Substituted piperidines

Abstract

The invention relates to novel substituted piperidines, to processes for preparation thereof, to the use thereof for treatment and/or prophylaxis of diseases and to the use thereof for production of medicaments for treatment and/or prophylaxis of diseases, especially of cardiovascular diseases and tumour diseases.

1 - 14 . (canceled) 
     
     
         15 . A method of prophylaxis of thromboembolic disorders in humans and animals comprising administering to the human or animal an anticoagulatory amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         in which
 R 1  is trifluoromethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, difluoromethoxy, trifluoromethoxy or ethyl, 
 R 2  is 2-hydroxyeth-1-yl, 2-methoxyeth-1-yl, 2-ethoxyeth-1-yl, cyclopropyl or 1-methoxycycloprop-1-yl, 
 R 3  is a group of the formula 
 
       
       
         
           
           
               
               
           
         
         
           where 
           * is the point of attachment to the carbonyl group, or a salt thereof. 
         
       
     
     
         16 . The method of  claim 15 , wherein in the compound of formula (I),
 R 1  is trifluoromethyl, 2,2,2-trifluoroethyl, trifluoromethoxy or ethyl,   R 2  is 2-methoxyeth-1-yl, cyclopropyl or 1-methoxycycloprop-1-yl,   R 3  is a group of the formula   
       
         
           
           
               
               
           
         
         where 
         * is the point of attachment to the carbonyl group. 
       
     
     
         17 . The method of  claim 15 , wherein in the compound of formula (I),
 R 1  is trifluoromethoxy.   R 2  is 2-methoxyeth-1-yl or cyclopropyl, and   R 3  is a group of the formula   
       
         
           
           
               
               
           
         
         where 
         * is the point of attachment to the carbonyl group. 
       
     
     
         18 . The method of  claim 15 , wherein in the compound of formula (I)
 R 1  is trifluoromethoxy,
 R 2  is cyclopropyl, and 
   R 3  is a group of the formula   
       
         
           
           
               
               
           
         
         where 
         * is the point of attachment to the carbonyl group. 
       
     
     
         19 . The method of  claim 15 , wherein the phenyl substituent and the 1,2,4-oxadiazol-5-yl substituent of the compound of formula (I) bonded to the piperidine ring are in cis positions to one another. 
     
     
         20 . The method of  claim 15 , wherein the carbon atom to which the phenyl substituent is bonded in the compound of formula (I) is in an S configuration and the carbon atom to which the 1,2,4-oxadiazol-5-yl substituent is bonded is also in an S configuration. 
     
     
         21 . The method of  claim 15 , wherein the compound of formula (I) is has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 21 , wherein the compound is a cis stereoisomer. 
     
     
         23 . The method of  claim 21 , wherein the compound of formula (I) is {3-(3-Cyclopropyl-1,2,4-oxadiazol-5-yl)-5-[4-(trifluoromethoxy)phenyl]piperidin-1-yl}(1,1-dioxidothiomorpholin-4-yl)methanone [cis isomer], or a salt thereof. 
     
     
         24 . The method of  claim 15 , wherein the compound of formula (I) is administered as a pharmaceutical composition, comprising the compound of formula (I) and an inert nontoxic pharmaceutically acceptable excipient. 
     
     
         25 . The method of  claim 15 , wherein the thromboembolic disorder is selected from the group consisting of: ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (non-STEMI), stable angina pectoris, unstable angina pectoris, reocclusions and restenoses after coronary interventions such as angioplasty, stent implantations or aortocoronary bypass, peripheral arterial occlusion diseases, pulmonary embolisms, deep venous thromboses and renal vein thromboses, transitory ischaemic attacks and also thrombotic and thromboembolic stroke. 
     
     
         26 . The method of  claim 15 , wherein the condition is a cardiogenic thromboembolism selected from the group consisting of brain ischaemias, stroke and systemic thromboembolisms and ischaemias; an acute, intermittent or persistent cardiac arrhythmia 
     
     
         27 . The method of  claim 15 , wherein the condition is a thromboembolic complication connected with microangiopathic haemolytic anaemias, extracorporeal circulation. 
     
     
         28 . A method of prophylaxis of a pulmonary disorder comprising administering to a patient in need thereof a therapeutically effective, anticoagulatory, amount of a compound of formula (I): 
       
         
           
           
               
               
           
         
         in which
 R 1  is trifluoromethyl, 1,1-difluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, difluoromethoxy, trifluoromethoxy or ethyl, 
 R 2  is 2-hydroxyeth-1-yl, 2-methoxyeth-1-yl, 2-ethoxyeth-1-yl, cyclopropyl or 1-methoxycycloprop-1-yl, 
 R 3  is a group of the formula 
 
       
       
         
           
           
               
               
           
         
         where 
         * is the point of attachment to the carbonyl group, 
       
       or a salt thereof. 
     
     
         29 . The method of  claim 28 , wherein the compound of formula (I) is administered as a pharmaceutical composition, comprising the compound of formula (I) and an inert nontoxic pharmaceutically acceptable excipient. 
     
     
         30 . The method of  claim 28 , wherein the pulmonary disorder is selected from the group consisting of pulmonary fibrosis; pulmonary hypertension, including pulmonary arterial hypertension, and disorders characterized by pulmonary occlusion; and an inflammatory pulmonary disorder.