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1. 发明授权

US08779005B2 Salts of desvenlafaxine and a method of their preparation 有权
标题翻译：去甲文拉法辛盐及其制备方法
公开(公告)号：US08779005B2
公开(公告)日：2014-07-15
申请号：US13146467
申请日：2010-02-03
申请人： Ludek Ridvan , Petr Hruby , Stanislav Radl , Hana Brusova , Lukas Krejcik , Tomas Pekarek , Natalia Csokova , Anna Zerzanova
发明人： Ludek Ridvan , Petr Hruby , Stanislav Radl , Hana Brusova , Lukas Krejcik , Tomas Pekarek , Natalia Csokova , Anna Zerzanova
IPC分类号： A61K31/205 , C07C215/52
CPC分类号： A61K31/205 , C07B2200/13 , C07C51/412 , C07C55/07 , C07C213/08 , C07C213/10 , C07C215/52 , C07C215/64 , C07C2601/14
摘要： The invention deals with new salts of the desvenlafaxine base of formula (I) with oxalic acid, the new salts being the hydrogen oxalate of formula (II) in the proportion of desvenlafaxine:oxalic acid of 1:1 and hemioxalate of formula (III) in the proportion of desvenlafaxine:oxalic acid of 2:1.
摘要翻译：本发明涉及式（I）的去甲文拉法辛碱与草酸的新盐，新盐是式（II）的草酸氢盐，其中去甲文拉法辛：草酸为1:1，式（III）的次氯酸盐以去甲文拉法辛：草酸为2：1的比例。

2. 发明授权

US08207356B2 Method for the preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine hydrochloride (duloxetine) 失效
标题翻译：制备（S）-N-甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺盐酸盐（度洛西汀）的方法
公开(公告)号：US08207356B2
公开(公告)日：2012-06-26
申请号：US13253441
申请日：2011-10-05
申请人： Ludek Ridvan , Kamal Jarrah , Josef Cinibulk , Monika Zatopkova , Lukas Placek
发明人： Ludek Ridvan , Kamal Jarrah , Josef Cinibulk , Monika Zatopkova , Lukas Placek
IPC分类号： C07D333/20
CPC分类号： C07D333/20
摘要： A method for the preparation of a duloxetine hydrochloride salt from a duloxetine base, comprising the steps of: reacting duloxetine base with concentrated hydrochloric acid in ethylmethylketone; and crystallizing duloxetine hydrochloride salt from said concentrated hydrochloric acid in ethylmethylketone.
摘要翻译：一种从度洛西汀碱制备度洛西汀盐酸盐的方法，包括以下步骤：将度洛西汀碱与浓盐酸在乙基甲基酮中反应; 并从所述浓盐酸在乙基甲基酮中结晶度洛西汀盐酸盐。

3. 发明申请

US20120041227A1 NEW SALTS OF DESVENLAFAXINE AND A METHOD OF THEIR PREPARATION 有权
标题翻译：维生素D的新盐及其制备方法
公开(公告)号：US20120041227A1
公开(公告)日：2012-02-16
申请号：US13146467
申请日：2010-02-03
申请人： Ludek Ridvan , Petr Hruby , Stanislav Radl , Hana Brusova , Lukas Krejcik , Tomas Pekarek , Natalia Csokova , Anna Zerzanova
发明人： Ludek Ridvan , Petr Hruby , Stanislav Radl , Hana Brusova , Lukas Krejcik , Tomas Pekarek , Natalia Csokova , Anna Zerzanova
IPC分类号： C07C229/34
CPC分类号： A61K31/205 , C07B2200/13 , C07C51/412 , C07C55/07 , C07C213/08 , C07C213/10 , C07C215/52 , C07C215/64 , C07C2601/14
摘要： The invention deals with new salts of the desvenlafaxine base of formula (I) with oxalic acid, the new salts being the hydrogen oxalate of formula (II) in the proportion of desvenlafaxine:oxalic acid of 1:1 and hemioxalate of formula (III) in the proportion of desvenlafaxine:oxalic acid of 2:1.
摘要翻译：本发明涉及式（I）的去甲文拉法辛碱与草酸的新盐，新盐是式（II）的草酸氢盐，其中去甲文拉法辛：草酸为1:1，式（III）的次氯酸盐以去甲文拉法辛：草酸为2：1的比例。

