公开(公告)号：EP1448197A1

公开(公告)日：2004-08-25

申请号：EP02780186.9

申请日：2002-11-21

申请人： Synthon B.V.

发明人： ETTEMA, Gerrit, Jan, Bouke ,  HOORN, Hans, Jan ,  LEMMENS, Jacobus, Maria

IPC分类号： A61K31/4422 ,  C07D211/90 ,  A61P9/12 ,  A61P9/10

CPC分类号： C07D211/90

摘要： The present invention is based on the discovery that additional forms of amlodipine besylate exist beyond the single known form of the prior art. The invention also relates to anovel process for making various amlodipine besylate form. The novel amlodipine besylate forms include crystalline hydrates and anhydrates as wellas amorphous forms.

公开(公告)号：EP1318986A1

公开(公告)日：2003-06-18

申请号：EP01979066.6

申请日：2001-09-14

申请人： Synthon B.V.

发明人： POSPISILIK, Karel ,  HOORN, Hans, Jan ,  PETERS, Theodorus, Hendricus, Antonius ,  LEMMENS, Jacobus, Maria

IPC分类号： C07D277/82

CPC分类号： C07D277/82 ,  C07B2200/07

摘要： A new process to obtain pramipexole and related products is described. The process involves the reaction of new compounds of formula (6), wherein R is hydrogen or acyl group, R3 and R4 are either the same and each of them represents an alkoxy group of 1-4 carbons or they together form a C2-C5 alkylenedioxy group or an oxo-group, with an alkylamine in the presence of a reducing agent or a hydrogen gas with hydrogenation catalyst. A process to obtain new compounds of formula (6) is also described.

摘要翻译： 描述了一种获得普拉克索及相关产品的新工艺。 该方法涉及式（6）的新化合物的反应，其中R为氢或酰基，R 3和R 4相同并且它们中的每一个表示1-4个碳的烷氧基或它们一起形成C 2 -C 5 亚烷基二氧基或氧代基与烷基胺在还原剂或氢气存在下与氢化催化剂反应。 还描述了获得新的式（6）化合物的方法。

公开(公告)号：EP1286965A1

公开(公告)日：2003-03-05

申请号：EP00927979.5

申请日：2000-05-12

申请人： Synthon B.V.

发明人： PETERS, Theodorus, Hendricus, Antonius ,  LEMMENS, Jacobus, Maria ,  SLANINA, Pavel

IPC分类号： C07D211/22 ,  C07D405/12

CPC分类号： C07D211/22 ,  C07D405/12

摘要： Process for providing a compound of formula (6), a hydrate, solvate, and/or salt thereof, for example a pharmaceutically acceptable acid addition salt, comprising the step of reacting a compound of formula (1), with a tosyl moiety, providing compound.

公开(公告)号：EP1064275B1

公开(公告)日：2002-11-06

申请号：EP99909407.1

申请日：1999-03-05

申请人： Synthon B.V.

发明人： VAN DALEN, Frans ,  LEMMENS, Jacobus, Maria ,  VAN HELVOIRT, Gertruda, Antonetta, Philomina ,  PETERS, Theodorus, Hendricus, Antonius ,  PICHA, Frantisek

IPC分类号： C07D309/30 ,  C07D319/06 ,  C07D235/30

CPC分类号： C07D309/30 ,  C07C235/30 ,  C07C2602/28 ,  C07D319/06 ,  Y02P20/55

摘要： Process for the preparation of a compound of formula (VI), comprising the steps of: reacting a compound of general formula (I) with a ring-opening agent to provide a compound having general formula (II); protecting the hydroxy groups of the thus formed compound (II) with a pre-determined protective agent in order to substantially retard the reactivity thereof and provide a compound having general formula (III) or (VII), wherein the protective agent retards the reactivity of compound (II) by replacing the hydrogen atom of at least one of the hydroxy groups thereof with a carbon terminated group, whereby, in the case of compound (III) at least one of R?3 and R4¿ is not hydrogen; reacting compound (III) and/or (VII) with an alkylating agent of formula R7X to obtain a compound having formula (IV) or (VIII) respectively, wherein R7 preferably represents a methyl or ethyl group and X represents a halide, preferably chlorine, bromine or iodine; hydrolyzing the protective groups R?3, R4 and R5, R6¿ of compounds (IV) and (VIII) respectively to obtain a compound of formula (V); relactonizing compound (V) to yield compound (VI).

