SINGLE-PIECE FEEDER BODY FOR USE IN METAL CASTING

The invention relates to a single-piece feeder body for use as a component of a two-part or multi-part telescopic feeder insert in metal casting, 114040. A single-piece feeder body () for use as a component of a two-part or multi-part telescopic feeder insert ( , ′) in metal casting ,{'b': 2', '42', '42', '2, 'claim-text': [{'b': 12', '42', '42, 'a passage opening () for the liquid metal into the feeder cavity (, ′), and'}, {'b': 6', '10', '8', '14', '20', '20', '1, 'an outer surface () on which there are arranged at least one outwardly projecting holding element () and at least one guide part () with a sliding section () for a feeder element (, ′) which corresponds with the feeder body (),'}], 'having a feeder wall () which at least partially delimits a feeder cavity (, ′) for receiving liquid metal, wherein the feeder wall () has'}{'b': 8', '16', '6', '14', '8', '20', '20', '12, 'wherein the guide part () has a supporting section () which protrudes outwardly on the outer surface () and which, adjoining the sliding section () of the guide part () for guiding the feeder element (, ′), extends in the direction of the passage opening ().'}21. The feeder body () as claimed in claim 1 ,{'b': 14', '34', '16', '36', '34', '1', '26', '36', '2', '26', '12', '1', '2, 'wherein the sliding section () has a sliding surface () and the supporting section () has a terminating surface (), wherein the sliding surface () runs so as to be inclined at an angle (α) with respect to the central axis (), and the terminating surface () runs so as to be inclined at an angle (α) with respect to the central axis () of the passage opening (), wherein the angles (α, α) open in opposite directions.'}31. The feeder body () as claimed in claim 1 ,{'b': 8', '12', '26', '12, 'wherein multiple guide parts () are arranged at angular intervals with respect to one another about the central axis of the passage opening (), preferably at uniform angular intervals about the central axis () of the passage ...

SHIFTING DEVICE

A shifting device for a transmission of a motor vehicle has an actuation lever () which can be selectively transferred into (a) a first selector gate, more particularly an automatic selector gate, in which the lever is mechanically coupled to a transmitting component () for actuating a gearshift cable or a gearshift linkage, or (b) a second selector gate, more particularly a sequential selector gate, in which the lever is decoupled from the transmitting component, the transmitting component being movably mounted, more particularly pivotably mounted. A locking means () can immobilize the transmitting component such that no force is exerted on the gearshift cable or the gearshift linkage as long as the actuation lever has been transferred into the second selector gate. The transmitting component may be released by a transfer of the actuation lever into the first selector gate. 1. A shifting device for the transmission of a motor vehicle , comprising:{'b': 1', '2', '2', '2, 'an actuation lever () selectively movable into either (a) a first automatic shift gate in which said lever is mechanically coupled to a transmitting component () for actuating a gearshift cable or a gearshift linkage, or (b) a second sequential shift gate in which the lever is uncoupled from the transmitting component (), wherein the transmitting component () is movably mounted; and'}{'b': 11', '2', '1', '2', '1, 'a locking means () adapted to secure the transmitting component () without exerting any force onto the gearshift cable or onto the gearshift linkage as long as the actuation lever () has been moved into the second shift gate, and adapted to release the transmitting component () when the actuation lever () is moved into the first shift gate.'}2. The shifting device according to claim 1 , characterized in that the actuation lever operates the locking means.3. The shifting device according to claim 1 , wherein{'b': 2', '2, 'a. the locking means is movable with the actuation lever out of a ...

AMIDE-SUBSTITUTED PYRIDINYLTRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel 5-(carboxamide)-1-pyridinyl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 3. The compound as defined in for use in a method for treatment of at least one selected from the group consisting of acute and chronic kidney diseases claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome claim 1 , and dysmenorrhea.4. Compound as defined in for use in a method for treatment of diabetic nephropathy.5. Pharmaceutical composition comprising a compound as defined in claim 1 , and one or more pharmaceutically acceptable excipients.6. Pharmaceutical composition of comprising one or more first active ingredients claim 4 , which are compounds of general formula (I) claim 4 , and one or more further active ingredients claim 4 , which are one or more additional therapeutic agents selected from the group consisting of diuretics claim 4 , angiotensin AII antagonists claim 4 , ACE inhibitors claim 4 , beta-receptor blockers claim 4 , mineralocorticoid receptor antagonists claim 4 , antidiabetics claim 4 , organic nitrates and NO donors claim 4 , activators and stimulators of the soluble guanylate cyclase (sGC) claim 4 , antiinflammatory agents claim 4 , immunosuppressive agents claim 4 , phosphate binders claim 4 , and/or compounds that modulate vitamin D metabolism.7. The pharmaceutical composition as defined in for treatment of at least one selected from the group consisting of acute kidney disease claim 4 , chronic kidney disease claim 4 , acute heart failure claim 4 , chronic heart failure claim 4 , preeclampsia claim 4 , peripheral arterial ...

ORALLY ADMINISTRABLE MODIFIED-RELEASE PHARMACEUTICAL DOSAGE FORM

The present invention relates to orally administrable modified-release pharmaceutical dosage forms comprising sodium (3S)-3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropylpropanoate and to processes for preparing the dosage forms and to their use for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiac, renal and pulmonary disorders, disorders of the central nervous system, fibrotic and inflammatory disorders and metabolic disorders. 2. The compound of the formula (II) according to claim 1 , in crystalline form of modification 1 claim 1 , characterized in that the X-ray diffractogram of the compound has peak maxima of the 2 theta angle at 8.1 claim 1 , 17.2 claim 1 , 18.8 claim 1 , 22.3 and 22.6°.3. The compound of the formula (II) according to claim 1 , in crystalline form of modification 1 claim 1 , characterized in that the IR spectrum of the compound has band maxima at 3381 claim 1 , 1691 claim 1 , 1565 claim 1 , 1524 and 1419 cm−1.5. The method of claim 4 , wherein the polar aprotic solvent used is acetonitrile and the base used is sodium hydroxide in solid form.6. The method of claim 4 , wherein the solvent used is acetonitrile and the base used is sodium tert-butoxide or sodium 2-methylbut-2-oxide.7. The method of claim 4 , wherein the base is added in an amount of 0.7 to 1.0 molar equivalents claim 4 , based on the compound of the formula (I).8. (canceled)9. (canceled)10. A medicament comprising the compound as of in combination with one or more other active ingredients selected from the group consisting of organic nitrates claim 1 , NO donors claim 1 , cGMP-PDE inhibitors claim 1 , stimulators of guanylate cyclase claim 1 , antithrombotics claim 1 , antihypertensive agents claim 1 , MR antagonists claim 1 , IP receptor agonists claim 1 , compounds having anti-inflammatory action claim 1 , antidementives claim 1 , antidiabetics claim 1 , active ...

ACTUATOR, DEVICE FOR ENGAGING A PARKING LOCK OF A MOTOR-VEHICLE AUTOMATIC TRANSMISSION HAVING SUCH AN ACTUATOR AND MOTOR VEHICLE EQUIPPED THEREWITH

The invention relates to an actuator, comprising a drive () that drives a drive shaft (), a first actuating element () operatively connected to the drive shaft () for actuating a switching apparatus, a spring element (), which can be supported at one end on a housing component () of the actuator and is supported on the other end on a second actuating element () designed to load the spring element (). The actuator according to the invention is characterized in that a rotatably mounted rotational element () that can be driven by means of the drive shaft () is provided, which rotational element has, on one side, a first control gate (), which is operatively connected to the first actuating element () for actuation of the switching apparatus, and on the other side, a second control gate () for loading the spring element (). 1. An actuator , comprising:{'b': 2', '1, 'a drive () configured for driving a drive shaft (),'}{'b': 3', '1, 'a first actuating element () operatively connected to the drive shaft () configured for actuating a shifting device,'}{'b': 5', '16', '17', '5, 'a spring element () supported at one end on a housing component () of the actuator and at its opposite end on a second actuating element () configured to load the spring element (),'}{'b': 4', '1, 'a rotary element () defining an axis of rotation and adapted to be rotatably driven using the drive shaft (),'}{'b': 7', '3, 'a first control cam () rotatable about the axis of rotation and operatively connected to the first actuating element () and configured to actuate the shifting device, and'}{'b': 8', '5, 'a second control cam () rotatable about the axis of rotation and configured to load the spring element ().'}2203721178. The actuator according to claim 1 , further comprising a first engagement element () of the first actuating element () configured to strike or engage in the first control cam () claim 1 , and a second engagement element () of the second actuating element () configured to strike or ...

ARRANGEMENT FOR USE IN THE PRODUCTION OF A SEPARABLE CASTING MOULD

An arrangement for use in the production of a separable casting mould, preferably of a vertically separable casting mould is disclosed. The arrangement can include (i) a mould plate and/or a mould pattern, (ii) a feeder system having a feeder element and having a feeder insert, wherein feeder element and feeder insert delimit a feeder cavity for receiving liquid metal. The arrangement also includes one or more tipping prevention elements which are designed to counteract tipping of the feeder system out of the opening axis about the first end of the feeder element when, in the event of the feeder system being acted on with a force acting parallel to the opening axis and in the direction of the first end, the side wall deforms and the spacing between the first and second ends is reduced, wherein the one or more tipping prevention element(s) are/is spaced apart from the opening axis. 1. Arrangement for use in the production of a separable casting mould , comprising:{'b': 4', '4', '6, '(i) a mould plate (, ′) and/or a mould pattern (),'}{'b': 8', '8', '8', '8', '8', '8', '10', '10', '10', '10', '10', '10', '12', '12', '12', '12', '12', '10', '10', '10', '10', '10', '10', '14, 'sup': IV', 'V', 'IV', 'V', 'IV', 'IV', 'V, 'claim-text': [{'b': 10', '10', '10', '10', '10', '10, 'sup': IV', 'V, 'claim-text': [{'b': 18', '10', '10', '10', '10', '10', '10', '4', '6, 'sup': IV', 'V, 'has a first end () by which the feeder element (, ′, ″, ′″,, ) is seated on, or arranged with a spacing to, the mould plate () and/or the mould pattern (),'}, {'b': 20', '18', '22', '12', '12', '12', '12', '12, 'sup': 'IV', 'has a second end () which is situated opposite the first end () and which has an assembly element () on which the feeder insert (, ′, ″, ′″,) is arranged,'}, {'b': 24', '24', '26', '26', '18', '20', '24', '28, 'has at least one passage opening (), which extends from the first end to the second end, for the liquid metal, wherein the passage opening () is delimited by a side wall ...

METHOD FOR PRODUCING (4S)-4-[4-CYANO-2-(METHYLSULFONYL)PHENYL]-3,6-DIMETHYL-2-OXO-1-[3-(TRIFLUOROMETHYL)PHENYL]-1,2,3,4-TETRAHYDRO PYRIMIDINE-5-CARBONITRILE

The present invention concerns a new and improved method for preparation of (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluormethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I), as well as the preparation and use of the crystal form (A) of (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluormethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I). 2. The compound of formula (I) in the crystal form (A) , characterized in that the Raman spectrum of the compound shows band maxima at 3075 , 2928 , 2918 , 2236 , 2216 , 1646 , 1605 , 1195 and 1004 cm.3. A method for the preparation of the compound of formula (I) in the crystal form (A) , characterized in that a compound of formula (I) , present in one or more crystal forms or as a solvate , is crystallized out in an alcohol , preferably ethanol , after which the resulting crystal paste is heated to 50-80° C. and further stirred for 2-5 h at this temperature.4. The compound as claimed in one of to for treatment of illnesses.5. The compound as claimed in one of to for use in a method for treatment and/or prevention of diseases of the lungs and the cardiovascular system and for promoting wound healing , especially for chronic wounds.6. The compound as claimed in one of to for use in a method for treatment and/or prevention of pulmonary arterial hypertonia (PAH) and other forms of pulmonary hypertonia (PH) , of chronic obstructive lung diseases (COPD) , of acute lung injury (ALI) , of acute respiratory disease syndrome (ARDS) , of pulmonary emphysema , of alpha-1-antitrypsin deficiency (AATD) , of cystic fibrosis (CF) , of bronchiectasis and to promote wound healing , especially chronic wounds.7. A pharmaceutical containing the compound of formula (I) in the crystal form (A) as claimed in one of to in more than 90 wt. percent referred to the total quantity of the contained compound of formula (I).8. A use of the compound of formula (I) ...

