Compounds for protection of cells

Abstract

This invention is related to a compound with the structural formula (I)wherein,R1, and R2 are independently selected from the group consisting of C1-C6 alkyl and is preferably methyl, ethyl, propyl or isopropyl;R3 is selected from the group consisting of CH2NHR9, C(═O)YR10, —CH2OH

1 . Compound with the structural formula (I) 
       
         
           
           
               
               
           
         
         wherein, 
         R1, and R2 are independently selected from the group consisting of C 1 -C 6  alkyl and is preferably methyl, ethyl, propyl or isopropyl; 
         R3 is selected from the group consisting of CH 2 NHR 9 , C(═O)YR 10 , —CH2OH, 
       
       
         
           
           
               
               
           
         
         where * indicates the point of attachment of R 3  to the remainder of the molecule; 
         R 4 , R 5 , R 6 , R 7 , R 8  are independently selected from the group consisting of H, —OH, alkyl, substituted alkyl, preferably hydroxyalkyl, aryl, substituted aryl, halogen, oxygen, heteroaryl, substituted heteroaryl; 
         X is selected from the group consisting of H, O, S; 
         Y is selected from the group consisting of O, NH, S; 
         R 9  is selected from the group consisting of hydrogen, alkyl, substituted alkyl, preferably hydroxyalkyl, alkenyl, aryl, heteroaryl; 
         R 10  is selected from the group consisting of alkyl, substituted alkyl, preferably hydroxyalkyl or cyanoalkyl, aryl, OH; 
         R 11  and R 12  together with the atom N to which they are attached form a saturated or unsaturated 3-8 membered ring, incorporating one or more additional, such as one, two, or three N, O, or S atoms; 
         R 13  and R 14  together with the atom N to which they are attached form a saturated or unsaturated 3-8 membered ring, optionally substituted with alkylalcohol, and in case that R 3  is CH 2 NHR 9 , C(═O)YR 10 , —CH2OH, or 
       
       
         
           
           
               
               
           
         
       
       than is R 1  and R 2  isopropyl. 
     
     
         2 . Compounds according to  claim 1 , for use as a medicament. 
     
     
         3 . Compounds for use in treatment or prophylaxis of ischemic stroke, cerebral seizure, thrombosis, embolism, hemorrhage, cardiovascular disease, arthritis, diabetes, cancer, in particular cancer related to aging, atherosclerosis, heart failure, myocardial infarctions, schizophrenia, bipolar disorder, fragile X syndrome, sickle cell disease, and chronic fatigue syndrome, chronic obstructive pulmonary disease (COPD), a neurodegenerative disease such as Alzheimer disease, Parkinson disease, Lou Gehrig's disease, Huntington's disease, hypothermia/reperfusion, hemorrhagic shock, infection diseases involved in the attack or increased breakdown of thrombocytes, such as haemorhorragic fever, in particular ebola, Marburg disease and chagas wherein the compound has the structural formula of (I) 
       
         
           
           
               
               
           
         
         wherein, 
         R1, and R2 are independently selected from the group consisting of C 1 -C 6  alkyl and is preferably methyl, ethyl, propyl or isopropyl; 
         R3 is selected from the group consisting of —CH2OH, CH 2 NHR 9 , C(═O)YR 10 , 
       
       
         
           
           
               
               
           
         
         where * indicates the point of attachment of R 3  to the remainder of the molecule; 
         R 4 , R 5 , R 6 , R 7 , R 8  are independently selected from the group consisting of H, —OH, alkyl, substituted alkyl, preferably hydroxyalkyl, aryl, substituted aryl, halogen, oxygen, heteroaryl, substituted heteroaryl; 
         X is selected from the group consisting of H, ═O, ═S; 
         Y is selected from the group consisting of O, NH, S; 
         R 9  is selected from the group consisting of hydrogen, alkyl, substituted alkyl, preferably hydroxyalkyl or substituted hydroxyalkyl, alkylbenzylfluoride, alkenyl, aryl, substituted aryl, preferably haloaryl, heteroaryl; 
         R 10  is selected from the group consisting of hydrogen, alkyl, substituted alkyl, preferably hydroxyalkyl or cyanoalkyl, haloalkyl, alkylamide, substituted alkylamide, aryl, substituted aryl, preferably nitrobenzyl, halobenzyl, alkylbenzoyl, OH, alkenyl, alkadienyl, alkylhalide, arylhalide, —CH2(C═O)O-alkyl, heteroaryl, substituted heteroaryl, —NH—CH 2 CH 2 CN; 
         R 11  or R 12 , is alkyl, substituted alkyl, preferably an alkylamine, or form together with the atom N to which they are attached a saturated or unsaturated 3-8 membered ring, optionally incorporating one or more additional, such as one, two, or three N, O, or S atoms, optionally substituted with an alkyl, alkylalcohol; 
         R 13  and R 14  together with the atom N to which they are attached form a saturated or unsaturated 3-8 membered ring, optionally incorporating one or more additional, such as one, two, or three N, O, or S atoms, optionally substituted, preferably with an alkyl, alkylalcohol. 
       
