公开(公告)号：US20110009654A1

公开(公告)日：2011-01-13

申请号：US12739195

申请日：2008-10-18

申请人： Orlin Petrov ,  Matthias Schneider ,  Rolf Bohlmann ,  Stephan Vettel

发明人： Orlin Petrov ,  Matthias Schneider ,  Rolf Bohlmann ,  Stephan Vettel

IPC分类号： C07J75/00 ,  C07J1/00

CPC分类号： C07J1/0059

摘要： The present invention relates to 11β-fluoro-3-acetoxyestra-3,5-dien-17-one as a suitable intermediate in the preparation of 11-fluoro-substituted steroids and to the process for preparation thereof. For this purpose, 11α-hydroxyestra-4-ene-3,17-dione is reacted with 1 to 3 equivalents of n-nonafluorobutanesulfonyl fluoride and 3 to 5 equivalents of diazabicycloundecene (DBU) at −40 to −20° C. in an organic aprotic solvent and, after an aqueous workup, reacted with 5 to 10 equivalents of acetic anhydride and 0.01 to 1 equivalent of a strong acid. The desired product precipitates spontaneously out of the reaction solution and is obtained in a very high purity by filtration. The process is notable for the very high yield, avoidance of a chromatographic purification of the product, a reduced proportion of wastes and significantly increased process throughput. The process according to the invention is therefore especially suitable for preparing 11β-fluoro-3-acetoxyestra-3,5-dien-17-one on a large industrial scale.

摘要翻译： 本发明涉及11-氟-3-乙酰氧基雌-3,5-二烯-17-酮作为制备11-氟取代的类固醇的合适中间体及其制备方法。 为此，将11α-羟基雌-4-烯-3,17-二酮与1至3当量的正 - 九氟丁磺​​酰氟和3至5当量的二氮杂双环十一碳烯（DBU）在-40至-20℃下反应， 有机非质子溶剂，在水处理后，与5至10当量的乙酸酐和0.01至1当量的强酸反应。 所需产物自发地从反应溶液中沉淀出来，通过过滤得到非常高的纯度。 该方法是非常高的产量，避免产品的色谱纯化，减少的废物比例和显着增加的工艺生产量。 因此，根据本发明的方法特别适用于大型工业规模的制备11-全氟-3-乙酰氧基雌-3,5-二烯-17-酮。

公开(公告)号：US07538100B2

公开(公告)日：2009-05-26

申请号：US11188992

申请日：2005-07-26

申请人： Rolf Bohlmann ,  Nikolaus Heinrich ,  Rolf Jautelat ,  Jorg Kroll ,  Orlin Petrov ,  Andreas Reichel ,  Jens Hoffmann ,  Rosemarie Lichtner

发明人： Rolf Bohlmann ,  Nikolaus Heinrich ,  Rolf Jautelat ,  Jorg Kroll ,  Orlin Petrov ,  Andreas Reichel ,  Jens Hoffmann ,  Rosemarie Lichtner

IPC分类号： A61K31/56 ,  C07J1/00

CPC分类号： C07J43/003 ,  C07J41/0072

摘要： The invention relates to 17α-alkyl-17β-oxy-estra-1,3,5(10)-trienes that have an antiestrogenic action with general formula I. In addition, the invention also relates to 17-oxo-estra-1,3,5(10)-trienes as well as 17β-hydroxy-estra-1,3,5(10)-trienes as intermediate products in the production of the estratrienes according to the invention. The invention also relates to the use of 17α-alkyl-17β-oxy-estratrienes for the production of pharmaceutical agents as well as pharmaceutical preparations that contain at least one 17α-alkyl-17β-oxy-estratriene as well as at least one pharmaceutically compatible vehicle.