METHOD FOR PRODUCING A MOLDED PART AND FEEDER INSERT FOR USE IN SUCH A METHOD

The invention relates to a method for producing a mold part (′) with a feeder insert arranged in it, with a sprue for liquid metal, for a divisible casting mold for metal casting, with the following steps: 1262626. A method for producing a mold part ( , ′ , ″) with a feeder insert arranged in it , with a sprue for liquid metal , for a divisible casting mold for metal casting , with the following steps:{'b': 26', '26', '26', '2', '2', '2', '28', '2', '2', '2', '28', '26', '26', '26', '10', '10', '30', '30', '30, 'producing or providing a mold part (, ′, ″) equipped with a closed feeder insert (, ′, ″) from a compacted molding material (), the closed feeder insert (, ′, ″) being arranged fixed in place in the compacted molding material () of the mold part (, ′, ″) and having a feeder opening (, ′) connected to regions of a mold cavity (, ′, ″) that is to be formed or has partially formed, and'}{'b': 2', '2', '2', '32', '32', '32, 'opening the closed feeder insert (, ′, ″), so that a sprue (, ′, ″) for liquid metal is formed.'}2262626222. The method as claimed in claim 1 , the production of the mold part ( claim 1 , ′ claim 1 , ″) equipped with the closed feeder insert ( claim 1 , ′ claim 1 , ″) comprising the following steps:{'b': 2', '2', '2, 'arranging the closed feeder insert (, ′, ″) in a molding chamber or a molding box;'}{'b': 28', '2', '2', '2', '28, 'filling molding material () into the molding chamber or the molding box, the closed feeder insert (, ′, ″) being surrounded at least in certain regions by the molding material (), and'}{'b': 28', '26', '26', '26', '2', '2', '2', '28, 'compacting the filled-in molding material (), so that the mold part (, ′, ″) is produced and the closed feeder insert (, ′, ″) is received fixed in place in the compacted molding material ().'}3262626222. The method as claimed in claim 1 , the production of the mold part ( claim 1 , ′ claim 1 , ″) equipped with the closed feeder insert ( claim 1 , ′ claim 1 , ″) comprising the ...

RETAINING DEVICE, AND PIN TO BE PLACED IN A RETAINING DEVICE OF SAID TYPE

The invention relates to a retaining device () comprising a) a holder () that includes a receptacle (), b) a spring-biased pin () which is guided so as to be longitudinally movable in the receptacle () of the holder () and which includes a pin head () that protrudes from the receptacle () of the holder (), c) a centering mechanism () which is stationarily arranged on the pin () and is provided with a restoring force within the receptacle () of the holder (), said restoring force being directed against the holder (). 110. A holding device () , comprising:{'b': 2', '1, 'a) a mounting bracket () with a seat (),'}{'b': 4', '1', '2', '3', '3', '1', '2, 'b) a pin () guided in the seat () of the mounting bracket () in lengthwise displaceable manner, spring-loaded, and having a pin head (), the pin head () extending out from the seat () of the mounting bracket (), and'}{'b': '5', 'c) a centering device (), wherein'}{'b': 5', '4', '1', '2', '2', '5', '6', '7', '8', '4', '6', '7', '8', '4', '1', '2', '18', '19', '2', '18', '19', '6', '7', '8', '4, 'the centering device () is arranged immovably on the pin () and is provided with a restoring force inside the seat () of the mounting bracket () which is directed against the mounting bracket (), and the centering device () comprises at least one tab (, , ), which is disposed substantially equidistant around the periphery of the pin (), on the pin itself, and the at least one tab (, , ) when the pin () is disposed inside the seat () of the mounting bracket () contacts by a contact surface () of an inner wall () of the mounting bracket (), and wherein the contact surface () runs parallel to the inner wall (), and the tab (, , ) is swivelable to produce a restoring force against the pin ().'}254. The holding device according to claim 1 , wherein the centering device () and the pin () are formed of the same material.354. The holding device according to claim 1 , wherein the centering device () and the pin () are fashioned as a single ...

SELECTOR DEVICE

A selector device for a motor vehicle transmission has an actuating lever () transferable into a first shift gate, in which it is coupled mechanically to a transmission component () for actuating a selector control cable (), or into a second shift gate which is decoupled from the transmission component (). The transmission component () is mounted movably, and a locking means () is configured as a spring element that is received in a locking receptacle () when the actuating lever () is situated in the second shift gate. The locking receptacle () has an end centering means (), in which the locking means () is received with a shaped part () when the actuating lever () is situated in the second shift gate, and has a relieving centering means () which tapers conically. The shaped part () is configured to be received in a positively locking manner by the relieving centering means () during move out of the end centering means (). 1. A selector device for a motor vehicle transmission , comprising{'b': '1', 'an actuating lever ()'}{'b': 2', '23, 'a) that is adapted to can be selectively shifted into a first shift gate in which the lever is mechanically coupled to a transmitting component () in order to actuate a gearshift cable () or a gearshift linkage, or'}{'b': '2', 'b) that is adapted to be selectively shifted into a second shift gate in which it is uncoupled from the transmitting component (),'}{'b': '2', 'wherein the transmitting component () is movably supported, and'}{'b': '11', 'wherein a locking means () configured as a spring element is provided,'}{'b': 2', '23', '1, 'c) with which the transmitting component () is adapted to be secured in such a way that the spring element does not exert any force on the gearshift cable () or on the gearshift linkage as long as the actuating lever () has been shifted into the second shift gate, and'}{'b': 16', '1, 'd) for which the locking means is accommodated in a locking receptacle () when the actuating lever () is in the ...

AMIDE-SUBSTITUTED ARYLTRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel 5-(carboxamide)-1-aryl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 6. Compound as defined for use in the treatment and/or prevention of a diseases.7. Compound as defined for use in a method for the treatment and/or prevention of a disease selected from the group consisting ofacute kidney disease,chronic kidney disease,diabetic nephropathy,acute heart failure,chronic heart failure,peripheral arterial disease (PAD),coronary microvascular dysfunction (CMD),Raynaud's syndrome,dysmenorrhea,cardiorenal syndrome,hypervolemic hyponatremia,euvolemic hyponatremia,liver cirrhosis,ascites,edema, andthe syndrome of inadequate ADH secretion (SIADH).8. A method for the manufacture of a pharmaceutical composition for the treatment and/or prevention of a disease selected from the group consisting ofacute kidney disease,chronic kidney disease,diabetic nephropathy,acute heart failure,chronic heart failure,peripheral arterial disease (PAD),coronary microvascular dysfunction (CMD),Raynaud's syndrome,dysmenorrhea,cardiorenal syndrome,hypervolemic hyponatremia,euvolemic hyponatremia,liver cirrhosis,ascites,edema, andthe syndrome of inadequate ADH secretion (SIADH),{'claim-ref': {'@idref': 'CLM-00001', 'claim 1'}, 'the method comprising the step of manufacturing the pharmaceutical composition with the compound of .'}9. Pharmaceutical composition comprising a compound as defined and one or more pharmaceutically acceptable excipients.10. Pharmaceutical composition comprising one or more first active ingredients claim 1 , in particular compounds of general formula (I) according to claim 1 , and one or more further active ingredients.11. The pharmaceutical composition as defined ...

FLUOROALKYL-SUBSTITUTED ARYLTRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel 5-(fluoroalkyl)-1-aryl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 5. The compound of formula (I) according to claim 1 , wherein the compound is selected from the group consisting of5-(4-Chlorophenyl)-2-{[5-(1,1-difluoroethyl)-1-(2-methylphenyl)-1H-1,2,4-triazol-3 yl]methyl}-4-[(2 S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;5-(4-Chlorophenyl)-2-({1-(2,6-dichlorophenyl)-5-[1-fluoroethyl]-1H-1,2,4-triazol-3 yl}methyl)-4-[(2 S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;5-(4-Chlorophenyl)-2-{[1-(2-chlorophenyl)-5-(difluoromethyl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;5-(4-Chlorophenyl)-2-({5-[1-fluoroethyl]-1-(2-methylphenyl)-1H-1,2,4-triazol-3 yl}methyl)-4-[(2 S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;5-(4-Chlorophenyl)-2-({1-(2,6-difluorophenyl)-5-[1-fluoroethyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;5-(4-Chlorophenyl)-2-{[5-(1,1-difluoroethyl)-1-(2,6-difluorophenyl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;5-(4-Chlorophenyl)-2-{[1-(2,6-dichlorophenyl)-5-(1,1-difluoroethyl)-1H-1,2,4-triazol-3-yl]methyl}-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;5-(4-Chlorophenyl)-2-({5-[1-fluoroethyl]-1-(2-methylphenyl)-1H-1,2,4-triazol-3 yl}methyl)-4-[(2 S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one;5-(4-Chlorophenyl)-2-({5-[1-fluoroethyl]-1-[2-(propan-2-yl)phenyl]-1H-1,2,4-triazol-3 yl}methyl)-4-[(2 S)-3,3,3-trifluoro-2-hydroxypropyl ...

HYDROXYALKYL-SUBSTITUTED HETEROARYLTRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel 5-(hydroxyalkyl)-1-heteroaryl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 2. A compound of general formula (I) according to claim 1 , wherein{'sup': '1', 'Rrepresents a methyl group,'} wherein any pyridine group is each optionally substituted, identically or differently, with one or two groups selected from a fluorine atom, a chlorine atom, methoxy, trifluoromethyl and trifluoromethoxy,', 'wherein any pyrazine group is optionally substituted with methoxy,, 'Ar represents a group selected from pyridine, pyrazine, pyridazine, 1-methylimidazole, 1,3-thiazole,'}or a pharmaceutically acceptable salt, hydrate and/or solvate thereof.5. A compound of for treatment and/or prevention of disease.6. A medicament comprising a compound of for use in a method for the treatment and/or prevention of a disease selected from the group consisting ofacute kidney diseasechronic kidney diseasediabetic nephropathy,acute heart failure,chronic heart failure,peripheral arterial disease (PAD),coronary microvascular dysfunction (CMD),Raynaud's syndrome, anddysmenorrhea.8. A pharmaceutical composition comprising a compound as defined in and one or more pharmaceutically acceptable excipients.9. The pharmaceutical composition of comprising one or more first active ingredients.10. The pharmaceutical composition as defined in for the treatment and/or prevention of a disease selected from the group consisting ofacute kidney diseasechronic kidney diseasediabetic nephropathy,acute heart failure,chronic heart failure,peripheral arterial disease (PAD),coronary microvascular dysfunction (CMD),Raynaud's syndrome, anddysmenorrhea.12. Method for the treatment and/or prevention of an acute or ...