4. 发明申请

US20100105919A1 METHOD FOR THE PREPARATION OF ZOLMITRIPTAN 有权
标题翻译：制备ZOLMITRIPTAN的方法
公开(公告)号：US20100105919A1
公开(公告)日：2010-04-29
申请号：US12526958
申请日：2008-02-25
申请人： Michal Voslar , Monika Zatopkova , Ludek Ridvan , Tomas Pekarek
发明人： Michal Voslar , Monika Zatopkova , Ludek Ridvan , Tomas Pekarek
IPC分类号： C07D263/04
CPC分类号： C07D413/06
摘要： In the preparation of zolmitriptan of formula III the reduction of the diazonium salt to (5)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one of formula IV is performed in a more concentrated mixture and by the effect on an alkali metal disulphite, preferably sodium disulphite. A zolmitriptan toluene solvate, characterized by a toluene content of 9 to 14% by weight according to the gas chromatography determination and by a maximum of the corresponding mass loss at temperatures of about 111° C. in the gravimetric analysis record. A zolmitriptan toluene solvate, showing strong Raman bands at the wave numbers of 1443 and 1354 cm−1, characteristic for the crystal lattice of zolmitriptan with built-in toluene, and further marked bands at 1004 and 786 cm−1, characteristic for toluene.
摘要翻译：在式III的佐米曲坦的制备中，将重氮盐还原成式IV的（5）-4-（4-肼基苄基）-1,3-恶唑烷-2-酮，以更浓缩的混合物和效果在碱金属亚硫酸盐上，优选二亚硫酸钠。唑来曲坦甲苯溶剂化物，其特征在于根据气相色谱测定的甲苯含量为9至14重量％，并且在重量分析记录中在约111℃的温度下达到最大的相应质量损失。唑来曲坦甲苯溶剂化物，在1443和1354厘米-1的波数显示强拉曼带，具有内置甲苯的佐米曲坦的晶格特征，以及在1004和786厘米-1处的进一步标记的带，特征在于甲苯。

5. 发明授权

US07709662B2 Method of manufacturing (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine hydrochloride (duloxetine) 有权
标题翻译：制备（S）-N-甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺盐酸盐（度洛西汀）的方法
公开(公告)号：US07709662B2
公开(公告)日：2010-05-04
申请号：US11718042
申请日：2005-10-21
申请人： Ludek Ridvan , Petr Hruby , Lukas Placek , Miroslav Kuchar
发明人： Ludek Ridvan , Petr Hruby , Lukas Placek , Miroslav Kuchar
IPC分类号： C07D333/12
CPC分类号： C07D333/20
摘要： A method of preparation of (S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (I) or its pharmaceutically acceptable salt, in which (RS)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (III) is reacted with an optically active acid, after which a crystallization is made of that diastereoisomer which yields, by reaction with an inorganic or organic base, (S)-N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (S)-III, which is then demethylated using alkylchloroformates, followed by a hydrolysis and optional conversion of the compound of formula (I) to its salt.
摘要翻译：制备式（I）的（S）-N-甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺或其药学上可接受的盐的方法，其中（RS）-N，使式（III）的2-（3-甲氧基）-3-（1-萘氧基）-3-（2-噻吩基）丙胺与光学活性酸反应，然后通过与无机或有机物反应产生非对映异构体，碱，（S）-N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺，然后使用氯甲酸烷基酯脱甲基，然后进行水解和任选的转化的式（I）化合物与其盐反应。