摘要翻译： 本发明涉及具有通式I的抗雌激素作用的17α-烷基-17β-氧 - 雌-1,3,5（10） - 三烯。此外，本发明还涉及17-氧代 - 雌-1 3,5（10） - 三烯以及17β-羟基 - 雌-1,3,5（10） - 三烯作为生产根据本发明的雌三醇的中间产物。 本发明还涉及17α-烷基-17β-氧 - 雌三烯在制备药剂中的用途以及含有至少一种17α-烷基-17β-氧 - 雌三醇的药物制剂以及至少一种药物相容性 车辆。

公开(公告)号：US20060009436A1

公开(公告)日：2006-01-12

申请号：US11188992

申请日：2005-07-26

申请人： Rolf Bohlmann ,  Nikolaus Heinrich ,  Rolf Jautelat ,  Jorg Kroll ,  Orlin Petrov ,  Andreas Reichel ,  Jens Hoffmann ,  Rosemarie Lichtner

发明人： Rolf Bohlmann ,  Nikolaus Heinrich ,  Rolf Jautelat ,  Jorg Kroll ,  Orlin Petrov ,  Andreas Reichel ,  Jens Hoffmann ,  Rosemarie Lichtner

IPC分类号： A61K31/57

CPC分类号： C07J43/003 ,  C07J41/0072

摘要： The invention relates to 17α-alkyl-17β-oxy-estra-1,3,5(10)-trienes that have an antiestrogenic action with general formula I. In addition, the invention also relates to 17-oxo-estra-1,3,5(10)-trienes as well as 17β-hydroxy-estra-1,3,5(10)-trienes as intermediate products in the production of the estratrienes according to the invention. The invention also relates to the use of 17α-alkyl-17β-oxy-estratrienes for the production of pharmaceutical agents as well as pharmaceutical preparations that contain at least one 17α-alkyl-17β-oxy-estratriene as well as at least one pharmaceutically compatible vehicle.

公开(公告)号：US07018994B2

公开(公告)日：2006-03-28

申请号：US10305418

申请日：2002-11-27

申请人： Rolf Bohlmann ,  Nikolaus Heinrich ,  Rolf Jautelat ,  Jorg Kroll ,  Orlin Petrov ,  Andreas Reichel ,  Jens Hoffmann ,  Rosemarie Lichtner

发明人： Rolf Bohlmann ,  Nikolaus Heinrich ,  Rolf Jautelat ,  Jorg Kroll ,  Orlin Petrov ,  Andreas Reichel ,  Jens Hoffmann ,  Rosemarie Lichtner

IPC分类号： A61K31/56 ,  C07J1/00

CPC分类号： C07J43/003 ,  C07J41/0072

摘要： The invention relates to 17α-alkyl-17β-oxy-estra-1,3,5(10)-trienes that have an antiestrogenic action with general formula I. In addition, the invention also relates to 17-oxo-estra-1,3,5(10)-trienes as well as 17β-hydroxy-estra-1,3,5(10)-trienes as intermediate products in the production of the estratrienes according to the invention. The invention also relates to the use of 17α-alkyl-17β-oxy-estratrienes for the production of pharmaceutical agents as well as pharmaceutical preparations that contain at least one 17α-alkyl-17β-oxy-estratriene as well as at least one pharmaceutically compatible vehicle.

摘要翻译： 本发明涉及具有通式I的抗雌激素作用的17α-烷基-17β-氧 - 雌-1,3,5（10） - 三烯。此外，本发明还涉及17-氧代 - 雌-1 3,5（10） - 三烯以及17β-羟基 - 雌-1,3,5（10） - 三烯作为生产根据本发明的雌三醇的中间产物。 本发明还涉及17α-烷基-17β-氧 - 雌三烯在制备药剂中的用途以及含有至少一种17α-烷基-17β-氧 - 雌三醇的药物制剂以及至少一种药物相容性 车辆。

公开(公告)号：US09669034B2

公开(公告)日：2017-06-06

申请号：US14122063

申请日：2012-05-21

申请人： Ulrich Lücking ,  Rolf Bohlmann ,  Arne Scholz ,  Gerhard Siemeister ,  Mark Jean Gnoth ,  Ulf Bömer ,  Dirk Kosemund ,  Philip Lienau ,  Gerd Rühter ,  Carsten Schultz-Fademrecht

发明人： Ulrich Lücking ,  Rolf Bohlmann ,  Arne Scholz ,  Gerhard Siemeister ,  Mark Jean Gnoth ,  Ulf Bömer ,  Dirk Kosemund ,  Philip Lienau ,  Gerd Rühter ,  Carsten Schultz-Fademrecht