AMIDE-SUBSTITUTED PYRIDINYLTRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel 5-(carboxamide)-1-pyridinyl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 5. The compound as defined in for the treatment and/or prevention of a diseases.6. Compound as defined in for use in a method for the treatment and/or prevention of a disease selected from the group consisting ofacute kidney disease,chronic kidney disease,diabetic nephropathy,acute heart failure,chronic heart failure,preeclampsia,peripheral arterial disease (PAD),coronary microvascular dysfunction (CMD),Raynaud's syndrome, anddysmenorrhea.8. Pharmaceutical composition comprising a compound as defined in and one or more pharmaceutically acceptable excipients.9. Pharmaceutical composition of comprising one or more first active ingredients claim 1 , in particular compounds of general formula (I) according to claim 1 , and one or more further active ingredients.10. The pharmaceutical composition as defined in for the treatment and/or prevention of a disease selected from the group consisting ofacute kidney disease,chronic kidney disease,diabetic nephropathy,acute heart failure,chronic heart failure,preeclampsia,peripheral arterial disease (PAD),coronary microvascular dysfunction (CMD),Raynaud's syndrome, anddysmenorrhea. The present invention relates to novel 5-(carboxamide)-1-pyridinyl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.Vasopressin is a neurohormone which basically regulates water homeostasis and ...

Method for producing 5-hydroxyalkyl-substituted 1-phenyl-1,2,4- triazole derivatives

The present application relates to a novel and improved process for preparing 5-(hydroxyalkyl)-1-phenyl-1,2,4-triazole derivatives of the formula (I) in which R 1A and R 1B are independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, ethyl, methoxy, difluoromethoxy and trifluoromethoxy, to novel precursors for preparation thereof, and to the preparation and use of the crystalline polymorph I of (5-(4-chlorophenyl)-2-({1-(3-chlorophenyl)-5-[(1S)-1-hydroxyethyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one of the formula (I-A-1).

SUBSTITUTED TRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 2. A compound of formula (I) according to claim 1 , wherein{'sup': '1', 'Rrepresents hydrogen or methyl,'}{'sup': '2', 'sub': 1', '5, 'claim-text': [{'sub': 3', '6, 'claim-text': wherein oxetan-3-yl may be substituted by one substituent methyl,', 'and', 'wherein cycloalkyl may be substituted by one substituent hydroxyl,, 'where alkyl may be substituted by 1 to 2 substituents independently of one another selected from the group consisting of hydroxy, amino, trifluoromethyl, methoxy, C-C-cycloalkyl and oxetan-3-yl,'}, 'and', 'where pyrrolidin-3-yl may be substituted by one substituent formyl,, 'Rrepresents amino, C-C-alkyl, methoxy, cyclopropyl or pyrrolidin-3-yl,'}or{'sup': 1', '2, 'claim-text': {'sub': 1', '4, 'where pyrrolidinyl, piperazinyl and morpholinyl may be substituted by 1 to 3 substituents independently of one another selected from the group consisting of oxo, hydroxy, methyl, trifluoromethyl and C-C-alkoxycarbonyl,'}, 'Rand Rtogether with the nitrogen atom to which they are attached form a pyrrolidinyl, piperazinyl or morpholinyl,'}{'sup': '3', 'claim-text': where phenyl may be substituted by one substituent selected from the group consisting of chlorine, fluorine, methoxy and trifluoromethyl,', 'and', 'where pyridinyl may be substituted by one substituent selected from the group consisting of chlorine, bromine, methoxy, trifluoromethyl and trifluoromethoxy,, 'Rrepresents phenyl, pyridinyl or 3,3,3-trifluoroprop-1-yl,'}and/or a pharmaceutically acceptable salt thereof, solvate thereof and/or solvate of a salt thereof.3. A compound of formula (I) according to claim 1 , wherein{'sup': '1', ...

AMIDE-SUBSTITUTED PHENYLTRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel 5-(carboxamide)-1-phenyl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 5. The compound as defined in for use in the treatment and/or prevention of a diseases.6. The compound as defined in for use in a method for the treatment and/or prevention ofacute kidney disease,chronic kidney disease,diabetic nephropathy,acute heart failure,chronic heart failure,preeclampsia,peripheral arterial disease (PAD),coronary microvascular dysfunction (CMD),Raynaud's syndrome, anddysmenorrhea.8. Pharmaceutical composition comprising a compound as defined in and one or more pharmaceutically acceptable excipients.9. Pharmaceutical composition comprising one or more first active ingredients claim 1 , in particular compounds of general formula (I) according to claim 1 , and one or more further active ingredients.10. The pharmaceutical composition as defined in for the treatment and/or prevention of a disease selected from the group consisting ofacute kidney disease,chronic kidney disease,diabetic nephropathy,acute heart failure,chronic heart failure,preeclampsia,peripheral arterial disease (PAD),coronary microvascular dysfunction (CMD),Raynaud's syndrome, anddysmenorrhea.13. The pharmaceutical composition of wherein the one or more further active ingredients is selected from the group consisting ofdiuretic,angiotensin AII antagonist,ACE inhibitor,beta-receptor blocker,mineralocorticoid receptor antagonist,antidiabetic,organic nitrate,NO donor,activator, andstimulator of the soluble guanylate cyclase,antiinflammatory agents,immunosuppressive agent,phosphate binder, andcompound which modulate vitamin D metabolism. The present invention relates to novel 5-(carboxamide)-1-phenyl-1,2, ...

INHIBITOR OF THE MUTATED ISOCITRATE DEHYDROGENASE IDH1 R132H

The present invention relates to the adduct (2E)-but-2-enedioic acid-3-(2-{[4-(trifluoromethoxy)phenyl]amino}-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]-1H-benzimidazol-yl)propanoic acid (1:4), methods for preparing this adduct, pharmaceutical compositions comprising this adduct and also the use of this adduct for preparing a medicament for the treatment of a disease. 1. An adduct which is (2E)-But-2-enedioic acid-3-(2-{[4-(trifluoromethoxy)phenyl]amino }-1-[(1R ,5R)-3 ,3 ,5-trimethylcyclohexyl]-1H-benzimidazol-5-yl)propanoic acid (1:4).2. The adduct according to in crystalline form claim 1 , characterized by maxima in the X-ray diffractogram at the following 2 theta angles: 5.4 claim 1 , 6.8 claim 1 , 10.2 claim 1 , 10.3 claim 1 , 10.8 claim 1 , 11.1 claim 1 , 16.8 claim 1 , and 21.6.3. The adduct according to in crystalline form claim 1 , characterized by maxima in the Raman spectrum at the following wavenumbers in units of cm: 3088 claim 1 , 3047 claim 1 , 2934 claim 1 , 2910 claim 1 , 2874 claim 1 , 2771 claim 1 , 2717 claim 1 , 1658 claim 1 , 1632 claim 1 , 1615 claim 1 , 1521 claim 1 , 1463 claim 1 , 1451 claim 1 , 1420 claim 1 , 1338 claim 1 , 1306 claim 1 , 1294 claim 1 , 1277 claim 1 , 1245 claim 1 , 1198 claim 1 , 1184 claim 1 , 1167 claim 1 , 1155 claim 1 , 1127 claim 1 , 1109 claim 1 , 1077 claim 1 , 1049 claim 1 , 1018 claim 1 , 979 claim 1 , 961 claim 1 , 943 claim 1 , 922 claim 1 , 908 claim 1 , 877 claim 1 , 866 claim 1 , 839 claim 1 , 817 claim 1 , 789 claim 1 , 767 claim 1 , 714 claim 1 , 700 claim 1 , 685 claim 1 , 646 claim 1 , 631 claim 1 , 613 claim 1 , 568 claim 1 , 517 claim 1 , 503 claim 1 , 450 claim 1 , 438 claim 1 , 416 claim 1 , 388 claim 1 , 358 claim 1 , 339 claim 1 , 330 claim 1 , and 102.4. A method for preparing the adduct according to claim 1 , comprising the steps of:introducing 3-(2-{[4-(trifluoromethoxy)phenyl]amino}-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]-1H-benzimidazol-5-yl)propanoic acid and (2E)-but-2-enedioic acid in isopropanol, ...

METHOD FOR PREPARING SUBSTITUTED 3-(2-ANILINO-1-CYCLOHEXYL-1H-BENZIMIDAZOL-5-YL)PROPANOIC ACID DERIVATIVES

The present invention relates to a method for preparing substituted 3-(2-anilino-1-cyclohexyl-1H-benzimidazol-5-yl)propanoic acid derivatives of the general formula (I) in which Rrepresents a hydrogen atom or Rrepresents a group selected from the series of C-C-alkyl-, C-C-alkoxy-, C-C-haloalkyl- and C-C-haloalkoxy-, Rrepresents a hydrogen atom or a C-C-alkyl group, Rrepresents a hydrogen atom or a C-C-alkyl group, Rrepresents a cyclohexyl group, which is optionally singly or multiply substituted by a C-C-alkyl group, and Rrepresents a hydrogen atom or a C-C-alkyl group; and also intermediates which may be used to prepare substituted 3-(2-anilino-1-cyclohexyl-1H-benzimidazol-5-yl)propanoic acid derivatives. The present invention also relates to a crystalline form of 3-(2-{[4-(trifluoromethoxy)phenyl]amino}-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]-1H-benzimidazol-5-yl)propanoic acid, pharmaceutical compositions comprising this crystalline form, and also the use of this crystalline form for preparing a medicament for the treatment of a disease. 2. The method according to claim 1 , wherein Ris a hydrogen atom claim 1 , Ris a hydrogen atom and Rrepresents a group selected from the group consisting of C-C-alkyl- claim 1 , C-C-alkoxy- claim 1 , C-C-haloalkyl- and C-C-haloalkoxy-.3. The method according to claim 1 , wherein Ris a hydrogen atom claim 1 , Ris a hydrogen atom and Rrepresents a group selected from the group consisting of methyl- claim 1 , methoxy- claim 1 , trifluoromethyl- and trifluoromethoxy-.5. The method according to claim 1 , wherein Rrepresents a hydrogen atom or a methyl group.9. The method according to for preparing 3-(2-{[4-(trifluoromethoxy)phenyl]amino}-1-[(1R claim 1 ,5R)-3 claim 1 ,3 claim 1 ,5-trimethylcyclohexyl]-1H-benzimidazol-5-yl)propanoic acid comprising the following steps:(a) reacting an alkyl ester of 3-(4-fluoro-3-nitrophenyl)propanoic acid with (1R,5R)-3,3,5-trimethylcyclohexanamine to give an alkyl ester of 3-(3-nitro-4-{[(1R,5R)-3,3,5- ...

SUBSTITUTED TRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 5. Compound for use as defined in for the treatment and/or prevention of diseases.6. Compound as defined in for use in a method for the treatment and/or prevention of acute and chronic kidney diseases including diabetic nephropathy claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome claim 1 , dysmenorrhea claim 1 , cardiorenal syndrome claim 1 , hypervolemic and euvolemic hyponatremia claim 1 , liver cirrhosis claim 1 , ascites claim 1 , edema and the syndrome of inadequate ADH secretion (SIADH).7. A product comprising a compound as defined in for the manufacture of a pharmaceutical composition for the treatment and/or prevention of acute and chronic kidney diseases including diabetic nephropathy claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome dysmenorrhea claim 1 , cardiorenal syndrome claim 1 , hypervolemic and euvolemic hyponatremia claim 1 , liver cirrhosis claim 1 , ascites claim 1 , edema and the syndrome of inadequate ADH secretion (SIADH).8. Pharmaceutical composition comprising a compound as defined in and one or more pharmaceutically acceptable excipients.9. Pharmaceutical composition of comprising one or more first active ingredients claim 8 , optionally compound of formula (I) claim 8 , and one or more further active ingredients claim 8 , optionally one or more additional therapeutic agents selected from the group ...