6. 发明申请

US20090143600A1 METHOD OF MANUFACTURING (S)-N-METHYL-3-(1-NAPHTHYLOXY)-3-(2-THIENYL)PROPYLAMINE HYDROCHLORIDE (DULOXETINE) 有权
标题翻译：制备（S）-N-甲基-3-（1-萘基）-3-（2-苯乙基）丙酰胺氢氯化物（DULOXETINE）的方法
公开(公告)号：US20090143600A1
公开(公告)日：2009-06-04
申请号：US11718042
申请日：2005-10-21
申请人： Ludek Ridvan , Petr Hruby , Lukas Placek , Miroslav Kuchar
发明人： Ludek Ridvan , Petr Hruby , Lukas Placek , Miroslav Kuchar
IPC分类号： C07D333/20
CPC分类号： C07D333/20
摘要： A method of preparation of (S)—N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (I) or its pharmaceutically acceptable salt, in which (RS)—N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (III) is reacted with an optically active acid, after which a crystallization is made of that diastereoisomer which yields, by reaction with an inorganic or organic base, (S)—N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine of formula (S)-III, which is then demethylated using alkylchloroformates, followed by a hydrolysis and optional conversion of the compound of formula (I) to its salt.
摘要翻译：制备式（I）的（S）-N-甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺或其药学上可接受的盐的方法，其中（RS）-N，使式（III）的2-（3-甲氧基）-3-（1-萘氧基）-3-（2-噻吩基）丙胺与光学活性酸反应，然后通过与无机或有机物反应产生非对映异构体，碱，（S）-N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺，然后使用氯甲酸烷基酯脱甲基，然后进行水解和任选的转化的式（I）化合物与其盐反应。

7. 发明申请

US20080293952A1 Method for the Preparation of (S)-N-Methyl-3-(1-Naphthyloxy)-3-(2-Thienyl)Propylamine Hydrochloride (Duloxetine) 失效
标题翻译：（S）-N-甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺盐酸盐（度洛西汀）的制备方法
公开(公告)号：US20080293952A1
公开(公告)日：2008-11-27
申请号：US12159905
申请日：2006-12-22
申请人： Ludek Ridvan , Kamal Jarrah , Josef Cinibulk , Monika Zatopkova , Lukas Placek
发明人： Ludek Ridvan , Kamal Jarrah , Josef Cinibulk , Monika Zatopkova , Lukas Placek
IPC分类号： C07D333/20
CPC分类号： C07D333/20
摘要： A method of preparation of (S)—N-methyl-3-(1-naphthyloxy)-3-(2-mienyl)propylamine of Formula (I) and its pharmaceutically acceptable salts, comprising a) reaction of (RS)—N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine with optically active D-tartaric acid or an acid salt derived from D-tartaric acid forming a mixture of diastereoisomeric salts of N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine and D-tartaric acid (2:1), b) isolation of the salt (S)—N,N-dimethyl-3-(naphthyloxy)-3-(2-thienyl)propylamine/D-tartrate (2:1) from the mixture of diastereoisomeric salts in an organic solvent, water or a mixture thereof and release of (S)—N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by action of an inorganic or organic base, c) demethylation of (S)—N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine by action of an alkylchloroformate of formula ClCOOR (R=C1-C5 alkyl, or C6-C12 aryl or alkylraryl), especially phenyl, ethyl or methyl chloroformate, and d) hydrolytic release of the duloxetine base of formula I and optionally conversion of the base to a salt with the respective acid, or salt of a weak base.
摘要翻译：制备式（I）的（S）-N-甲基-3-（1-萘氧基）-3-（2-甲基）丙胺及其药学上可接受的盐的方法，其包括a）（RS）-N ，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺与光学活性D-酒石酸或衍生自D-酒石酸的酸盐形成N，N-二甲基甲酰胺的非对映异构体盐 -3-（1-萘氧基）-3-（2-噻吩基）丙胺和D-酒石酸（2:1），b）分离盐（S）-N，N-二甲基-3-（萘氧基）在有机溶剂，水或其混合物中的非对映异构体盐的混合物中的3-（2-噻吩基）丙胺/ D-酒石酸盐（2:1）和（S）-N，N-二甲基-3-（1 （S）-N，N-二甲基-3-（1-萘氧基）-3-（2-噻吩基）丙胺的无甲基或有机碱的脱甲基化，c）（R = C1-C5烷基或C6-C12芳基或烷基芳基）的氯甲酸烷基酯，特别是苯甲基，乙基或甲基氯甲酸酯的作用，和d）水解释放式I的度洛西汀碱，并任选地将碱与相应的酸或弱碱的盐转化成盐。

8. 发明申请

US20070117964A1 Noncovalent functionalization of nanotubes 审中-公开
公开(公告)号：US20070117964A1
公开(公告)日：2007-05-24
申请号：US11653364
申请日：2007-01-16
申请人： J. Stoddart , Alexander Star , Yi Liu , Ludek Ridvan
发明人： J. Stoddart , Alexander Star , Yi Liu , Ludek Ridvan
IPC分类号： C08G75/32
CPC分类号： B82Y30/00 , C08G61/02 , C08G61/10
摘要： Nanotubes are treated with poly{(5-alkoxy-m-phenylenevinylene)-co-[(2,5-dioctyloxy-p-phenylene)vinylene]} (PAmPV) polymers and derivatives thereof to provide noncovalent functionalization of the nanotubes which increases solubility and enhances other properties.

