Pharmaceutical Formulations and Ligands for Use Therein; Mimetics for UEA-1

Abstract

UEA-1 Mimetics, pharmaceutical formulations comprising them, and their uses as targeting agents for therapeutic and diagnostic purposes.

1 . A pharmaceutical formulation comprising a pharmaceutical agent and a bioadhesive ligand, said bioadhesive ligand comprising a organocyclic moiety, said organocyclic moiety a polyhydroxy- or polyalkoxy-substituted moiety.  
   
   
       2 . The pharmaceutical formulation of  claim 1  wherein the bioadhesive ligand is covalently or noncovalently bound to a carrier entity comprising the pharmaceutical agent.  
   
   
       3 . The pharmaceutical formulation of  claim 2 , wherein the carrier entity is selected from the group consisting of a nanoparticle, a microparticle, and a liposome.  
   
   
       4 . The pharmaceutical formulation of  claim 1  wherein the backbone of the organocyclic moiety comprises a backbone ring that consists of 5 to 7 atoms.  
   
   
       5 . The pharmaceutical formulation of  claim 4  wherein the ring backbone of 5 to 7 atoms is unsaturated.  
   
   
       6 . The pharmaceutical formulation of  claim 4  wherein all the atoms of the ring backbone are carbon atoms.  
   
   
       7 . The pharmaceutical formulation of  claim 4  where the backbone of the organocyclic moiety is identical to that of a radical selected from the group consisting of phenyl, napthyl, cyclohexyl, benzyl, benzoyl, pyridine, and dihydrobenzopyran.  
   
   
       8 . The pharmaceutical formulation of  claim 4  wherein the organocyclic moiety is one in which two or more hydroxyl groups are substituted in a radical selected from the group consisting of phenyl, napthyl, cyclohexyl, benzyl, benzoyl, pyridine, and dihydrobenzopyran.  
   
   
       9 . The pharmaceutical formulation of  claim 8  wherein the 2 to 4 hydroxyls are substituted in each ring backbone of the selected radical.  
   
   
       10 . The pharmaceutical formulation of  claim 8  wherein the selected radical is a galloyl radical.  
   
   
       11 . The pharmaceutical formulation of  claim 1  wherein the organocyclic moiety is covalently linked to a scaffold moiety.  
   
   
       12 . The pharmaceutical formulation of  claim 11  wherein the bioadhesive ligand comprises two or more organocyclic moieties linked by a scaffold moiety.  
   
   
       13 . The pharmaceutical formulation of  claim 12  wherein the shortest ring-to-ring length along the scaffold and between the two organocyclic moieties is from 1 to 20 atoms.  
   
   
       14 . The pharmaceutical formulation of claims  11  wherein the scaffold moiety comprises a moiety selected from the group consisting of amino acids, guanidines, hydantoins, thiohydantoins, thioureas, cathechins, acylamines, dicyclicamines, tricyclicamines, and saccharides.  
   
   
       15 . The pharmaceutical formulation of  claim 13 , wherein the scaffold moiety comprises an amino acid.  
   
   
       16 . The pharmaceutical formulation of  claim 15  wherein a trihydroxyphenyl or trimethoxyphenyl moiety is linked to the amino acid.  
   
   
       17 . The pharmaceutical formulation of claims  15  wherein the amino acid is lysine.  
   
   
       18 . The pharmaceutical formulation of  claim 15  wherein the scaffold moiety comprises a peptide comprising at least 2 amino acids.  
   
   
       19 . The pharmaceutical formulation of  claim 15  wherein a galloyl moiety is linked to both of the at least 2 amino acids.  
   
   
       20 . The pharmaceutical formulation of  claim 18  wherein the at least two amino acids are both lysines.  
   
   
       21 . The pharmaceutical formulation of  claim 14  wherein the scaffold moiety selected is an acylamine.  
   
   
       22 . The pharmaceutical formulation of  claim 21  wherein the acylamine is of the structure X—NH—(C═O)—Y, where X comprises a linear backbone comprising at least two atoms selected from the group, C and N, and wherein Y comprises an organocyclic moiety.  
   
   
       23 . The pharmaceutical formulation of  claim 20  wherein the organocylic moiety is linked to the (C═O) group of the acylamine either directly or by a linker moiety backbone that does not exceed 10 atoms.  
   
   
       24 . The pharmaceutical formulation of  claim 22  wherein the R group of at least one amino acid is linked to the X moiety of the acylamine, said amino acid selected from the group consisting of D-Norleucine, L-norleucine, D-tyrosine, L-tyrosine, D-cyclohexylalanine, D-cyclohexylalanine, D-arginine, and L-arginine.  
   
   
       25 . The pharmaceutical formulation of  claim 22  wherein an organocyclic moiety is linked to the X moiety of the acyl amine, said organocyclic moiety selected from the group consisting of D-napthylmethyl, L-napthylmethyl, and L-p-chloro-benzyl.  
   
   
       26 . The pharmaceutical formulation of  claim 22  wherein the Y moiety is selected from the group consisting of 3,4,5-trihydroxyphenyl, 3,4,5-trimethoxyphenyl, 4-biphenylmethyl, and 4-ethyl-4-biphenylmethyl.  
   
   
       27 . The pharmaceutical formulation of  claim 22  wherein —(C═O)—Y is a galloyl group.  
   
   
       28 . The pharmaceutical formulation of  claim 22  wherein X comprises 2 to 10 organocylic moieties, each linked to the linear backbone either directly or by a linker moiety backbone that does not exceed 10 atoms.  
   
   
       29 . The pharmaceutical formulation of  claim 1  wherein the bioadhesive ligand comprises a compound selected from the group consisting of those compounds specified in Tables 1, 2, 3, 4, 5, 6, 7A, 7B, and 8.  
   
   
       30 . The compound selected from the group consisting of those compounds listed in Tables 1, 2, 3, 4, 5, 6, 7, 7A, 7B, and 8.  
   
   
       31 - 38 . (canceled)