DEVICE FOR DETECTING THE POSITION OF A GEAR STEP SELECTOR LEVER

The invention relates to a device for detecting the position of a gearshift lever for selecting a gear/driving stage or a gear setting of a motor vehicle. The device has a signal transmitter installed on the gearshift lever and a signal receiver installed at a distance from the signal transmitter, wherein it is possible to detect the different positions of the signal transmitter relative to the signal receiver in different gears or gear settings. The invention further relates to a motor vehicle having such a device. 1101. A device () for detecting the position of a gearshift lever () that serves to select a gear setting of a motor vehicle , having comprising:{'b': 2', '1, 'at least one signal transmitter () installed on the gearshift lever (); and'}{'b': 3', '2', '2', '3', '1', '2', '3, 'at least one signal receiver () installed at a distance from the signal transmitter (), wherein the position of the signal transmitter () relative to the signal receiver () differs in different selectable gears, so that when the gearshift lever () is actuated to switch over from a shift gate function to a touch shift gate function or vice versa, the signal transmitter () only executes a translatory movement relative to the signal receiver ().'}21024. The device () according to claim 1 , wherein the signal transmitter () is installed so that it is movable in a linear guide ().31051217517. The device () according to claim 1 , further comprising: an actuation element () to transmit the movement of the gearshift lever () to the signal transmitter () claim 1 , wherein the gearshift lever () has a tilting axis () and said actuation element () engages with the gearshift lever () outside of its tilting axis ().4102645. The device () according to claim 1 , wherein the signal transmitter () is accommodated in a receptacle () that that is movable linearly in the linear guide () and operatively connected to the actuation element ().510289. The device () according to claim 1 , wherein linear ...

AMIDE-SUBSTITUTED PYRIDINYLTRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel 5-(carboxamide)-1-pyridinyl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 3. The compound as defined in for use in a method for treatment of at least one selected from the group consisting of acute and chronic kidney diseases claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome claim 1 , and dysmenorrhea.4. Compound as defined in for use in a method for treatment of diabetic nephropathy.5. Pharmaceutical composition comprising a compound as defined in claim 1 , and one or more pharmaceutically acceptable excipients.6. Pharmaceutical composition of comprising one or more first active ingredients claim 4 , which are compounds of general formula (I) claim 4 , and one or more further active ingredients claim 4 , which are one or more additional therapeutic agents selected from the group consisting of diuretics claim 4 , angiotensin AII antagonists claim 4 , ACE inhibitors claim 4 , beta-receptor blockers claim 4 , mineralocorticoid receptor antagonists claim 4 , antidiabetics claim 4 , organic nitrates and NO donors claim 4 , activators and stimulators of the soluble guanylate cyclase (sGC) claim 4 , antiinflammatory agents claim 4 , immunosuppressive agents claim 4 , phosphate binders claim 4 , and/or compounds that modulate vitamin D metabolism.7. The pharmaceutical composition as defined in for treatment of at least one selected from the group consisting of acute kidney disease claim 4 , chronic kidney disease claim 4 , acute heart failure claim 4 , chronic heart failure claim 4 , preeclampsia claim 4 , peripheral arterial ...

METHOD FOR PRODUCING (4S)-4-[4-CYANO-2-(METHYLSULFONYL)PHENYL]-3,6-DIMETHYL-2-OXO-1-[3-(TRIFLUOROMETHYL)PHENYL]-1,2,3,4-TETRAHYDRO PYRIMIDINE-5-CARBONITRILE

The invention relates to a new and improved method for preparation of (4S)-4-[4-cyano-2-(methyl sulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I), as well as the preparation and use of the crystal form (A) of (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I). 2. The method of claim 1 , wherein the cinchona alkaloid is chosen from the group consisting of quinine and quinidine.3. The compound of wherein Rin the compound of formulas (XXVI) claim 1 , (XXVII) claim 1 , (XXVIII) and (XXIX) is hydrogen.4. The compound of wherein Rin the compound of formulas (XXVI) claim 1 , (XXVII) claim 1 , (XXVIII) and (XXIX) is methyl.6. The compound of wherein Ris hydrogen.7. The compound of wherein Ris methyl.8. The compound of as the quinidine salt. This divisional application claims the benefit of priority to U.S. application Ser. No. 15/559,385, filed 18 Sep. 2017, which is a Section 371 application of International Application No. PCT/EP2016/055498, filed 15 Mar. 2016, which claims the benefit of priority to European Patent Application No. 15159570.9, filed 18 Mar. 2015, all of which are herein incorporated by reference in their entirety.The invention relates to a novel and improved method for producing (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I), and to the production and use of the crystal form (A) of (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I).Method for producing (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrileThe present invention relates to improved methods for producing (4S)-4-[4-cyano-2-(methylsulfonyl) ...

Amine substituted triazole derivatives and uses thereof

The present invention relates to novel amine substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

SUBSTITUTED TRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 2. A compound of according to claim 1 , wherein{'sup': '1', 'claim-text': where methyl is substituted by one substituent selected from the group consisting of trifluoromethyl, methoxy and methylsulfonyl,', 'and', 'where ethyl is substituted by one substituent trifluoromethyl,, 'Rrepresents methyl, ethyl, 3,3,3-trifluoro-prop-1-en-1-yl, 1-trifluoromethylcycloprop-1-yl, 2,2-difluorocycloprop-1-yl, 4-fluoropyrrolidin-2-yl, 5-oxopyrrolidin-2-yl, 1,1-dioxo-thietan-3-yl or 5-chloro-thiophen-2-yl,'}{'sup': '2', 'Rrepresents chlorine or trifluoromethyl,'}And/or a pharmaceutically acceptable salt thereof, solvate thereof and/or solvate of a salt thereof.3. A compound of according to claim 1 , wherein{'sup': '1', 'claim-text': where methyl is substituted by one substituent methylsulfonyl,', 'and', 'where ethyl is substituted by one substituent trifluoromethyl,, 'Rrepresents methyl, ethyl, 2,2-difluorocycloprop-1-yl, 4-fluoropyrrolidin-2-yl or 5-oxopyrrolidin-2-yl,'}{'sup': '2', 'Rrepresents chlorine,'}And/or a pharmaceutically acceptable salt thereof, solvate thereof and/or solvate of a salt thereof.5. Compound as defined in for treatment and/or prevention of one or more diseases.6. Compound as defined in for treatment and/or prevention of one or more acute and chronic kidney diseases optionally including one or more of diabetic nephropathy claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome claim 1 , dysmenorrhea claim 1 , cardiorenal syndrome claim 1 , hypervolemic and ...

SYNTHESIS OF COPANLISIB AND ITS DIHYDROCHLORIDE SALT

The present invention relates to a novel method of preparing copanlisib, copanlisib dihydrochloride, or hydrates of copanlisib dihydrochloride, to novel intermediate compounds, and to the use of said novel intermediate compounds for the preparation of said copanlisib, copanlisib dihydrochloride, or hydrates of copanlisib dihydrochloride. The present invention also relates to copanlisib dihydrochloride hydrates as compounds. 10: The method according to claim 8 , wherein said copanlisib dihydrochloride (11) is in the form of copanlisib dihydrochloride hydrate I.11: The method according to claim 8 , wherein said copanlisib dihydrochloride (11) is in the form of copanlisib dihydrochloride hydrate II.12: Copanlisib dihydrochloride hydrate I claim 8 , as prepared by the method according to .13: Copanlisib dihydrochloride hydrate II claim 8 , as prepared by the method according to .14: Copanlisib dihydrochloride hydrate I.15: Copanlisib dihydrochloride hydrate I of claim 14 , having an XRPD peak maximum [°2Θ] (Copper (Cu)) of 5.6.16: Copanlisib dihydrochloride hydrate I of claim 14 , having an XRPD peak maximum [°2Θ] (Copper (Cu)) of 7.0.17: Copanlisib dihydrochloride hydrate I of claim 14 , having an XRPD peak maximum [°2Θ] (Copper (Cu)) of 15.4.18: Copanlisib dihydrochloride hydrate I of claim 14 , having an XRPD peak maximum [°2Θ] (Copper (Cu)) of 26.4.19: Copanlisib dihydrochloride hydrate I of claim 14 , having an XRPD peak maxima [°2Θ] (Copper (Cu)) of 5.6 claim 14 , 7.0 claim 14 , 15.4 and 26.4.20: Copanlisib dihydrochloride hydrate II.21: Copanlisib dihydrochloride hydrate II of claim 20 , having an XRPD peak maximum [°2Θ] (Copper (Cu)) of 5.7.22: Copanlisib dihydrochloride hydrate II of claim 20 , having an XRPD peak maximum [°2Θ] (Copper (Cu)) of 7.3.23: Copanlisib dihydrochloride hydrate II of claim 20 , having an XRPD peak maxima [°2Θ] (Copper (Cu)) of 5.7 and 7.3. The present invention relates to a novel method of preparing 2-amino-N-[7-methoxy-8-(3-morpholin- ...

METHOD FOR PRODUCING 5-HYDROXYALKYL-SUBSTITUTED 1-PHENYL-1,2,4- TRIAZOLE DERIVATIVES

The present application relates to a novel and improved process for preparing 5-(hydroxyalkyl)-1-phenyl-1,2,4-triazole derivatives of the formula (I) 2. A pharmaceutical composition comprising the crystalline form of the polymorph I according to of any other form of the compound of the formula (I-A-1).3. A pharmaceutical composition comprising the crystalline form of the polymorph I according to in more than 90% by weight based on the total amount of the compound of the formula (I-A-1) present.4. A method for producing a pharmaceutical composition for treatment of cardiovascular disorders or renal disorders claim 1 , the method comprising the step of mixing the crystalline form of the polymorph I of with at least one pharmaceutically acceptable carrier.5. A method of treating a cardiovascular disorder or a renal disorder comprising administering an effective amount of a crystalline form of the polymorph I according to .6. A process for preparing the compound (5-(4-chlorophenyl)-2-({1-(3-chlorophenyl)-5-[(1S)-1-hydroxyethyl]-1H-1 claim 1 ,2 claim 1 ,4-triazol-3-yl}methyl)-4-[(2S)-3 claim 1 ,3 claim 1 ,3-trifluoro-2-hydroxypropyl]-2 claim 1 ,4-dihydro-3H-1 claim 1 ,2 claim 1 ,4-triazol-3-one of the formula (I-A-1) in crystalline form of polymorph I claim 1 , the process comprisingstirring the compound of the formula (I-A-1), in a mixture of methyl tert-butyl ether/diisopropyl ether or of methyl tert-butyl ether/n-heptane at a temperature of 20° C. to 80° C., wherein the compounds is optionally present in one or more polymorphs or in solvate formfiltering the compound;washing the compound;drying the compound under reduced pressure.9. The compound of wherein Ris methyl. This application is a Divisional application of U.S. patent application Ser. No. 16/098,238, filed 1 Nov. 2018, which is a National Stage entry of International Application No. PCT/EP2017/060367, filed 2 May 2017, which claims priority to European Patent Application No. 17160086.9, filed 9 Mar. 2017 and ...