     
     
         4 . Compounds according to any one of the  claims 1 - 3 , for use in treatment or prophylaxis of ischemia/reperfusion injury. 
     
     
         5 . Compounds according to any one of the  claims 1 - 4 , for use in treatment or prophylaxis of indications involved with oxidative stress induced cell damage. 
     
     
         6 . Compounds according to any one of the  claims 1 - 4 , for preventing aggregation of platelets in the treatment or prophylaxis of arterial thrombosis, arterial fibrillation, pulmonary embolism (PE), deep vein thrombosis (DVT), or venous thromboembolism (VTE), congestive heart failure, stroke, myocardial infarction, genetic or acquired hypercoagulability, atherosclerosis, coronary artery disease, cerebrovascular disease cerebrovascular accident, peripheral artery occlusive disease (PROD). 
     
     
         7 . Medium comprising compounds according to  claim 1  and cells. 
     
     
         8 . Medium according to  claim 7 , wherein the cells are blood platelets, mammalian cultured cells or mammalian primary cells. 
     
     
         9 . Medium comprising compounds according to  claim 1  and a tissue. 
     
     
         10 . Method for protection of cells comprising adding a compound to a cell, wherein the compound has the structural formula of (I) 
       
         
           
           
               
               
           
         
         wherein, 
         R1, and R2 are independently selected from the group consisting of C 1 -C 6  alkyl and is preferably methyl, ethyl, propyl or isopropyl; 
         R3 is selected from the group consisting of —CH2OH, CH 2 NHR 9 , C(═O)YR 10 , 
       
       
         
           
           
               
               
           
         
         where * indicates the point of attachment of R 3  to the remainder of the molecule; 
         R 4 , R 5 , R 6 , R 7 , R 8  are independently selected from the group consisting of H, —OH, alkyl, substituted alkyl, preferably hydroxyalkyl, aryl, substituted aryl, halogen, oxygen, heteroaryl, substituted heteroaryl; 
         X is selected from the group consisting of H, O, S; 
         Y is selected from the group consisting of O, NH, S; 
         R 9  is selected from the group consisting of hydrogen, alkyl, substituted alkyl, preferably hydroxyalkyl or substituted hydroxyalkyl, alkylbenzylfluoride, alkenyl, aryl, substituted aryl, preferably haloaryl, heteroaryl; 
         R 10  is selected from the group consisting of hydrogen, alkyl, substituted alkyl, preferably hydroxyalkyl or cyanoalkyl, haloalkyl, alkylamide, substituted alkylamide, aryl, substituted aryl, preferably nitrobenzyl, halobenzyl, alkylbenzoyl, OH, alkenyl, alkadienyl, alkylhalide, arylhalide, —CH2(C═O)O-alkyl, heteroaryl, substituted heteroaryl, —NH—CH 2 CH 2 CN; 
         R 11  or R 12 , alkyl, substituted alkyl, preferably an alkylamine, or form together with the atom N to which they are attached a saturated or unsaturated 3-8 membered ring, optionally incorporating one or more additional, such as one, two, or three N, O, or S atoms, optionally substituted with an alkyl, alkylalcohol; 
         R 13  and R 14  together with the atom N to which they are attached form a saturated or unsaturated 3-8 membered ring, optionally incorporating one or more additional, such as one, two, or three N, O, or S atoms, optionally substituted, preferably with an alkyl, alkylalcohol. 
       
     
     
         11 . Method according to  claim 10 , wherein the protection of cells occurs during storage. 
     
     
         12 . Method according to  claim 11 , wherein the storage occurs at a temperature below 37° C., in particular at room temperature, at about 4° C., at about −20° C. or at about −80° C. 
     
     
         13 . Method according to any one of the  claims 10  to  12 , where the addition of the compound occurs prior to cooling the cells. 
     
     
         14 . Method according to  claim 8 - 11 , wherein the cells are mammalian cultured cells, mammalian primary cells or blood platelets. 
     
     
         15 . Method according to  claim 8 - 11 , wherein the cells are blood platelets and the compounds are Sul 100, 117, 118, 125, 126, 132, 136, 138, 139, 141, 142, 143, 144, 145. 
     
     
         16 . Use of compounds according to  claim 1  or  10 , for storing cells at a temperature below 37° C., in particular at about 4° C., room temperature, about −20° C. or about −80° C.