Alkenyl substituted 2,5-piperazinediones, compositions, and uses thereof

Abstract

Provided herein are compounds of Formula (I), and salts thereof, wherein each instance of R L is independently optionally substituted C 6 -C 40 alkenyl. Further provided are compositions comprising a compound of Formula (I) and an agent. Further provided are methods and kits using the compositions for delivering an agent to a subject or cell and for treating and/or preventing a range of diseases. Further provided are methods of preparing compounds of Formula (I) and precursors thereof.

1 - 51 . (canceled) 
     
     
         52 . A compound having the following structure, 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         53 . A pharmaceutical composition comprising
 the compound of  claim 52 , or a salt thereof,   a polynucleotide;   a PEGylated lipid;   a phospholipid; and   cholesterol.   
     
     
         54 . The pharmaceutical composition of  claim 53 , wherein the polynucleotide is a modified polynucleotide comprising a modification in a base moiety, sugar moiety, and/or phosphate 
       moiety of the polynucleotide. 
     
     
         55 . The pharmaceutical composition of  claim 54 , wherein the polynucleotide comprises a modified base moiety. 
     
     
         56 . The pharmaceutical composition of  claim 53 , wherein the polynucleotide is RNA. 
     
     
         57 . The pharmaceutical composition of  claim 56 , wherein the RNA is messenger RNA, single-stranded RNA, double-stranded RNA, small interfering RNA, precursor messenger RNA, small hairpin RNA, microRNA, guide RNA, transfer RNA, antisense RNA, heterogeneous nuclear RNA, coding RNA, non-coding RNA (ncRNA), long non-coding RNA, satellite RNA, viral satellite RNA, signal recognition particle RNA, small cytoplasmic RNA, small nuclear RNA, ribosomal RNA, Piwi-interacting RNA, polyinosinic acid, ribozyme, flexizyme, small nucleolar RNA, spliced leader RNA, viral RNA, or viral satellite RNA. 
     
     
         58 . The pharmaceutical composition of  claim 53 , wherein the polynucleotide is DNA. 
     
     
         59 . The pharmaceutical composition of  claim 53 , wherein the polynucleotide comprises a sequence encoding an protein or a peptide. 
     
     
         60 . The pharmaceutical composition of  claim 59 , wherein the protein or peptide is antigenic. 
     
     
         61 . The pharmaceutical composition of  claim 60 , wherein the antigenic protein or peptide is derived from a virus. 
     
     
         62 . The pharmaceutical composition of  claim 61 , wherein the virus is influenza A virus, influenza B virus, or respiratory syncytial virus. 
     
     
         63 . The pharmaceutical composition of  claim 59 , wherein the protein or peptide is an enzyme, structural protein, receptor, soluble receptor, ion channel, active protein, cytokine, interleukin, antibody, antibody fragment, antigen, coagulation factor, albumin, growth factor, hormone, or insulin. 
     
     
         64 . The pharmaceutical composition of  claim 53 , wherein the PEGylated lipid comprises a poly(ethylene) glycol chain of up to 5 kDa in length covalently attached to a lipid with alkyl chain(s) of C 6 -C 20  length. 
     
     
         65 . The pharmaceutical composition of  claim 53 , wherein the phospholipid is selected from the group consisting of 1,2-distearoyl-snglycero-3-phosphocholine (DSPC), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoylphosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoyl-phosphatidylethanolamine (POPE), dioleoyl-phosphatidylethanolamine 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (DOPE-mal), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoyl-phosphatidyl-ethanolamine (DSPE), 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1-trans PE, and 1-stearoyl-2-oleoylphosphatidylethanolamine (SOPE).