AMIDE-SUBSTITUTED PYRIDINYLTRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel 5-(carboxamide)-1-pyridinyl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 5. Compound for use as defined in for the treatment and/or prevention of diseases.6. Compound as defined in for use in a method for the treatment and/or prevention of acute and chronic kidney diseases including diabetic nephropathy claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome and dysmenorrhea.7. Use of a compound as defined in for the manufacture of a pharmaceutical composition for the treatment and/or prevention of acute and chronic kidney diseases including diabetic nephropathy claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome claim 1 , and dysmenorrhea.8. Pharmaceutical composition comprising a compound as defined in claim 1 , and one or more pharmaceutically acceptable excipients.9. Pharmaceutical composition of comprising one or more first active ingredients claim 8 , in particular compounds of general formula (I) claim 8 , and one or more further active ingredients claim 8 , in particular one or more additional therapeutic agents selected from the group consisting of diuretics claim 8 , angiotensin AII antagonists claim 8 , ACE inhibitors claim 8 , beta-receptor blockers claim 8 , mineralocorticoid receptor antagonists claim 8 , antidiabetics claim 8 , organic nitrates and NO donors claim 8 , activators and stimulators of the soluble guanylate cyclase (sGC) claim 8 , antiinflammatory agents claim 8 ...

Hydroxyalkyl-substituted triazole derivatives and uses thereof

The present invention relates to novel 3-(hydroxyalkyl)-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and/or cardiovascular diseases.

SUBSTITUTED TRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 7. The compound as defined in for treatment and/or prevention of one or more diseases.8. The compound as defined in for treatment and/or prevention of acute and chronic kidney disease comprising one or more of diabetic nephropathy claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome claim 1 , dysmenorrhea claim 1 , cardiorenal syndrome claim 1 , hypervolemic and euvolemic hyponatremia claim 1 , liver cirrhosis claim 1 , ascites claim 1 , edema and the syndrome of inadequate ADH secretion (SIADH).9. The compound as defined in for manufacture of a pharmaceutical composition for treatment and/or prevention of acute and chronic kidney disease comprising one or more of diabetic nephropathy claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome dysmenorrhea claim 1 , cardiorenal syndrome claim 1 , hypervolemic and euvolemic hyponatremia claim 1 , liver cirrhosis claim 1 , ascites claim 1 , edema and the syndrome of inadequate ADH secretion (SIADH).10. Pharmaceutical composition comprising a compound as defined in and one or more pharmaceutically acceptable excipients.11. Pharmaceutical composition of comprising one or more first active ingredients claim 10 , optionally a compound of formula (I) claim 10 , and one or more further active ingredients claim 10 , optionally one or more additional therapeutic agents selected from the group ...

SHIFTING DEVICE FOR AN AUTOMATIC GEARBOX

The invention relates to a shifting device for a transmission, especially an automatic transmission of a motor vehicle, having an actuating lever that can be moved into different positions in order to select gears, and having a movably mounted transmission component that serves to transmit movements of the actuating lever to at least one additional component, especially a control cable, whereby the actuating lever can be either coupled to or uncoupled from the transmission component. The shifting device is characterized in that, in order to effectuate the coupling, a projection of the actuating lever engages into a receptacle that is movably mounted on and/or in the transmission component. Alternatively or additionally, the shifting device is characterized in that, in order to effectuate the coupling, a projection of the transmission component engages into a receptacle that is movably mounted on and/or in the actuating lever. 1. A shifting device for an automatic transmission of a motor vehicle , comprising:an actuating lever adapted to be moved into different positions in order to select gears;a projection extending from a surface of the actuating lever; anda movably mounted transmission component that serves to transmit movements of the actuating lever to at least another component, such as a control cable;wherein the actuating lever is adapted to be either coupled to or uncoupled from the transmission component; andin order to effectuate the coupling, the projection of the actuating lever engages into a receptacle that is movably mounted on or in the transmission component.2. The shifting device according to claim 1 , wherein the receptacle is mounted so as to be movable against the force of a spring element relative to the actuating lever or relative to the transmission component.3. The shifting device according to claim 2 , wherein the spring element has a leaf spring.4. The shifting device according to whereinthe transmission component has a recess in which ...

PRODRUGS OF SUBSTITUTED TRIAZOLE DERIVATIVES AND USES THEREOF

The present invention relates to prodrugs of 3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1-[3-(trifluoromethyl)-pyridin-2-yl]-1H-1,2,4-triazole-5-carboxamide, 3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1-[2-(trifluoromethyl)-phenyl]-1H-1,2,4-triazole-5-carboxamide and 3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1-(3-chloropyridin-2-yl)-1H-1,2,4-triazole-5-carboxamide, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 6. Compound as defined in to for treatment and/or prevention of one or more diseases.7. Compound as defined in for treatment and/or prevention of one or more acute and/or chronic kidney diseases including diabetic nephropathy claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome claim 1 , dysmenorrhea claim 1 , cardiorenal syndrome claim 1 , hypervolemic and euvolemic hyponatremia claim 1 , liver cirrhosis claim 1 , ascites claim 1 , edema and the syndrome of inadequate ADH secretion (SIADH).8. A product comprising a compound as defined in or a composition thereof for treatment and/or prevention of one or more acute and chronic kidney diseases including diabetic nephropathy claim 1 , acute and chronic heart failure claim 1 , preeclampsia claim 1 , peripheral arterial disease (PAD) claim 1 , coronary microvascular dysfunction (CMD) claim 1 , Raynaud's syndrome dysmenorrhea claim 1 , cardiorenal syndrome claim 1 , hypervolemic and euvolemic hyponatremia claim 1 , liver cirrhosis ...

Substituted bis-aryl pyrazole amides having terminal primary amide functionalization for treating retroviral diseases

The present invention relates to novel substituted bis-aryl pyrazole amides, to methods for the production thereof, to the use thereof for the treatment and/or prophylaxis of illnesses, and to the use thereof for producing pharmaceuticals for retroviral diseases, in humans and/or animals. The compounds are particularly effective against HIV.

Substituted bis-arylpyrazolamides with terminal primary amide functionality and their use

Die vorliegende Erfindung betrifft neue substituierte Bis-Arylpyrazolamide, Verfahren zu ihrer Herstellung, ihre Verwendung zur Behandlung und/oder Prophylaxe von Krankheiten sowie ihre Verwendung zur Herstellung von Arzneimitteln zur Behandlung und/oder Prophylaxe von Krankheiten, insbesondere von retroviralen Erkrankungen, bei Menschen und/oder Tieren.

Vertically divided feeder for being used when pouring metals into casting moulds, and method for the production thereof

The invention relates to a feeder insert (1, 1', 1'', 1''', 100, 100') for being used when pouring metals into casting moulds, comprising a feeder body (2, 2', 2'', 2''', 102, 102'), which delimits a feeder cavity (4, 4', 4'', 4''', 104, 104') for receiving liquid metal, wherein the feeder body (2, 2', 2'', 2''', 102, 102') has a first end (6, 6', 6'', 6''', 106, 106') with a passage opening (8) for the liquid metal and a second end (10, 10', 10'', 10''', 110, 110'), opposite the first end (6, 6', 6'', 6''', 106, 106'), and wherein the feeder body (2, 2', 2'', 2''', 102, 102') has a central axis (Z) extending through the passage opening (8). The feeder body (2, 2', 2'', 2''', 102, 102') is separated at at least one dividing plane (E), extending in the direction of the central axis (Z), and is formed by at least a first feeder shell (18, 18', 18'', 18''', 118, 118') and a second feeder shell (20, 20', 20'', 20''', 120, 120'). The first and second feeder shells (18, 18', 18'', 18''', 118, 118') are connected to one another to form the feeder body (2, 2', 2'', 2''', 102, 102').

Arrangement for use in producing a divisible mold

Beschrieben wir eine Anordnung zur Verwendung beim Herstellen einer teilbaren Gießform, vorzugsweise einer vertikal teilbaren Gießform, umfassend: (i) eine Formplatte (4, 4‘) und/oder ein Formmodell (6), (ii) ein Speisersystem (8, 8‘, 8‘‘, 8‘‘‘, 8IV, 8V) mit einem Speiserelement (10, 10‘, 10‘‘, 10‘‘‘, 10IV, 10V) und einem Speisereinsatz (12, 12‘, 12‘‘, 12‘‘‘, 12IV), wobei Speiserelement (10, 10‘, 10‘‘, 10‘‘‘, 10IV, 10V) und Speisereinsatz einen Speiser-Hohlraum (14) zur Aufnahme flüssigen Metalls begrenzen, wobei das Speiserelement (10, 10‘, 10‘‘, 10‘‘‘, 10IV, 10V) – ein erstes Ende (18) besitzt, mit dem das Speiserelement (10, 10‘, 10‘‘, 10‘‘‘, 10IV, 10V) auf der Formplatte (4) und/oder dem Formmodell (6) aufsitzt oder mit Abstand dazu angeordnet ist, – ein dem ersten Ende (18) gegenüberliegendes zweites Ende (20) mit einem Montageelement (22) besitzt, an dem der Speisereinsatz (12, 12‘, 12‘‘, 12‘‘‘, 12IV) angeordnet ist, – mindestens eine sich vom ersten Ende zum zweiten Ende erstreckende Durchtrittsöffnung (24) für das flüssige Metall aufweist, wobei die Durchtrittsöffnung (24) von einer Seitenwand (26, 26‘) begrenzt wird, wobei die Seitenwand zur Verringerung des Abstands zwischen dem ersten und zweiten Ende (18, 20) verformbar ist, und wobei die Durchtrittsöffnung (24) eine Öffnungsachse (28) aufweist, wobei der Speiser-Hohlraum (14) einen relativ zur Öffnungsachse (28) versetzten Volumenschwerpunkt hat, wobei die Anordnung zusätzlich umfasst, ein oder mehrere Kippsicherungselemente (30, 30‘, 30‘‘, 32, 32‘, 32‘‘, 32‘‘‘), die dazu eingerichtet sind, einem Verkippen des Speisersystems (8, 8‘, 8‘‘, 8‘‘‘, 8IV, 8V) um das erste Ende (18) des Speiserelements (10, 10‘, 10‘‘, 10‘‘‘, 10IV, 10V) aus der Öffnungsachse (28) heraus entgegenzuwirken, wenn bei Beaufschlagung des Speisersystems mit einer parallel zur Öffnungsachse (28) und in Richtung des ersten Endes (18) des Speiserelements wirkenden Kraft die Seitenwand (26, 26‘) verformt und der Abstand zwischen dem ersten ...

Trimmed macrocyclic substituted benzene derivatives

Metallkompleksene med den generelle formel (I), hvori Hal står for brom eller jod og Aog A2 har forskjellige betydninger, er egnede som kontrastmidler.

Substituted triazole derivatives and uses thereof

The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 5

Method for preparing substituted 3-(2-anilino-1-cyclohexyl-1h-benzimidazol-5-yl)propanoic acid derivatives

The present invention relates to a method for preparing substituted 3-(2-anilino-1-cyclohexyl-1H-benzimidazol-5-yl)propanoic acid derivatives of the general formula (I) in which R1 represents a hydrogen atom or R1 represents a group selected from the series of C1-C3-alkyl-, C1-C3-alkoxy-, C1-C3-haloalkyl- and C1-C3-haloalkoxy-, R2 represents a hydrogen atom or a C1-C3-alkyl group, R3 represents a hydrogen atom or a C1-C3-alkyl group, R4 represents a cyclohexyl group, which is optionally singly or multiply substituted by a C1-C3-alkyl group, and R5 represents a hydrogen atom or a C1-C6-alkyl group; and also intermediates which may be used to prepare substituted 3-(2-anilino-1- cyclohexyl-1H-benzimidazol-5-yl)propanoic acid derivatives. The present invention also relates to a crystalline form of 3-(2-{[4-(trifluoromethoxy)phenyl]amino}-1-[(1R,5R)-3,3,5- trimethylcyclohexyl]-1H-benzimidazol-5-yl)propanoic acid, pharmaceutical compositions comprising this crystalline form, and also the use of this crystalline form for preparing a medicament for the treatment of a disease.