9. 发明申请

US20140051887A1 PHARMACEUTICALLY ACCEPTABLE COCRYSTALS OF N-[2-(7-METHOXYL-1-NAPHTYL)ETHYL]ACETAMIDE AND METHODS OF THEIR PREPARATION 有权
标题翻译： N- [2-（7-甲氧基-1-萘基）乙基]乙酰胺的药学上可接受的结晶及其制备方法
公开(公告)号：US20140051887A1
公开(公告)日：2014-02-20
申请号：US14114211
申请日：2012-04-25
申请人： Gary James Miller , Ludek Ridvan , Jindrich Richter , Ondrej Dammer , Tomas Chvojka , Tomas Pekarek , Winfried Heyse , Norbert Nagel
发明人： Gary James Miller , Ludek Ridvan , Jindrich Richter , Ondrej Dammer , Tomas Chvojka , Tomas Pekarek , Winfried Heyse , Norbert Nagel
IPC分类号： C07C233/25 , C07C231/22
CPC分类号： C07C233/25 , C07B2200/13 , C07C57/145 , C07C59/265 , C07C231/22 , C07C233/18 , C07C309/29
摘要： The present invention relates to novel solid forms of agomelatine (I), specifically novel phaamaceutically acceptable cocrystals thereof, as well as to methods of preparing them. Three pharmaceutically acceptable cocrystals of (I) that have physico-chemical properties acceptable for pharmaceutical development were obtained.
摘要翻译：本发明涉及agomelatine（I）的新型固体形式，特别是新颖的药物可接受的共晶体，以及其制备方法。获得具有药物开发可接受的物理化学性质的（I）的三种药学上可接受的共晶体。

10. 发明授权

US08143417B2 Method for the preparation of zolmitriptan 有权
标题翻译：制备佐米曲坦的方法
公开(公告)号：US08143417B2
公开(公告)日：2012-03-27
申请号：US12526958
申请日：2008-02-25
申请人： Michal Voslar , Monika Zatopkova , Ludek Ridvan , Tomas Pekarek
发明人： Michal Voslar , Monika Zatopkova , Ludek Ridvan , Tomas Pekarek
IPC分类号： C07D263/04
CPC分类号： C07D413/06
摘要： In the preparation of zolmitriptan of formula III the reduction of the diazonium salt to (5)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one of formula IV is performed in a more concentrated mixture and by the effect on an alkali metal disulphite, preferably sodium disulphite. A zolmitriptan toluene solvate, characterized by a toluene content of 9 to 14% by weight according to the gas chromatography determination and by a maximum of the corresponding mass loss at temperatures of about 111° C. in the gravimetric analysis record. A zolmitriptan toluene solvate, showing strong Raman bands at the wave numbers of 1443 and 1354 cm−1, characteristic for the crystal lattice of zolmitriptan with built-in toluene, and further marked bands at 1004 and 786 cm−1, characteristic for toluene.
摘要翻译：在式III的佐米曲坦的制备中，将重氮盐还原成式IV的（5）-4-（4-肼基苄基）-1,3-恶唑烷-2-酮，以更浓缩的混合物和效果在碱金属亚硫酸盐上，优选二亚硫酸钠。唑来曲坦甲苯溶剂化物，其特征在于根据气相色谱测定的甲苯含量为9至14重量％，并且在重量分析记录中在约111℃的温度下达到最大的相应质量损失。唑来曲坦甲苯溶剂化物，在1443和1354cm -1的波数显示强拉曼带，具有内置甲苯的佐米曲坦的晶格特征，以及在1004和786cm -1处的进一步标记的带，其特征在于甲苯。

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