公开(公告)号：EP2170399A1

公开(公告)日：2010-04-07

申请号：EP08749503.2

申请日：2008-05-29

申请人： Synthon B.V.

发明人： VAN DER STERREN, Josephine, Elisabeth, Maria ,  VAN DER HEUVEL, Dennie, Johan, Marijn ,  LEMMENS, Jacobus, Maria

IPC分类号： A61K47/10 ,  A61K31/407 ,  A61K9/08

CPC分类号： A61K9/0043 ,  A61K31/407 ,  A61K47/10

摘要： Asenapine or a pharmaceutically acceptable salt thereof can be administered intranasally, typically via an intranasal dosage formulation having a water-containing liquid carrier.

公开(公告)号：EP1064275B2

公开(公告)日：2006-04-19

申请号：EP99909407.1

申请日：1999-03-05

申请人： Synthon B.V.

发明人： VAN DALEN, Frans ,  LEMMENS, Jacobus, Maria ,  VAN HELVOIRT, Gertruda, Antonetta, Philomina ,  PETERS, Theodorus, Hendricus, Antonius ,  PICHA, Frantisek

IPC分类号： C07D309/30 ,  C07D319/06 ,  C07D235/30

CPC分类号： C07D309/30 ,  C07C235/30 ,  C07C2602/28 ,  C07D319/06 ,  Y02P20/55

摘要： Process for the preparation of a compound of formula (VI), comprising the steps of: reacting a compound of general formula (I) with a ring-opening agent to provide a compound having general formula (II); protecting the hydroxy groups of the thus formed compound (II) with a pre-determined protective agent in order to substantially retard the reactivity thereof and provide a compound having general formula (III) or (VII), wherein the protective agent retards the reactivity of compound (II) by replacing the hydrogen atom of at least one of the hydroxy groups thereof with a carbon terminated group, whereby, in the case of compound (III) at least one of R?3 and R4¿ is not hydrogen; reacting compound (III) and/or (VII) with an alkylating agent of formula R7X to obtain a compound having formula (IV) or (VIII) respectively, wherein R7 preferably represents a methyl or ethyl group and X represents a halide, preferably chlorine, bromine or iodine; hydrolyzing the protective groups R?3, R4 and R5, R6¿ of compounds (IV) and (VIII) respectively to obtain a compound of formula (V); relactonizing compound (V) to yield compound (VI).

摘要翻译： 制备式（VI）化合物的方法，包括以下步骤：使通式（I）的化合物与开环剂反应，得到具有通式（II）的化合物; 用预定的保护剂保护由此形成的化合物（II）的羟基，以便基本上延迟其反应性并提供具有通式（III）或（VII）的化合物，其中保护剂延缓了 化合物（II）通过用至少一个羟基取代其末端基团的氢原子，因此在化合物（III）的情况下，R 3和R 4中的至少一个不是氢 ; 使化合物（III）和/或（VII）与式R 7 X的烷基化剂反应得到分别具有式（IV）或（VIII）的化合物，其中R 7优选表示甲基或乙基， X表示卤化物，优选氯，溴或碘; 分别水解化合物（Ⅳ）和（Ⅷ）的保护基R 3，R 4和R 5，R 6，得到式（Ⅴ）化合物; （V）化合物（VI）。

公开(公告)号：EP1163241B1

公开(公告)日：2005-06-15

申请号：EP00913159.0

申请日：2000-03-13

申请人： Synthon B.V.

发明人： ETTEMA, Gerrit, Jan, Bouke ,  LEMMENS, Jacobus, Maria ,  PETERS, Theodorus, Hendricus, Antonius ,  PICHA, Frantisek

IPC分类号： C07D471/04 ,  A61K31/437 ,  A61P25/20

CPC分类号： C07D471/04

摘要： The invention relates to a zolpidem salt, excluding the salt zolpidem tartrate exhibiting a melting endotherm corresponding to zolpidem free base upon heating from about 20 °C to about 250 °C at a rate of 5 °C/minute.

