Synthetic lipid-like materials for brain delivery

Abstract

Disclosed are (i) compounds of formula I, or pharmaceutically acceptable salts thereof; and (ii) lipidoid nanoparticles comprising compound of formula I or pharmaceutically acceptable salts thereof, as well as their use as vehicles for drug delivery across the blood-brain barrier.

1 - 49 . (canceled) 
     
     
         50 . A compound of formula I:
   Y—W—R Lipid    (I),
   or a pharmaceutically acceptable salt thereof, wherein Y is   
       
         
           
           
               
               
           
         
         W is —NR 20 —, —O—, or —S—; and 
         R 20  is R Lipid , H, C 1-6  alkyl, C 2-6  alkenyl, or C 2-6  alkynyl; and each instance of R Lipid  independently of the structure: 
         wherein: 
       
       
         
           
           
               
               
           
         
         each instance of R 1  and R 2 is independently —H, —OH, —NHR 30 , or SH; 
         R 3  and R 4  are both —H; or R 3  and R 4  are taken together to form an oxo (═O) group; 
         Z is —CH 2 —, —O—, NR 30 —, or —S—; 
         X and Y are independently —CH 2 —, —NR 30 —, —O—, —S—, or —Sc—; 
         m is an integer selected from 1-3; 
         n is an integer selected from 1-14; 
         p is 0 or 1; 
         q is an integer selected from 1-10; 
         t is 0 or 1; and 
         R 30  is —H, C 2-6  alkenyl, or C 2-6  alkynyl. 
       
     
     
         51 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , R 3  and R 4  are taken together to form an oxo (═O) group. 
     
     
         52 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , each instance of R 1  and R 2  is independently —H or —OH. 
     
     
         53 . The compound of  claim 52 , wherein, in at least one instance of R Lipid , the R 1  and R 2  are —H. 
     
     
         54 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , Z is —CH 2 —, —O—, or —NR 30 —. 
     
     
         55 . The compound of  claim 54 , wherein, in at least one instance of R Lipid , R 1  and R 2  are —H, R 3  and R 4  are taken together to form an oxo (═O) group, and Z is O. 
     
     
         56 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , R 1  is —H, R 2  is —OH, R 3  and R 4  are —H, and Z is —CH 2 —. 
     
     
         57 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , X and Y are independently —CH 2 — or —O—. 
     
     
         58 . The compound of  claim 57 , wherein, in at least one instance of R Lipid , X and Y are both —CH 2 —. 
     
     
         59 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , m is 1 or 2. 
     
     
         60 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , n is an integer selected from 4-12. 
     
     
         61 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , p is 1. 
     
     
         62 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , q is an integer selected from 2-8. 
     
     
         63 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , t is 0. 
     
     
         64 . The compound of  claim 50 , wherein, in at least one instance of R Lipid , t is 1. 
     
     
         65 . The compound of  claim 50 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         66 . A lipidoid composition, comprising a plurality of compounds of  claim 50 . 
     
     
         67 . The lipidoid nanoparticle of  claim 66 , wherein the lipidoid nanoparticle has a particle size of 25 nm to about 1000 nm. 
     
     
         68 . The lipidoid composition of  claim 66 , further comprising a protein. 
     
     
         69 . The lipidoid composition of  claim 66 , further comprising a small molecule 
     
     
         70 . The lipidoid composition of  claim 66 , further comprising a nucleic acid. 
     
     
         71 . A pharmaceutical composition, comprising a lipidoid nanoparticle of  claim 66 ; and a pharmaceutically acceptable carrier or excipient.