Substituted triazole derivatives and uses thereof

The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases. 5

Substituted triazole derivatives and uses thereof

Substituted triazole derivatives and uses thereof The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

Method for producing (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile

The invention relates to a novel and improved method for producing (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I), and to the production and use of the crystal form (A) of (4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile of formula (I).

Metal chelates having a perfluorinated peg radical, processes for their preparation, and their use

The invention relates to the subjects characterized in the patent claims, namely metal chelates having a perfluorinated PEG radical, processes for their preparation, and their use, processes for their preparation and their use in NMR and X-ray diagnosis, radiodiagnosis and radiotherapy, and in MRT lymphography.

Substituted triazole derivatives and uses thereof

The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

CONJUGATES OF MACRO CYCLIC METALLIC COMPLEXES WITH BIOMOLECULES AND PREPARATION OF DIAGNOSTIC MEDIA CONTAINING THEM FOR NUCLEAR MAGNETIC RESONANCE, RADIODIAGNOSIS AND RADIOTHERAPYARADIODIAGNOSTIC AND RADIOTHERAPY

CONJUGADOS DE FORMULA (I), DONDE Z ES H O AL MENOS DOS Z SON UN EQUIVALENTE DE UN ION METALICO; B ES H O UN RADICAL ALQUILO C1-4; R ES H O UN RADICAL ALQUILO C1-10 O ARILO LINEAL RAMIFICADO O CICLICO, SATURADO O INSATURADO SUSTITUIDO OPCIONALMENTE POR UN GRUPO CARBOXILO, -SO3H o -PO3H2; DONDE, LA CADENA C1-10 CONTIENE UN GRUPO ARILO Y/O 1 A 2 ATOMOS DE OXIGENO Y LOS RADICALES B Y R NO REPRESENTAN AL MISMO TIEMPO ATOMOS DE OXIGENO; A ES UNA CADENA DE HIDROCARBUROS C1-30 LINEAL O RAMIFICADA, SATURADA O INSATURADA, QUE TIENE OPCIONALMENTE 1 A 5 ATOMOS DE OXIGENO, 1 A 5 ATOMOS DE NITROGENO Y/O 1 A 5 RADICALES -NR´, DONDE R´ ESTA DEFINIDO COMO R, PERO PUEDE SELECCIONARSE DE MODO INDEPENDIENTE, QUE ESTA OPCIONALMENTE SUSTITUIDO CON 1 A 3 GRUPOS CARBOXILO, 1 A 3 -SO3H, 1 A 3 -PO3H2 Y/O 1 A 3 ATOMOS DE HALOGENO, DONDE ESTAN PRESENTES OPCIONALMENTE 1 A 3 ATOMOS DE C, COMO GRUPOS CARBONILO, ESTANDO A O UNA PARTE DE A DISPUESTA EN FORMA DE ANILLO Y CONFORMADA DE MODO TAL QUE X´ ESTA ENLAZADO A TRAVES DE 3 ATOMOS CON EL ATOMO DE NITROGENO AL QUE ESTA UNIDO A; X´ ES EL RADICAL DE UN GRUPO X QUE REACCIONO CON UNA BIOMOLECULA; Y, Bio ES EL RADICAL DE UNA BIOMOLECULA, SUS SALES CON LA CONDICION DE QUE CUANDO B ES H Y R ES C1-4, A NO ES EL RADICAL DE FOMULA (II), SIENDO R3 UN ATOMO DE H O UN RADICAL ALQUILO C1-4; D ES ALQUILENO C1-4 LINEAL O RAMIFICADO, SATURADO O INSATURADO QUE PUEDE SER SUSTITUIDO POR UN GRUPO CARBONILO Y D ESTA UNIDO A X CONJUGATES OF FORMULA (I), WHERE Z IS H OR AT LEAST TWO Z ARE AN EQUIVALENT OF A METALLIC ION; B IS H O A RADICAL C1-4 ALKYL; R IS H OR A C1-10 RADICAL ALKYL OR BRANCHED OR CYCLIC LINEAR ARYL, SATURATED OR UNSATURATED, OPTIONALLY REPLACED BY A CARBOXYL GROUP, -SO3H or -PO3H2; WHERE, CHAIN C1-10 CONTAINS AN ARYL GROUP AND / OR 1 TO 2 OXYGEN ATOMS AND THE B AND R RADICALS DO NOT REPRESENT OXYGEN ATOMS AT THE SAME TIME; A IS A C1-30 LINEAR OR BRANCHED HYDROCARBON CHAIN, SATURATED OR UNSATURATED, WHICH OPTIONALLY HAS 1 TO 5 OXYGEN ATOMS, 1 TO 5 ...

Substituted triazole derivatives and uses thereof

Substituted triazole derivatives and uses thereof The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

Inhibitor of the mutated isocitrate dehydrogenase idh1 r132h

The present invention relates to the adduct (2E)-but-2-enedioic acid - 3-(2-{[4- (trifluoromethoxy)phenyl]amino}-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]-1H-benzimidazol- -yl)propanoic acid (1:4), methods for preparing this adduct, pharmaceutical compositions comprising this adduct and also the use of this adduct for preparing a medicament for the treatment of a disease.

Conjugates of metal complex hydroxypyridin derivatives and biomolecules and the use thereof for producing agents used in nmr diagnosis

The invention relates to conjugates of metal complex hydroxypyridin derivatives and biomolecules and to the production thereof. Said conjugates are suitable for use in the form of contrast agents in NMR diagnosis. The special embodiment of ligands makes it possible to obtain a high relaxivity and to increase a NMDR maximum.

Process for the preparation of triiodotrimesic acid

Es wird ein neues Verfahren zur Herstellung der als Zwischenprodukt für die Synthese von Rötgenkontrastmitteln verwendeten Triiodtrimesinsäure beschrieben. A novel process is described for the preparation of the triiodotrimesic acid used as an intermediate for the synthesis of red contrast agents.

Substituted triazole derivatives and uses thereof

The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

Perfluoroalkyl-containing complexes, processes for their preparation, and their use and pharmaceutical compositions containing them

Perfluoralkylhaltige Metall-Komplexe mit N-Alkylgruppe der allgemeinen Formel I wobei R entweder einen über die 1-OH- gebundenen Mono- oder Oligosaccharidrest darstellt, der optional peralkyliert ist, in diesem Falle hat Q die Bedeutung einer Gruppe ausgewählt aus δ-CO-(CH 2 ) n'' -ε δ-NH-(CH 2 ) n'' -ε δ-(CH 2 ) m -ε wobei n'' eine ganze Zahl ist von 1 und 5, und m eine ganze Zahl ist von 1 und 6, und wobei δ die Bindungsstelle zum Linker L angibt und ε die Bindungsstelle zum Rest R; oder R hat eine der folgenden Bedeutungen, dann hat Q die Bedeutung einer direkten Bindung: R bedeutet einen polaren Rest ausgewählt aus • den Komplexen K der allgemeinen Formeln II bis VIII', wobei R 1 hier ein Wasserstoffatom oder ein Metallionenäquivalent der Ordnungszahlen 20–29, 31–33, 37–39, 42–44, 49 oder 57–83 bedeutet, und die Reste R 2 , R 3 , R 4 , U, U 2 und U 1 die unten angegebene Bedeutung aufweisen, oder • eine... Perfluoroalkyl-containing metal complexes with N-alkyl group of the general formula I. in which R either represents a via the 1-OH bonded mono- or Oligosaccharidrest which is optionally peralkylated, in this case Q has the meaning of a group selected from δ-CO- (CH 2 ) n " -ε δ-NH- (CH 2 ) n " -ε δ- (CH 2 ) m -ε in which n '' is an integer of 1 and 5, and m is an integer of 1 and 6, and where δ indicates the binding site to the linker L and ε the binding site to the radical R; or R has one of the following meanings, then Q has the meaning of a direct bond: R is a polar radical selected from The complexes K of the general formulas II to VIII ', where R 1 here denotes a hydrogen atom or a metal ion equivalent of atomic numbers 20-29, 31-33, 37-39, 42-44, 49 or 57-83, and the radicals R 2 , R 3 , R 4 , U, U 2 and U 1 have the meaning given below, or • a ...

Amide-substituted aryltriazole derivatives and uses thereof

The present invention relates to novel 5-(carboxamide)-1-aryl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

A method of manufacturing a molded article and a feeder insert for use in such a method

Die Erfindung betrifft ein Verfahren zum Herstellen eines Formteils (26, 26') mit einem darin angeordneten Speisereinsatz mit einem Einguss für flüssiges Metall, für eine teilbare Gießform für den Metallguss, mit den Schritten:- Herstellen oder Bereitstellen eines mit einem geschlossenen Speisereinsatz (2, 2') ausgerüsteten Formteils (26, 26') aus einem verdichteten Formstoff (28), wobei der geschlossene Speisereinsatz (2, 2') im verdichteten Formstoff (28) des Formteils (26, 26') ortsfest angeordnet ist und eine mit Bereichen des zu bildenden Formhohlraumes (30, 30') verbundene Speiseröffnung (10, 10') aufweist, und- Öffnen des geschlossenen Speisereinsatzes (2, 2'), so dass ein Einguss (32, 32') für flüssiges Metall ausgebildet wird. The invention relates to a method for producing a molded part (26, 26 ') having a feeder insert with a sprue for liquid metal, for a divisible casting mold for metal casting, comprising the steps of: - producing or providing one with a closed feeder insert (2 , 2 ') equipped molding (26, 26') of a compressed molding material (28), wherein the closed feeder insert (2, 2 ') in the compacted molding material (28) of the molded part (26, 26') is arranged stationary and one with Having areas of the mold cavity to be formed (30, 30 ') connected to the feed opening (10, 10'), and- opening the closed feeder sleeve (2, 2 '), so that a sprue (32, 32') is formed for liquid metal.

Method for producing 5-hydroxyalkyl-substituted 1-phenyl-1,2,4-triazole derivatives

The present application relates to a novel and improved process for preparing 5-(hydroxyalkyl)-1-phenyl-1,2,4-triazole derivatives of the formula (I) in which R 1A and R 1B are independently selected from the group consisting of hydrogen, fluorine, chlorine, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, ethyl, methoxy, difluoromethoxy and trifluoromethoxy, to novel precursors for preparation thereof, and to the preparation and use of the crystalline polymorph I of (5-(4-chlorophenyl)-2-({1-(3-chlorophenyl)-5-[(1S)-1-hydroxyethyl]-1H-1,2,4-triazol-3-yl}methyl)-4-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one of the formula (I-A-1).

Conjugates of macrocyclic metal complexes with biomolecules and the utilization thereof for producing agents for use in nmr diagnosis and radiodiagnosis and radiotherapy

The invention relates to conjugates comprised of macrocyclic metal complexes with biomolecules and to the production thereof. The conjugates are suited for use as contrast agents in NMR diagnosis and radiodiagnosis and as agents for radiotherapy. A high relaxivity is achieved and a fine tuning of the relaxivity is made possible by a special liganding of the macrocycles.

Inhibitor of the mutated isocitrate dehydrogenase IDH1 R132H

The present invention relates to the adduct (2E)-but-2-enedioic acid - 3-(2-{[4- (trifluoromethoxy)phenyl]amino}-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]-1H-benzimidazol- -yl)propanoic acid (1:4), methods for preparing this adduct, pharmaceutical compositions comprising this adduct and also the use of this adduct for preparing a medicament for the treatment of a disease.