IPC分类号： C07D251/42 ,  C07D251/44 ,  C07D405/04 ,  A61K31/53 ,  A61P35/00 ,  C07D251/16 ,  C07D251/22 ,  C07D401/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07C381/10

CPC分类号： A61K31/53 ,  C07B59/002 ,  C07B2200/05 ,  C07C381/10 ,  C07D251/16 ,  C07D251/22 ,  C07D251/42 ,  C07D251/44 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12

摘要： The present invention relates to 4-aryl-N-phenyl-1,3,5-triazin-2-amines containing a sulfoximine group of general formula (I) or (Ia) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I) or (Ia).

公开(公告)号：US09284317B2

公开(公告)日：2016-03-15

申请号：US13994335

申请日：2011-12-13

申请人： Marcus Koppitz ,  Ulrich Klar ,  Rolf Jautelat ,  Dirk Kosemund ,  Rolf Bohlmann ,  Benjamin Bader ,  Philip Lienau ,  Gerhard Siemeister

发明人： Marcus Koppitz ,  Ulrich Klar ,  Rolf Jautelat ,  Dirk Kosemund ,  Rolf Bohlmann ,  Benjamin Bader ,  Philip Lienau ,  Gerhard Siemeister

IPC分类号： A61K31/4985 ,  C07D241/36 ,  C07D487/04 ,  C07D403/02

CPC分类号： C07D487/04 ,  C07D403/02

摘要： The present invention relates to substituted imidazopyrazine compounds of general formula (I): in which R1, R2, R3, R4 and R5 are as defined in the claims, to methods of and intermediates for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

摘要翻译： 本发明涉及通式（I）的取代的咪唑并嗪化合物：其中R 1，R 2，R 3，R 4和R 5如权利要求中所定义，涉及制备所述化合物的方法和中间体，药物组合物和组合，其包含所述 化合物和所述化合物用于制备用于治疗或预防疾病，特别是高增殖和/或血管生成障碍的药物组合物作为唯一试剂或与其它活性成分组合的用途。

公开(公告)号：US08916557B2

公开(公告)日：2014-12-23

申请号：US14112484

申请日：2012-04-18

申请人： Ulrich Lücking ,  Rolf Bohlmann ,  Arne Scholz ,  Gerhard Siemeister ,  Mark Jean Gnoth ,  Ulf Bömer ,  Gerd Rühter ,  Carsten Schultz-Fademrecht ,  Dirk Kosemund ,  Philip Lienau

发明人： Ulrich Lücking ,  Rolf Bohlmann ,  Arne Scholz ,  Gerhard Siemeister ,  Mark Jean Gnoth ,  Ulf Bömer ,  Gerd Rühter ,  Carsten Schultz-Fademrecht ,  Dirk Kosemund ,  Philip Lienau

IPC分类号： C07D251/42 ,  C07D401/04 ,  C07D405/04 ,  C07D401/12 ,  C07D405/12

CPC分类号： C07D251/42 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04 ,  C07D405/12

摘要： The present invention relates to substituted 4-Aryl-N-phenyl-1,3,5-triazin-2-amines of general formula (I) as described and defined herein, and methods for their preparation, their use for the treatment and/or prophylaxis of disorders, in particular of hyper-proliferative disorders and/or virally induced infectious diseases and/or of cardiovascular diseases. The invention further relates to intermediate compounds useful in the preparation of said compounds of general formula (I).

摘要翻译： 本发明涉及如本文所述和定义的通式（I）的取代的4-芳基-N-苯基-1,3,5-三嗪-2-胺及其制备方法及其用于治疗和/ 或预防疾病，特别是高增殖性疾病和/或病毒诱导的传染病和/或心血管疾病。 本发明还涉及可用于制备所述通式（I）化合物的中间体化合物。

公开(公告)号：US20130281460A1

公开(公告)日：2013-10-24

申请号：US13995055

申请日：2011-12-13

申请人： Marcus Koppitz ,  Ulrich Klar ,  Rolf Jautelat ,  Dirk Kosemund ,  Rolf Bohlmann ,  Benjamin Bader ,  Philip Lienau ,  Gerhard Siemeister

