | 2005-10-12 | 瑟维尔实验室 | New process for the synthesis and new crystalline form of agomelatine and pharmaceutical compositions containing it |
| CN101735091A (en) * | 2009-12-30 | 2010-06-16 | 北京德众万全药物技术开发有限公司 | Preparation method of Agomelatine |
| CN101759591A (en) * | 2009-07-11 | 2010-06-30 | 浙江华海药业股份有限公司 | Preparing method of N-[2-(7- anisyl-1- naphthyl) ethide] acetamide |
| CN101774937A (en) * | 2010-02-05 | 2010-07-14 | 天津市汉康医药生物技术有限公司 | N-[2-(7-methoxyl-1-naphthyl)ethyl]acetamide and compound thereof |
| CN102050755A (en) * | 2009-10-29 | 2011-05-11 | 重庆医药工业研究院有限责任公司 | Novel agomelatine crystal forms and preparation methods of agomelatine crystal forms |
-
2010
- 2010-11-24 CN CN201010573150.3A patent/CN102030673B/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1680284A (en) * | 2004-02-13 | 2005-10-12 | 瑟维尔实验室 | New process for the synthesis and new crystalline form of agomelatine and pharmaceutical compositions containing it |
| CN101759591A (en) * | 2009-07-11 | 2010-06-30 | 浙江华海药业股份有限公司 | Preparing method of N-[2-(7- anisyl-1- naphthyl) ethide] acetamide |
| CN102050755A (en) * | 2009-10-29 | 2011-05-11 | 重庆医药工业研究院有限责任公司 | Novel agomelatine crystal forms and preparation methods of agomelatine crystal forms |
| CN101735091A (en) * | 2009-12-30 | 2010-06-16 | 北京德众万全药物技术开发有限公司 | Preparation method of Agomelatine |
| CN101774937A (en) * | 2010-02-05 | 2010-07-14 | 天津市汉康医药生物技术有限公司 | N-[2-(7-methoxyl-1-naphthyl)ethyl]acetamide and compound thereof |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102557979A (en) * | 2010-12-16 | 2012-07-11 | 北大方正集团有限公司 | Agomelatine crystal form, as well as preparation method, application and medicinal composition thereof |
| CN102557979B (en) * | 2010-12-16 | 2014-11-26 | 北大方正集团有限公司 | Agomelatine crystal form, as well as preparation method, application and medicinal composition thereof |
| EP2556824A1 (en) | 2011-08-10 | 2013-02-13 | Les Laboratoires Servier | Solid pharmaceutical composition for buccal administration of agomelatine |
| WO2013021139A1 (en) | 2011-08-10 | 2013-02-14 | Les Laboratoires Servier | Solid pharmaceutical composition for orally delivering agomelatine |
| CN103130673A (en) * | 2011-11-28 | 2013-06-05 | 重庆医药工业研究院有限责任公司 | Preparation method of agomelatine crystal type I |
| CN103130673B (en) * | 2011-11-28 | 2017-05-03 | 重庆医药工业研究院有限责任公司 | Preparation method of agomelatine crystal type I |
| CN103360275A (en) * | 2012-03-30 | 2013-10-23 | 上海希迈医药科技有限公司 | Method for preparing agomelatine I-type crystal |
| CN103360275B (en) * | 2012-03-30 | 2015-04-22 | 上海创诺制药有限公司 | Method for preparing agomelatine I-type crystal |
| WO2014122405A1 (en) | 2013-02-08 | 2014-08-14 | Les Laboratoires Servier | Solid pharmaceutical composition for oral delivery of agomelatine |
| EP3075724A1 (en) | 2015-03-31 | 2016-10-05 | F.I.S.- Fabbrica Italiana Sintetici S.p.A. | Solid form of agomelatine |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102030673B (en) | 2014-04-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102030673B (en) | New crystal form of agomelatine and preparation method thereof | |
| EP2474522B1 (en) | Agomelatine and pharmaceutical compositions thereof | |
| CN102190616B (en) | A kind of deuterated synthesis of ω-diphenyl urea and the Method and process of production | |
| CN103974949B (en) | A kind of I type crystallization of 2-maleate of tyrosine kinase inhibitor and preparation method | |
| EP3248983B1 (en) | Crystal form a of obeticholic acid and preparation method therefor | |
| CN109996540A (en) | (R) solvate forms of -2- amino -3- Phenylpropylamino formic acid esters | |
| RU2013158816A (en) | NEW Agomelatine Co-crystals, Method for Their Production and Pharmaceutical Compositions Which Contain Them | |
| WO2011006387A1 (en) | Process for preparing agomelatine, crystals of agomelatine and preparing process thereof | |
| CN101704763A (en) | Preparation method of agomelatine I type crystal | |
| CN102001960A (en) | Method for preparing agomelatine | |
| CN101955440A (en) | Novel crystal form of agomelatine and preparation method thereof | |
| CN101781225A (en) | Preparation method of agomelatine crystal form A | |
| TW201136897A (en) | New crystalline form of a cyclopropyl benzamide derivative | |
| CA3159749A1 (en) | Salts and forms of an estrogen receptor modulator | |
| CN101723844A (en) | Agomelatine crystal form B, preparation method thereof and medicinal composition containing same | |
| CN102452951B (en) | Agomelatine and pharmaceutical composition thereof | |
| WO2012126385A1 (en) | New crystal form vii of agomelatine, preparation method and use thereof and pharmaceutical composition containing same | |
| WO2021196949A1 (en) | Crystalline form a of glp-1 receptor agonist and preparation method therefor | |
| WO2012126386A1 (en) | Mixed crystal agomelatine (form-viii), preparation method and use thereof and pharmaceutical composition containing same | |
| CN109476584B (en) | N- (2- (substitution-naphthalene -1- base) ethyl) substituted amide class compound, its preparation and application thereof | |
| CN102432490A (en) | Agomelatine crystal form D and preparation method thereof | |
| CN109516991A (en) | A kind of citric acid tropsch imatinib crystal-form compound and preparation method thereof | |
| WO2014187229A1 (en) | Preparation method for agomelatine crystal form i | |
| CN111606816A (en) | Dezocine crystal form and preparation method thereof | |
| CN113527275A (en) | SKLB1039 compound and preparation method 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 | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140423 Termination date: 20191124 |