Trimeric macrocyclically substituted benzene derivatives

Operating device comprising a rotary actuator for detecting operator or user inputs

The invention relates to an operating device comprising a rotary actuator, which is accommodated in a fixed housing part (11), for detecting operator or user inputs, in particular for motor vehicles, home appliances or the like, said operating device comprising a control knob (2) which is located in a receptacle (3) and can be rotated between different selector positions about an axis of rotation (Z), wherein different functions of the rotary actuator (1) are assigned to the individual selector positions. According to the invention, at least one latching means (20) and mating latching means (21) are provided between the receptacle (3) and the housing part (11) of the operating device (10) and are located in a latched position with one another when the receptacle (3) of the control knob (2) is in an operating position (7) and, when a compressive force is exerted on the control knob (2) while the latching means (20) and/or mating latching means (21) are deflected elastically, make it possible to transfer the receptacle (3) for the control knob (2) from the operating position (7) into a retracted position and, when the compressive force on the control knob (2) is removed, cause the receptacle (3) to return from the retracted position into the operating position (7), wherein the receptacle (3) is held on the housing part (11) both in the operating position (7) and the retracted position by means of the latching means (20) and mating latching means (21).

Feeder for use in the casting of metals in casting molds

Die Erfindung betrifft einen Speisereinsatz (1, 1') zur Verwendung beim Gießen von Metallen in Gießformen, mit einem Speiserkörper (2, 2') und einem mit dem Speiserkörper (2, 2') zusammenwirkenden Speiserelement (4, 4'), welche einen Speiser-Hohlraum (6) zur Aufnahme flüssigen Metalls begrenzen, wobei - der Speiserkörper (2, 2') ein erstes Ende (8) mit einer Durchtrittsöffnung (10) für das flüssige Metall und ein dem ersten Ende (8) gegenüberliegendes zweites Ende (12) besitzt, welches offen ist, und - das Speiserelement (4, 4') an diesem zweiten, offenen Ende (12) angeordnet ist, wobei der Speiserkörper (2, 2') und das Speiserelement (4, 4') abschnittsweise teleskopartig ineinander verschiebbar sind, so dass der Speiser-Hohlraum (6) bis auf ein Mindestvolumen VK komprimierbar ist, wobei der Speiserkörper (2, 2') zumindest einen Anteil von 40 % dieses Mindestvolumens V K definiert.

Trimeric macrocyclically substituted benzene derivatives

The invention relates to the metal complexes of general formula (I), wherein Hal represents bromine or iodine, and A1 and A2 have different meanings. The inventive metal complexes are suitable for use as contrast media.

Perfluoroalkyl-containing complexes, process for their production as well as their use

Synthesis of copanlisib and its dihydrochloride salt

Prodrugs of substituted triazole derivatives and uses thereof

Macrocyclic metal complexes and use thereof for production of conjugates with biomolecules

Synthesis of copanlisib and its dihydrochloride salt

La presente invención se relaciona con un nuevo método para preparar copanlisib, diclorhidrato de copanlisib, o hidratos de diclorhidrato de copanlisib, con nuevos compuestos intermediarios, y con el uso de dichos nuevos compuestos intermediarios en la preparación de copanlisib, diclorhidrato de copanlisib, o hidratos de diclorhidrato de copanlisib. La presente invención también se relaciona con hidratos de diclorhidrato de copanlisib como compuestos.

Pharmaceutical dosage form which can be administered orally and has modified release

The invention relates to pharmaceutical dosage forms, which can be administered orally and have a modified release and contain sodium (3S)-3-(4-chloro-3-phenyl-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropylpropanoate, and to processes for preparing the dosage forms and to the use thereof for treating and/or preventing diseases, in particular for treating and/or preventing cardiac, renal, pulmonary and ophthalmological disorders, disorders of the central nervous system, fibrotic and inflammatory disorders and metabolic diseases.

Hydroxyalkyl-substituted triazole derivatives and uses thereof

The present invention relates to novel 3-(hydroxyalkyl)-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and/or cardiovascular diseases.

Pharmaceutical dosage form which can be administered orally and has modified release.

La presente invención se refiere a formas de dosificación farmacéutica de liberación modificada que pueden administrarse por vía oral que contienen ciclopropilpropanoato de sodio-(3S)-3-(4-cloro-3-{[(2S,3R)-2-(4-clorofenil)-4,4,4,4-triflu oro-3-metilbutanoil]amino}fenil)-3 así como procesos para la preparación de las formas de dosificación y su uso para el tratamiento y/o prevención de enfermedades, en particular para el tratamiento y/o la prevención de enfermedades cardíacas, renales, pulmonares y oftalmológicas, enfermedades del sistema nervioso central, enfermedades fibróticas e inflamatorias y enfermedades metabólicas.

Substituted triazole derivatives and uses thereof

The present invention relates to novel substituted 1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

Hydroxyalkyl-substituted heteroaryltriazole derivatives and uses thereof

The present invention relates to novel 5-(hydroxyalkyl)-1-heteroaryl-1,2,4-triazole derivatives, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

Synthesis of copanlisib and its dihydrochloride salt

La présente invention concerne un nouveau procédé de préparation du copanlisib, du dihydrochlorure de copanlisib ou d'hydrates de dihydrochlorure de copanlisib et de nouveaux composés intermédiaires, ainsi que l'utilisation de ces nouveaux composés intermédiaires pour la préparation dudit copanlisib, dudit dihydrochlorure de copanlisib ou desdits hydrates de dihydrochlorure de copanlisib. La présente invention concerne également des hydrates de dihydrochlorure de copanlisib en tant que composés chimiques.

Retaining device, and pin to be placed in a retaining device of said type

Die Erfindung betrifft eine Haltevorrichtung (10) mit a) einer eine Aufnahme (1) aufweisende Halterung (2), b) einem in der Aufnahme (1) der Halterung (2) längsverschiebbar geführten, federkraftbeaufschlagten und einen Stiftkopf (3) aufweisenden Stift (4), wobei der Stiftkopft (3) aus der Aufnahme (1) der Halterung (2) herausragt, c) einer Zentriereinrichtung (5), wobei die Zentriereinrichtung (5) an dem Stift (4) unverschiebbar angeordnet ist und innerhalb der Aufnahme (1) der Halterung (2) mit einer Rückstellkraft versehen ist, weiche gegen die Halterung (2) gerichtet ist.

Hydroxypyridinone derivatives, their metal complexes and their use in the production of conjugates with biomolecules

The invention relates to hydroxypyridinone derivatives, their metal complexes and their use in the production of conjugates with biomolecules. The inventive conjugates are suitable as contrast media in NMR diagnostics. A specific configuration of the ligands allows to obtain a high relaxation and to increase the NMRD maximum.

Inhibitor of the mutated isocitrate dehydrogenase IDH1 R132H

The present invention relates to the adduct (2E)-but-2-enedioic acid - 3-(2-{[4- (trifluoromethoxy)phenyl]amino}-1-[(1R,5R)-3,3,5-trimethylcyclohexyl]-1H-benzimidazol- -yl)propanoic acid (1:4), methods for preparing this adduct, pharmaceutical compositions comprising this adduct and also the use of this adduct for preparing a medicament for the treatment of a disease.

Method for producing 5-hydroxyalkyl-substituted 1-phenyl-1,2,4- triazole derivatives

The invention relates to a novel and improved method for producing 5-(hydroxyalkyl)-1-phenyl-1,2,4-triazole-derivatives of the formula (I), in which R

Prodrugs of substituted triazole derivatives and uses thereof

The present invention relates to prodrugs of 3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro- 2-hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1-[3-(trifluoromethyl)-pyridin-2-yl]- 1H-1,2,4-triazole-5-carboxamide, 3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2- hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1-[2-(trifluoromethyl)-phenyl]-1H-5 1,2,4-triazole-5-carboxamide and 3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2- hydroxypropyl]-4,5-dihydro-1H-1,2,4-triazol-1-yl}methyl)-1-(3-chloropyridin-2-yl)-1H-1,2,4- triazole-5-carboxamide, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of 10 renal and cardiovascular diseases.

INHIBITOR OF MUTATED ISOCITRATE DEHYDROGENASE IDH1 R132H

La presente invención se refiere al ácido aductivo (2E)-but-2-enedioico y ácido 3-(2-{[4-(trifluorometoxi)fenil]amino}-1-[(1R,5R)-3,3,5-trimetilciclohexil]-1H-benzimidazol-5-il)propanoico (1:4), a métodos para preparar este aducto, composiciones que comprenden este aducto y, también al uso de este aducto para preparar un medicamento para el tratamiento de una enfermedad.

Trimeric, macrocyclically substituted halo-benzene derivatives

Macrocyclic metal complexes and use thereof for production of conjugates with biomolecules

The invention relates to macrocyclic metal complexes and production and use thereof for production of conjugates with biomolecules. The conjugates are suitable as contrast agents in NMR and radio diagnostics and for radiotherapy. According to the invention, a high relaxivity and a fine-tuning of the relaxivity may be achieved by means of a special ligand formation with the macrocycles.

New metal complexes useful e.g. for manufacturing agent for X-ray diagnostics and magnetic resonance tomography-diagnostics of brain infarcts and liver tumor, and/or space-process in liver and abdomen tumors and musculoskeletal tumors

Metal complexes (A) are new. Metal complexes (A) of formula (Ia), (Ib) or (Ic) are new. Hal : Br or I; A 1>-CONR 1>-(CH 2) n-NR 2>-(CO-CHZ 1>-NH) m-CO-CHZ 2>-K 1>or -CONR 1>-(CH 2) p-(CONR 2>CH 2) m-CHOHCH 2-K 1>; A 2>A 1>or -NR 1>-CO-(NR 1>) m-(CH 2) p-NR 2>-(CO-CHZ 1>-NH) m-CO-CHZ 2>-K 1>; A 3>NR 1>-CO-R 3>or CON(R 1>) 2; V 1>direct bond, O, S, SO 2, optionally saturated 1-15C hydrocarbon chain (optionally interrupted by 1-4 O, 1-3 -NHCO-, 1-3 -CONH-, 1-2 -SO 2-, 1-2 S or 1-2 OH groups, and substituted by 1-10 OH or 1-5 1-4C alkoxy), -CONR 1>-R 3>-NR 1>CO-, -NR 1>CO-(CH 2) m-(CO) mNR 1>- or -NCOR 2>-R 3>-COR 2>N; R 1>, R 2>H, 1-2C alkyl or monohydroxy-1-2C alkyl; R 3>optionally saturated 1-15C hydrocarbon chain (optionally interrupted by 1-4 O, 1-3 -NHCO-, 1-3 -CONH-, 1-2 -SO 2-, 1-2 S or 1-2 OH groups, and substituted by 1-10 OH or 1-5 1-4C alkoxy); Z 1>, Z 2>H or CH 3; n : 0 or 2-4; m : 0 or 1; p : 1-4; K 1>macrocyclic group of formula (II); and X : H or metal ion equivalent of the atomic number 20-29, 39, 42, 44 or 57-83, with proviso that at least two X is metal ion equivalent, and optionally the free carboxyl group in (II) can exist as salts of organic and/or inorganic bases, amino acids or amino acid amides. Independent claims are included for: (1) a pharmaceutical agent comprising (A) and optionally usual galenic additives; and (2) the preparation of (A). [Image] [Image].