发明人： Marcus Koppitz ,  Ulrich Klar ,  Rolf Jautelat ,  Dirk Kosemund ,  Rolf Bohlmann ,  Benjamin Bader ,  Philip Lienau ,  Gerhard Siemeister

IPC分类号： C07D487/04

CPC分类号： C07D487/04

摘要： The present invention relates to substituted imidazopyrazine compounds of general formula (I): (I) in which R1, R2, R3, R4 and R5 are as defined in the claims, to methods of and intermediates for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of a hyper-proliferative and/or angiogenesis disorder, as a sole agent or in combination with other active ingredients.

摘要翻译： 本发明涉及通式（I）的取代的咪唑并吡嗪化合物：其中R 1，R 2，R 3，R 4和R 5如权利要求中所定义，其中R 1，R 2，R 3，R 4和R 5如上述定义的方法和制备所述化合物的中间体， 包含所述化合物的组合以及所述化合物用于制备用于治疗或预防疾病，特别是高增殖性和/或血管生成障碍的药物组合物作为唯一试剂或与其它活性成分组合的用途。

公开(公告)号：US20110015162A1

公开(公告)日：2011-01-20

申请号：US12811002

申请日：2008-12-23

申请人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Huebner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

发明人： Ulrich Klar ,  Joachim Kuhnke ,  Rolf Bohlmann ,  Jan Huebner ,  Sven Ring ,  Thomas Frenzel ,  Frederik Menges ,  Steffen Borden ,  Hans Peter Muhn ,  Katja Prelle

IPC分类号： A61K31/58 ,  C07J53/00 ,  A61K31/56

CPC分类号： C07J53/008

摘要： The invention relates to 15,16-methylene-17-hydroxy-19-nor-21-carboxylic acid-steroid γ-lactone derivatives with the general chemical formula I, and R4, R6a, R6b, R7 and Z have the meanings stated in claim 1, and their solvates, hydrates, stereoisomers and salts. The invention further relates to the use of these derivatives for the production of a medicinal product for oral contraception and for the treatment of pre-, peri- and postmenopausal complaints and medicinal products that contain said derivatives. The derivatives according to the invention have a progestational and in preferred cases additionally an antimineralocorticoid and neutral to slightly androgenic action.

摘要翻译： 本发明涉及具有一般化学式I的15,16-亚甲基-17-羟基-19-去甲-21-羧酸 - 类固醇γ-内酯衍生物，且R4，R6a，R6b，R7和Z具有以下含义： 权利要求1及其溶剂合物，水合物，立体异构体和盐。 本发明还涉及这些衍生物用于生产口服避孕用药物和用于治疗前，绝经前和绝经后的投诉和含有所述衍生物的药用产品的用途。 根据本发明的衍生物具有促孕作用，在优选情况下另外具有抗皮质激素和中性至轻度雄激素作用。

公开(公告)号：US07361645B2

公开(公告)日：2008-04-22

申请号：US10467352

申请日：2002-01-24

申请人： Rolf Bohlmann ,  Hermann Kuenzer ,  Reinhard Nubbemeyer ,  Dieter Zopf

发明人： Rolf Bohlmann ,  Hermann Kuenzer ,  Reinhard Nubbemeyer ,  Dieter Zopf

IPC分类号： A61K31/56 ,  C07J1/00

CPC分类号： C07J1/0074 ,  C07J1/0022 ,  C07J1/0025 ,  C07J1/007

摘要： The invention relates to 11β-halogen steroids with general formula (I), whereby R11 is halogen, X—Y-Z represents a group with one of the two structures CH═C—C or CH2—C═C and the other radicals have the meaning that is indicated in the claims, also the production and use of these compounds for the production of pharmaceutical agents as well as pharmaceutical preparations that contain 11β-halogen steroids.

摘要翻译： 本发明涉及具有通式（I）的11b-卤素类固醇，其中R 11是卤素，XYZ代表具有两个结构之一的CH-CC或CH 2 2的基团 > -CC，其它基团具有权利要求书中所示的含义，以及这些化合物用于生产药物的生产和使用以及含有11b-卤素类固醇的药物制剂。