Bayer Aktiengesellschaft

Adverio Pharma Gmbh

Bayer Pharma Aktiengesellschaft

Bayer Intellectual Property Gmbh

Bayer Healthcare Aktiengesellschaft

Bayer Animal Health Gmbh

Bayeraktiengesellschaft

Adverio Pharm Gmbh

Ardea Biosciences, Inc

Elanco Animal Health Gmbh

Peter Fey

Walter Hubsch

Hilmar Bischoff

Johannes-Peter Stasch

Andreas Knorr

Delf Schmidt

Martin Beuck

Rolf Angerbauer

Stefan Wohlfeil

Rudolf H Hanko

Stanislav Kazda

Thomas Kramer

Ulrich E Muller

Matthias Muller-Gliemann

Jurgen Dressel

Dieter Petzinna

Thomas Philipps

Siegfried Zaiss

Gunter Thomas

Dirk Denzer

Claudia Hirth-Dietrich

Joachim Mittendorf

Hans-Peter Krause

Rudolf Schohe-Loop

Bodo Junge

Heinrich Meier

Alfons Grunenberg

Britta Olenik

Johannes Kaulen

Donald Bierer

Erwin Bischoff

Paul Naab

Heiko Schirmer

Birgit Keil

Siegfried Goldmann

Sergii Pazenok

Dieter Lang

Christian Funke

Felix Spindler

Michael Hahn

Hanna Tinel

Hans-Christian Militzer

Michael Matzke

Ulrich Niewohner

Klaus-Helmut Mohrs

Lisa Dietz

Ralf Wischnat

Werner Hoheisel

Ozkan Yalkinoglu

Kai Van Laak

Matthias M uller-Gliemann

Ulrich E M Uller

J Urgen Dressel

Jan-Bernd Lenfers

Thomas Kr Amer

Walter H Ubsch

Guido Becker

Klaus Frobel

Hans-Georg Dellweg

Joachim Bender

Markus Longerich

Clemens Bothe

Julian Egger

Jorg Petersen Von Gehr

Helene Faber

Bernd Rösler

Eva Maria Becker-Pelster

Hermann Arold

Mathias Berwe

Kai Lovis

Hartwig Muller

Philipp Rubenbauer

Martin Radtke

Walter H&uuml;bsch

Ildiko Terebesi

Anja Ehrig

Yuriy Grigorievich Shermolovich

Wolfgang Kanhai

Julia Küsel

Michal Sowa

Wolfgang Karl

Heike Neumann

Annett Richter

Gu/ Nter Thomas

Michael Ostendorf

Thomas Gunter

Agathe Christine Mayer

Peter Petzinna

Walter Husch

Jorg Peterson-von Gehr

Stanisiav Kazda

Walter Hu/ Bsch

Thomas Philipps, Deceased

Natalya Pavlovna Kolesnik

Olexandr Ivanovich Guzyr

Johannes Nagelschmitz

Elisabeth Kersten

Joerg Brockob

Joerg Wirths

Antje Dietzel

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.

Process for preparing (5S)-{[2-(4-carboxyphenyl)ethyl] |2-(2-{|3-chloro-4'-(trifluoromethyl)biphenyl-4-yl]methoxy}phenyl)ethyl]aminol-5,6,7,8-tetrahydroquinoline-2-carboxylic acid and its crystalline forms for use as pharmaceutically active compound

The present invention relates to methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate in the form of a novel active compound product having improved properties, for example in respect of the isolability of the active compound product, the dischargeability of the active compound product after isolation and drying and also conveyability, sieveability and micronizability of the active compound product, and to processes for the production and formulation thereof.

Methyl {4,6-diamino-2-[5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}carbamate active compound product having improved properties, production and formulation thereof

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 tromboembolic 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.

Treatment of cardiopulmonary disorders

The present application relates to a novel, cost-saving and efficient process for preparing 4-(2,2,3,3-tetrafluoropropyl)morpholine which serves as an intermediate for production of medicaments and for production of medicaments for treatment and/or prophylaxis of cardiovascular disorders.

Process for manufacturing 4-(2,2,3,3-tetrafluoropropyl)morpholine

The present invention relates to a novel and improved process for preparing (3S)-3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropylpropanoic acid of the formula (I), to the compound of the formula (I) in crystalline form and to their use for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular, cardiopulmonary and cardiorenal disorders.

Method for producing (3S)-3-(4-chloro-3-{[(2S,3R)-2-(4- chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclo-propylpropanoic acid and the crystalline form thereof for use as a pharmaceutical  ingredient

Quinolonecarboxylic esters of the general formula (II) are hydrolyzed to quinolonecarboxylic acids of the general formula (I):  The method comprises the step A): A) reacting compounds of the formula (II) with a mixture comprising acetic acid, sulfuric acid and water In step A), &#x2265;30 to &#x2264;40 mol of acetic acid, &#x2265;0.3 to &#x2264;1 mol of sulfuric acid and &#x2265;0.9 to &#x2264;2.5 mol of water are used per mole of compounds of the formula (II). The method is particularly suitable for the synthesis of the intermediate (I) in the synthesis of pradofloxacin.

Method for the hydrolysis of quinolonecarboxylic esters

The present application relates to a novel and efficient process for preparing novel substituted 5-fluoro-1H-pyrazolopyridines of the formula (VI) which are suitable as an intermediate for production of medicaments and for production of medicaments for treatment and/or prophylaxis of cardiovascular disorders. More particularly, the 5-fluoro-1H-pyrazolopyridines of the formula (VI) are suitable for preparation of the compound of the formula (I) which serves for production of medicaments, for production of medicaments for treatment and/or prophylaxis of cardiovascular disorders.

Hydrates of substituted 5-fluoro-1H-pyrazolopyridines

Intermediates and process for preparing intermediates in the production of substituted pyrazolopyridines

Crystalline substituted 5-fluoro-1H-pyrazolopyridines and process for preparing

Process for preparing substituted 5-fluoro-1H-pyrazolopyridines

The present invention relates to a novel enantioselective method of preparing (S)- and (R)-enantiomers of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-5 methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamide, to novel intermediate compounds, and to the use of said novel intermediate compounds for the preparation of said (S)- and (R)-enantiomers of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamide. 

Chiral synthesis of N-{3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-6-methoxyphenyl}-1-[2,3-dihydroxy-propyl]cyclopropanesulfonamides

The enantiomers of methyl 4-(2-chloro-4-fluorophenyl)-2-(3,5-difluoro-2-pyridinyl)-6-methyl)-1,4-dihydro-5-pyrimidinecarboxylate can be separated with the aid of (&#x2212;)-camphanic acid.

Method for separating methyl 4-(2-chloro-4-fluorophenyl)-2-(3,5-difluoro-2-pyridinyl)-6-methyl-1,4-dihydro-5-pyrimidine-carboxylate-recemate

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Wuppertal, Germany

Peter Fey