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公开(公告)号:US20240116874A1
公开(公告)日:2024-04-11
申请号:US18506737
申请日:2023-11-10
发明人: Britta OLENIK , Birgit KEIL , Bernd RÖSLER , Peter FEY , Heiko SCHIRMER , Guido BECKER , Julian EGGER , Clemens BOTHE , Helene FABER
IPC分类号: C07D215/48 , A61K9/00 , A61P9/12 , A61P11/08
CPC分类号: C07D215/48 , A61K9/0075 , A61P9/12 , A61P11/08
摘要: The present invention relates to a novel and improved process for preparing (5S)-{[2-(4-carboxyphenyl)ethyl][2-(2-{[3-chloro-4′-(trifluo-romethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]amino}-5,6,7,8-tetrahydroquinoline-2-carboxylic acid of the formula (I) and to novel crystalline forms of it, which is i.a. the pseudopolymorphic form monohydrate I (I-M-I) or the pseudopolymorphic form monohydrate II (I-M-II), furthermore the present invention relates to a novel and selective crystallization process for preparation of the pseudopolymorphic form monohydrate I (I-M-I) or the pseudopolymorphic form monohydrate II (I-M-II), preferably monohydrate I of formula (I-M-I) and to pharmaceutical compositions comprising monohydrate I of formula (I-M-I) and to its use for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of pulmonary and cardiopulmonary and cardiovascular diseases.
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公开(公告)号:US20240148715A1
公开(公告)日:2024-05-09
申请号:US18506944
申请日:2023-11-10
发明人: Eva Maria BECKER-PELSTER , Hanna TINEL , Michael HAHN , Dieter LANG , Gerrit WEIMANN , Johannes NAGELSCHMITZ , Lisa DIETZ , Soundos SALEH , David JUNG , Ildiko TEREBESI , Tobias MUNDRY , Annett RICHTER , Britta OLENIK , Birgit KEIL , Bernd RÖSLER , Peter FEY , Heiko SCHIRMER , Guido BECKER , Clemens BOTHE , Helene FABER , Julian EGGER , Mark PARRY , David WARD , Cecile VITRE
CPC分类号: A61K31/47 , A61K9/0075 , A61P9/12
摘要: The present invention relates to the use of (5S)-{[2-(4-carboxyphenyl)ethyl][2-(2-{[3-chloro-4′-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxylic acid of formula (I), prefer-ably in form of one of its salts or solvates or hydrates, preferably (5S)-{[2-(4-carboxyphenyl)ethyl][2-(2-{[3-chloro-4′-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxylic acid in form of monohydrate (I) of formula (I-M-I) or (5S)-{[2-(4-carboxyphenyl)ethyl][2-(2-{[3-chloro-4′-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)-ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxylic acid inform of mono hydrate (II) of formula (I-M-II), in the inhalative treatment of cardiopulmonary and pulmonary disorders, such as pulmonary arterial hypertension (P AH), chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary hypertension (PH) associated with chronic lung disease (PH group 3) such as pulmonary hypertension in chronic obstructive pulmonary disease (PH-COPD) and pulmonary hypertension with idiopathic interstitial pneumonia (PH-IIP), characterized in that an inhalative dosage form comprising 240 to 4000 μg, preferably 480 to 2000 μg of (5S)-{[2-(4-carboxyphenyl)ethyl][2-(2-{[3-chloro-4′-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxy lie acid of formula (I), preferably in form of one of its salts or solvates or hydrates, preferably in form of monohydrate I of formula (I-M-I) or (5S)-{[2-(4-carboxyphenyl)ethyl][2-(2-{[3-chloro-4′-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]-amino}-5,6,7,8-tetrahydroquinoline-2-carboxy lie acid in form of mono hydrate (II) of formula (I-M-II), is administered to a patient in need thereof once or twice daily for a period of at least two consecutive days, preferably at least 2 to 7 consecutive days, preferably for a period of at least 14 consecutive days, in particular from after onset of treatment for the whole course of the disease, wherein the inhalative dosage form preferably comprises the combination of the active ingredient and a pharmaceutically suitable excipient or carrier, while preferably the active ingredient and a pharmaceutically suitable excipient are filled in a hard capsule.
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公开(公告)号:US20180155336A1
公开(公告)日:2018-06-07
申请号:US15568575
申请日:2016-05-02
发明人: Franz-Josef MAIS , Werner HEILMAN , Britta OLENIK , Birgit KEIL , Guido BECKER , Daniel MEIBOM , Thomas KUHLMANN
IPC分类号: C07D417/12
CPC分类号: C07D417/12 , A61K47/64 , C07K5/06026
摘要: The present application relates to a novel and improved process for preparing the compound 2-{4-[2-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulphanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl]phenoxy}ethyl-L-alanyl L-alaninate monohydrochloride of the formula (I) to novel precursors for its preparation, and to the preparation and use of crystal modification I of 2-{4-[2-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulphanyl)-3,5-dicyano-6-(pyrrolidin-1-yl)pyridin-4-yl]phenoxy}-ethyl-L-alanyl L-alaninate monohydrochloride of the formula (I).
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