Fatty amine drug conjugates

Abstract

The invention provides conjugates of fatty amines and pharmaceutical agents useful in treating cancer, viruses, psychiatric disorders. Compositions, pharmaceutical preparations, and methods of preparations of the fatty amine-pharmaceutical agent conjugates are provided.

1 . A compound of the formula: 
       
         
           
           
               
               
           
         
         wherein R is a C 8 -C 26  fatty group of a fatty amine RNH 2  and X is an anticancer agent moiety of an anticancer agent XZH, wherein R is a C 8 -C 26  fatty group of a fatty amine RNH 2 , wherein Z is O, a primary amino group, or a secondary amino group. 
       
     
     
         2 . The compound of  claim 1 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a C 12 -C 26  fatty acid occurring naturally in humans. 
     
     
         3 . The compound of  claim 1 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a C 14 -C 24  fatty acid occurring naturally in humans. 
     
     
         4 . The compound of  claim 1 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a fatty acid selected from myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosenoic acid, docosatetraenoic acid, docosapentaenoic acid, docosahexaenoic acid, and nervonic acid. 
     
     
         5 . A pharmaceutical preparation comprising a compound of the formula: 
       
         
           
           
               
               
           
         
         wherein R is a C 8 -C 26  fatty group of a fatty amine RNH 2  and X is an anticancer drug moiety of an anticancer drug XZH, wherein Z is O, a primary amino group, or a secondary amino group. 
       
     
     
         6 . The pharmaceutical preparation of  claim 5 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a fatty acid selected from myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosenoic acid, docosatetraenoic acid, docosapentaenoic acid, docosahexaenoic acid, and nervonic acid. 
     
     
         7 . The pharmaceutical preparation of  claim 5  wherein the anticancer drug is paclitaxel. 
     
     
         8 . The pharmaceutical preparation of  claim 5 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a fatty acid occurring naturally in humans. 
     
     
         9 . The pharmaceutical preparation of  claim 5 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a C 12 -C 26  fatty acid occurring naturally in humans. 
     
     
         10 . The pharmaceutical preparation of  claim 5 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a C 14 -C 24  fatty acid occurring naturally in humans. 
     
     
         11 . A method of making a compound of the formula: 
       
         
           
           
               
               
           
         
         comprising reacting an intermediate of the formula R—N═C═O with an anticancer drug of the formula XZH for a time sufficient to form the compound wherein R is a C 8 -C 26  fatty group of a fatty amine RNH 2 , X is an anticancer drug moiety of the anticancer drug of the formula XZH, and Z is O, a primary amino group, or a secondary amino group. 
       
     
     
         12 . The method of  claim 11 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a fatty acid selected from myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosenoic acid, docosatetraenoic acid, docosapentaenoic acid, docosahexaenoic acid, and nervonic acid. 
     
     
         13 . The method of  claim 11 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a fatty acid occurring naturally in humans. 
     
     
         14 . The method of  claim 11 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a C 12 -C 26  fatty acid occurring naturally in humans. 
     
     
         15 . The method of  claim 11 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a C 14 -C 24  fatty acid occurring naturally in humans. 
     
     
         16 . A method of treating a disorder comprising administering to a subject in need of such treatment a pharmaceutical composition comprising a compound of the formula: 
       
         
           
           
               
               
           
         
         and a pharmaceutically acceptable carrier wherein R is a C 8 -C 26  fatty group of a fatty amine RNH 2  and X is an anticancer drug moiety of an anticancer drug XZH, Z is a primary amino group or a secondary amino group. 
       
     
     
         17 . The method of  claim 16 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a fatty acid selected from myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, vaccenic acid, linoleic acid, linolenic acid, arachidonic acid, eicosapentaenoic acid, docosenoic acid, docosatetraenoic acid, docosapentaenoic acid, docosahexaenoic acid, and nervonic acid. 
     
     
         18 . The method of  claim 16 , wherein the anticancer drug is paclitaxel. 
     
     
         19 . The method of  claim 16 , wherein the disorder is a mammalian cell proliferation disorder. 
     
     
         20 . The method of  claim 16 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a fatty acid occurring naturally in humans. 
     
     
         21 . The method of  claim 16 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a C 12 -C 26  fatty acid occurring naturally in humans. 
     
     
         22 . The method of  claim 16 , wherein the fatty amine RNH 2  has a carbon structure that is the same as a carbon structure of a C 14 -C 24  fatty acid occurring naturally in humans.