公开(公告)号：US11724979B2

公开(公告)日：2023-08-15

申请号：US17377125

申请日：2021-07-15

申请人： CHINOIN GYÓGYSZER ÉS VEGYÉSZETI TERMÉKEK GYÁRA ZRT.

发明人： Imre Juhász ,  Irén Hortobágyi ,  Tamás Altsach ,  István Lászlófi ,  Ágnes Nagyné Borkó ,  Imre Rozsumberszki ,  Gábor Havasi ,  Zsuzsanna Kardos ,  Péter Buzder-Lantos

IPC分类号： C07C51/347 ,  C07C41/26 ,  C07C45/30 ,  C07C45/65 ,  C07C51/09 ,  C07C51/41 ,  C07C67/14 ,  C07C67/29 ,  C07C67/293 ,  C07C69/76 ,  C07C41/30 ,  C07C41/48 ,  C07C43/315 ,  C07C13/547 ,  C07C35/37 ,  C07C59/72

CPC分类号： C07C51/347 ,  C07C13/547 ,  C07C35/37 ,  C07C41/26 ,  C07C41/30 ,  C07C41/48 ,  C07C43/315 ,  C07C45/30 ,  C07C45/305 ,  C07C45/65 ,  C07C51/09 ,  C07C51/412 ,  C07C59/72 ,  C07C67/14 ,  C07C67/29 ,  C07C67/293 ,  C07C69/76 ,  C07C2603/14 ,  C07C45/305 ,  C07C49/84 ,  C07C45/30 ,  C07C49/84 ,  C07C45/65 ,  C07C49/755 ,  C07C51/09 ,  C07C59/70 ,  C07C41/48 ,  C07C43/315 ,  C07C67/14 ,  C07C69/76 ,  C07C67/29 ,  C07C69/76 ,  C07C67/293 ,  C07C69/76 ,  C07C51/412 ,  C07C59/70

摘要： Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anhydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates.

公开(公告)号：US10322990B2

公开(公告)日：2019-06-18

申请号：US15518096

申请日：2015-09-28

申请人： CHINOIN GYÓGYSZER ÉS VEGYÉSZETI TERMÉKEK GYÁRA ZRT.

发明人： Imre Juhász ,  Irén Hortobágyi ,  Tamás Altsach ,  István Lászlófi ,  Ágnes Nagyné Borkó ,  Imre Rozsumberszki ,  Gábor Havasi ,  Zsuzsanna Kardos ,  Péter Buzder-Lantos

IPC分类号： C07C51/347 ,  C07C41/26 ,  C07C45/30 ,  C07C45/65 ,  C07C51/09 ,  C07C51/41 ,  C07C67/14 ,  C07C67/29 ,  C07C67/293 ,  C07C69/76 ,  C07C41/30 ,  C07C41/48 ,  C07C43/315 ,  C07C13/547 ,  C07C35/37 ,  C07C59/72

摘要： Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates.

公开(公告)号：US11098001B2

公开(公告)日：2021-08-24

申请号：US16397139

申请日：2019-04-29

申请人： CHINOIN GYÓGYSZER ÉS VEGYÉSZETI TERMÉKEK GYÁRA ZRT.

发明人： Imre Juhász ,  Irén Hortobágyi ,  Tamás Altsach ,  István Lászlófi ,  Ágnes Nagyné Borkó ,  Imre Rozsumberszki ,  Gábor Havasi ,  Zsuzsanna Kardos ,  Péter Buzder-Lantos

IPC分类号： C07C51/347 ,  C07C41/26 ,  C07C45/30 ,  C07C45/65 ,  C07C51/09 ,  C07C51/41 ,  C07C67/14 ,  C07C67/29 ,  C07C67/293 ,  C07C69/76 ,  C07C41/30 ,  C07C41/48 ,  C07C43/315 ,  C07C13/547 ,  C07C35/37 ,  C07C59/72

摘要： Treprostinil is a synthetic prostacyclin derivative with thrombocyte aggregation inhibitory and vasodilatory activity. Treprostinil can be administered in subcutaneous, intravenous, inhalable, or oral forms. Disclosed is a method for the preparation of treprostinil of formula I and its amorphous form, anhydrate form, monohydrate form, and polyhydrate form salts with bases. In the disclosed method, the chiral center in the 3-hydroxyoctyl substituent is formed at the end of the synthesis, so that the method is robust and well scalable. Also disclosed are treprostinil intermediates and the preparation of the intermediates.

公开(公告)号：US10442762B2

公开(公告)日：2019-10-15

申请号：US15780896

申请日：2016-11-10

申请人： CHINOIN GYÓGYSZER ÉS VEGYÉSZETI TERMÉKEK GYÁRA ZRT.

发明人： Péter Buzder-Lantos ,  Zsuzsanna Kardos ,  Irén Hortobágyi ,  István Lászlófi ,  Imre Juhász ,  László Fónagy ,  Csaba Váradi ,  Ágnes Nagyné Borkó

IPC分类号： C07C405/00 ,  B01D15/26 ,  B01D15/42 ,  B01J20/10 ,  C07C7/12

摘要： The subject of the invention is a novel process for the preparation of Carboprost tromethamine salt where alkylation the enone of the general formula (II) is carried out in the presence of a chiral auxiliary in aprotic solvent with a Grignard reagent. The methyl ester epimers of formula (VII) are separated by gravity silica gel chromatography and the salt formation is carried out by using solid tromethamine base.