摘要翻译： 本发明涉及唑吡坦盐，不含盐唑吡坦酒石酸盐，以5℃/分钟的速度加热约20℃至约250℃，显示出与唑吡旦游离碱相当的熔融吸热。

公开(公告)号：EP1441713A1

公开(公告)日：2004-08-04

申请号：EP02780143.0

申请日：2002-11-06

申请人： Synthon B.V.

发明人： LEMMENS, Jacobus, Maria ,  PLATTEEUW, Johannes, Jan ,  VAN DALEN, Frans ,  ORTEGA, Arturo, Siles ,  ESCOI, Juan, Cucala

IPC分类号： A61K31/18 ,  A61K9/20 ,  A61K9/28 ,  A61K9/48 ,  A61P13/08

CPC分类号： A61K9/2009 ,  A61K9/2018 ,  A61K9/2027 ,  A61K9/2054 ,  A61K9/2095 ,  A61K9/2846 ,  A61K9/4808 ,  A61K31/18

摘要： The present invention is directed towards modified release tablets comprising a tablet matrix having dispersed therein tamsulosin or a pharmaceutically acceptable salt thereof and optionally having an enteric coating over said matrix with a dissolution profile such that in each of the media SIF, FaSSIF, and FeSSIF said tablet releases not more than 60% of said tamsulosin at 2 hours elapsed time in USP 2 apparatus using 500 ml of said media at 50-100 rpm paddle speed.

公开(公告)号：EP1368332A1

公开(公告)日：2003-12-10

申请号：EP02705606.8

申请日：2002-03-11

申请人： Synthon B.V.

发明人： PICHA, Frantisek ,  PETERS, Theodorus, Hendricus, Antonius ,  LEMMENS, Jacobus, Maria

IPC分类号： C07D309/30 ,  A61K31/366 ,  A61P3/06

CPC分类号： C07D309/30

摘要： A process for synthesizing a compound of formula (1) comprising the steps of intramolecular esterification, lactonization, of a compound of formula (2) with a lactonization agent in a suitable solvent thus yielding a reaction medium, wherein R is a hydrogen atom or a lower alkyl group, preferably a methyl group and X is a hydrogen atom or a cation, wherein the lactonization agent forms a hydrated complex with water, released on the lactonization of compound (2) into compound (1), which hydrated complex is substantially insoluble in the solvent.

摘要翻译： 一种合成式（1）化合物的方法，包括将式（2）化合物与内酯化试剂在合适溶剂中进行分子内酯化，内酯化的步骤，从而得到反应介质，其中R是氢原子或 低级烷基，优选甲基，X是氢原子或阳离子，其中内酯化试剂与水形成水合络合物，在化合物（2）内酯化成化合物（1）时释放，该水合络合物基本不溶解 在溶剂中。

公开(公告)号：EP1366042A1

公开(公告)日：2003-12-03

申请号：EP02712524.4

申请日：2002-02-18

申请人： Synthon B.V.

发明人： PICHA, Frantisek ,  PETERS, Theodorus, Hendricus, Antonius ,  LEMMENS, Jacobus, Maria

IPC分类号： C07D405/12 ,  A61K31/4525 ,  A61P25/00

CPC分类号： C07D405/12

摘要： The present invention relates to a method for preparing paroxetine of the formula (1) and pharmaceutically suitable salts thereof, comprising the hydrolysis, using a hydrolysing substance, of paroxetine phenyl carbamate of the formula (3) in a solvent composition comprising a sovent which is able to at least partially dissolve the hydrolysing substance.

摘要翻译： 本发明涉及制备式（1）帕罗西汀及其药学上适用的盐的方法，包括使用水解物质将式（3）的帕罗西汀苯基氨基甲酸酯在溶剂组合物中水解，所述溶剂组合物包含 能够至少部分地溶解水解物质。