Prodrugs of substituted triazole derivatives and uses thereof

The present invention relates to prodrugs of 3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro- 2-hydroxypropyl] -4,5-dihydro- 1H-1,2,4-triazol-1-yl Jmethyl)-1- [3-(trifluoromethyl)-pyridin-2-yl] - 1H-1,2,4-triazole-5-carboxamide, 3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2- hydroxypropyl] -4,5-dihydro- 1H-1,2,4-triazol-1-yl} methyl)-1- [2-(trifluoromethyl)-phenyl] -1H- 1,2,4-triazole-5-carboxamide and 3-({3-(4-chlorophenyl)-5-oxo-4-[(2S)-3,3,3-trifluoro-2- hydroxypropyl] -4,5-dihydro-1H-1,2,4-triazol-1-yl} methyl)-1-(3-chloropyridin-2-yl)-1H-1,2,4- triazole-5-carboxamide, to processes for the preparation of such compounds, to pharmaceutical compositions containing such compounds, and to the use of such compounds or compositions for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of renal and cardiovascular diseases.

Perfluoralkyl containing complexes, as well as pharmaceutical composition, use and processes for the preparation thereof

COMPLEXOS CONTENDO PERFLUORALQUILA BEM COMO COMPOSIçãO FARMACêUTICA, USO E PROCESSOS DE PREPARAçãO DOS MESMOS. A presente invenção refere-se aos objetos caracterizados nas reivindicações, isto é, aos complexos de metal contendo perfluoralquila com radicais contendo nitrogênio da fórmula geral I, aos processos para sua preparação e ao seu uso no diagnóstico por RMN e por raiox X, radiodiagnóstico e radioterapia, bem como na linfografia MRT e na imagem radioisotópica de equilíbrio. COMPLEX CONTAINING PERFLUORALQUILA AS WELL AS PHARMACEUTICAL COMPOSITION, USE AND PREPARATION PROCESSES FOR THE SAME. The present invention relates to the objects characterized in the claims, i.e. perfluoralkyl-containing metal complexes containing nitrogen-containing radicals of the general formula I, processes for their preparation and their use in X-ray and NMR diagnosis, radiodiagnosis and radiotherapy, as well as MRT lymphography and balance radioisotopic imaging.

Conjugates of macrocyclic metal complexes with biomolecules and the utilization thereof for producing agents for use in NMR diagnosis and radiodiagnosis and radiotherapy

Method for producing triiodine trimesine acid

The invention relates to a novel method for producing triiodine trimesine acid used as an intermediate product for the synthesis of X-ray contrast agents.

Turntable for capturing operator or user inputs

Drehsteller (1) zur Erfassung von Bediener- oder Benutzereingaben, insbesondere für Kraftfahrzeuge, Haushaltsgeräte oder dergleichen, mit einem um eine Drehachse (Z) zwischen unterschiedlichen Wählpositionen drehbaren Bedienknopf (2), wobei den einzelnen Wählpositionen unterschiedliche Funktionen des Drehstellers (1) zugeordnet sind, wobei der Bedienknopf (2) in der Drehebene (X, Y) verschiebbar in einer Aufnahme (3) gelagert ist, dadurch gekennzeichnet, dass der Bedienknopf (2) mittels eines Kreuzschlittens (4) in der Drehebene (X, Y) des Bedienknopfes (2) verschiebbar ist, wobei der Kreuzschlitten (4) zwei in der Drehebene (X, Y) des Bedienknopfes (2) im Wesentlichen senkrecht zueinander verschiebbare Schlitten (5, 6) aufweist, wobei der Bedienknopf (2) an dem ersten Schlitten (5) gehalten ist und der zweite Schlitten (6) an einem ortsfest bezüglich der beiden Schlitten (5, 6) angeordneten Führungselement (7) im Wesentlichen senkrecht zur Verschieberichtung (X) des ersten Schlittens (5) verschiebbar entlang der Verschieberichtung (Y) geführt ist und die beiden Schlitten (5, 6) mittels wenigstens einer Rastverbindung (13) miteinander verbunden sind. Turntable (1) for recording operator or user inputs, in particular for motor vehicles, household appliances or the like, with an operating knob (2) that can be rotated about an axis of rotation (Z) between different selection positions, different functions of the turntable (1) being assigned to the individual selection positions , wherein the control knob (2) is mounted in a receptacle (3) so that it can be displaced in the plane of rotation (X, Y), characterized in that the control knob (2) can be moved in the plane of rotation (X, Y) of the control knob by means of a compound slide (4). (2) is displaceable, the compound slide (4) having two slides (5, 6) which can be displaced essentially perpendicularly to one another in the plane of rotation (X, Y) of the control knob (2), the control knob (2) being on the first ...

Chiral 3-sulfinyl benzoic acids

The invention relates to chiral 3-sulfinyl benzoic acids of the absolute configuration specified in formulae (I-R) and (I-S) as precursors for the production of herbicidal compounds. In formulae (I-R) and (I-S), X, Z and R' represent groups such as alkyl, cycloalkyl, halogen alkyl and halogen.

Shifting device

The invention relates to a shifting device for a transmission of a motor vehicle, the device comprising an actuation lever (1) which can be selectively transferred into a first selector gate, more particularly an automatic selector gate, in which said lever is mechanically coupled to a transmitting component (2) for actuating a gearshift cable or a gearshift linkage, or can be transferred into a second selector gate, more particularly a sequential selector gate, in which the lever is decoupled from the transmitting component, the transmitting component being movably mounted, more particularly pivotably mounted. A locking means (11) is provided, with which the transmitting component can be immobilized such that no force is exerted on the gearshift cable or the gearshift linkage as long as the actuation lever has been transferred into the second selector gate, and releases the transmitting component by a transfer of the actuation lever into the first selector gate.

INHIBITOR OF MUTATED ISOCITRATE DEHYDROGENASE IDH1 R132H

Se refiere a un aducto formado por el acido (2E)-but-2-enedioico y un acido 3-(2-{[4-4-trifluorometoxi)fenil]amino}-1-[(1R,5R)-3,3,5-trimetilciclohexil]-1H-benzimidazol-5-il)propanoico que comprende una molecula de acido fumarico a cuatro moleculas de acido 3-(2-{[4-4-trifluorometoxi)fenil]amino}-1-[(1R,5R)-3,3,5-trimetilciclohexil]-1H-benzimidazol-5-il)propanoico. Dicho aducto en su forma cristalina posee picos maximos en un difractograma de rayos X (2 theta) tales como 5,4; 6,8; 10,2; 10,3; 10,8; 11,1; 16,8 y 21,6. La presente invencion es util para el tratamiento y profilaxis de tumores

METAL CHELATES WITH PERFLUORATED RADICAL PEG, METHOD FOR PREPARATION AND USE

La invención se relaciona con los objetos caracterizados en las reivindicaciones, específicamente con quelatos metálicos con radical PEG perfluorado, con métodos para su preparación y con su uso para diagnóstico NMR y por rayos-X, radiodiagnóstico y radioterapia y para linfografía MRT. The invention relates to the objects characterized in the claims, specifically with metal chelates with perfluorinated PEG radical, with methods for their preparation and with their use for NMR and X-ray diagnosis, radiodiagnosis and radiotherapy and for MRT lymphography.

Macrocyclic metal complexes and use thereof for production of conjugates with biomolecules

The invention relates to macrocyclic metal complexes and production and use thereof for production of conjugates with biomolecules. The conjugates are suitable as contrast agents in NMR and radio diagnostics and for radiotherapy. According to the invention, a high relaxivity and a fine-tuning of the relaxivity may be achieved by means of a special ligand formation with the macrocycles.

Synthesis of copanlisib and its dihydrochloride salt

COPANLISIB SYNTHESIS, COPANLISIB DICLORHYDRATE, COPANLISIB DICLORHYDRATE HYDRATS AND INTERMEDIATE COMPOUNDS FOR PREPARATION

مشتقات بيريدينيل تريازول مستبدلة بأميد واستخدامها

يتعلق الاختراع الحالي بمشتقات 5-(carboxamide)-1-pyridinyl-1,2,4-triazole جديدة، وبعمليات لتحضير هذه المركبات، وبتراكيب صيدلية تحتوي على هذه المركبات، وباستخدام هذه المركبات أو التركيبات لمعالجة و/أو الوقاية من الأمراض، تحديدا لمعالجة و/أو الوقاية من الأمراض الكلوية وأمراض القلب والأوعية الدموية.

Formulación farmacéutica de polvo seco para inhalación y proceso de preparación

La presente invención se refiere a formulaciones farmacéuticas de polvo seco, que comprenden ácido (5S)-{[2-(4-carboxifenil)etil][2-(2-{[3-cloro-4’-(trifluorometil)bifenil-4-il]metoxi}fenil)etil]-amino}-5,6,7,8-tetrahidroquinolin-2-carboxílico de fórmula (1), preferiblemente en forma de una de sus sales o solvatos o hidratos, preferiblemente ácido (5S)-{[2-(4-carboxifenil)etil][2-(2-{[3-cloro-4’-(trifluorometil)bifenil-4-il]metoxi}fenil)etil]-amino}-5,6,7,8-tetrahidroquinolin-2-carboxílico monohidrato I de fórmula (1-M-I) o ácido (5S)-{[2-(4-carboxifenil)etil][2-(2-{[3-cloro-4’-(trifluorometil)bifenil-4-il]metoxi}fenil)etil]-amino}-5,6,7,8-tetrahidroquinolin-2-carboxílico monohidrato II de fórmula (1-M-II) en combinación con un portador de lactosa, que comprende lactosa monohidrato como mezcla de lactosa gruesa y lactosa fina, y al proceso de manufactura de dichas formulaciones farmacéuticas de polvo seco y su aplicación para usar en el tratamiento de trastornos cardiopulmonares, tales como hipertensión arterial pulmonar (PAH), hipertensión pulmonar tromboembólica crónica (CTEPH) e hipertensión pulmonar (PH) asociada con enfermedad pulmonar crónica (PH grupo 3) tal como hipertensión pulmonar en la enfermedad pulmonar obstructiva crónica (PH-EPOC) e hipertensión pulmonar con neumonía intersticial idiopática (PH-IIP).

Einteiliger speiserkörper zur verwendung beim giessen von metallen

Einteiliger speiserkörper zur verwendung beim giessen von metallen

Trimeric, macrocyclically substituted aminoisophthalic acid-halo-benzene derivatives

Oral applizierbare pharmazeutische darreichungsform mit modifizierter freisetzung

Procedimiento para la preparación del ácido (5s)-[2-(4-carboxifenil)etil][2-(2-[3-cloro-4’-(trifluorometil)bifenil-4-il]metoxifenil)etil]amino-5,6,7,8-tetrahidroquinolina-2-carboxílico y sus formas cristalinas para su uso como compuesto farmacéuticamente activo

La presente invención se refiere a un proceso nuevo y mejorado para preparar ácido (5S)-{[2-(4-carboxifenil)etil][2-(2-{[3-cloro-4’-(trifluorometil)bifenil-4-il]metoxi}fenil)etil]amino}-5,6,7,8-tetrahidroquinolin-2-carboxílico de fórmula (1) y a nuevas forma cristalinas de este, que es la forma pseudopolimórfica monohidrato I (1-M-I) o la forma pseudopolimórfica monohidrato II (1-M-II); además, la presente invención se refiere a un proceso de cristalización nuevo y selectivo para la preparación de la forma pseudopolimórfica monohidrato I (1-M-I) o la forma pseudopolimórfica monohidrato II (1-M-II), preferiblemente monohidrato I de fórmula (1-M-I) y a composiciones farmacéuticas que comprenden monohidrato I de fórmula (1-M-I) y a su uso para el tratamiento y/o la prevención de enfermedades, en particular para el tratamiento y/o la prevención de enfermedades pulmonares, cardiopulmonares y cardiovasculares.