Ammonium salts of inositol hexaphosphate, and uses thereof

Abstract

The present invention comprises compounds, compositions thereof, and methods capable of delivering inositol hexaphospahte (IHP) to the cytoplasm of mammalian cells. In certain embodiments, the present invention relates to compounds, compositions thereof, and methods that enhance the ability of mammalian red blood cells to deliver oxygen, by delivering IHP to the cytoplasm of the red blood cells.

1 . (canceled)  
   
   
       2 . (canceled)  
   
   
       3 . (canceled)  
   
   
       4 . (canceled)  
   
   
       5 . (canceled)  
   
   
       6 . A method of enhancing oxygen delivery to a tissue or organ of a mammal, comprising the step of administering to said mammal, red blood cells or whole blood previously treated with a composition represented by structure 1:  
       n C {circle over (+)}  A n{circle over (−)}   1  
     wherein 
 nC +  represents nona-cyclohexylammonium-tri-sodium, bis-dicyclohexylammonium-deca-sodium, octa-dicyclohexylammonium, hepta-1-aza-3-hydroxyl-bicyclo[2.2.2]cyclooctanium, dodeca-1-aza-3-hydroxyl-bicyclo[2.2.2]cyclooctanium, nona-piperidinium, penta-H 3 N-Phe-OMe, nona-H 3 N-Phe-OMe, hexa-1-indanylammonium, hepta-2-norbornylammonium, nona-decahydroquinolinium, hepta-H 3 N-Phe-OEt, hexa-H 3 N-Phe-OEt, octa-H 3 N-sec-Leu-Ot-Bu, dodeca-diisopropylammonium, octa-H 3 N-Pro-Ot-Bu, deca-H 3 N-Tyr-OEt, tetra-cyclohexyl-1,2-bis-ammonium, nona-cycloheptylammonium, undeca-cyclopentylammonium, or undeca-cyclohexylammonium, penta-(N,N′-dibenzyl)-ethylenediammonium, octa menthyl-1,8-diammonium, penta cyclohexyl-(1,3-bismethylammonium), penta (±)-(1,2-trans-diphenyl)-ethylenediammonium, nona N-cyclohexyl-piperidinium, bis (N 1 ,N 3 -cyclohexyl)-dipropylenetriammonium, tris tri-(N-cyclohexyl-2-amino-ethyl)-ammonium, tetra N,N′-di-(3-(N-cyclohexyl-amino)-propyl)-piperazinium, tris tri-(N-cycloheptyl-2-amino-ethyl)-ammonium, tri N,N′-di-(3-(N-cyclooctyl-amino)-propyl)-piperazinium, or bis N,N′,N″,N′″-tetrahexyl-cyclam; and  
 A n−  represents a conjugate base of inositol hexaphosphate, wherein n equals the number of cations comprised by nC + .  
 
   
   
       7 . A method of treating a mammal afflicted with anemia, coronary infarction, pulmonary disease, congestive heart failure, diabetes, myocardial infarction, stroke, peripheral vascular disease, intermittent claudication, circulatory shock, hemorrhagic shock, chronic hypoxia, altitude sickness, arteriosclerosis, respiratory alkalemia, metabolic alkalosis, sickle cell anemia, reduced lung capacity, gangrene, anaerobic infections, carbon monoxide poisoning, nitric oxide poisoning, or cyanide poisoning, comprising the step of administering to said mammal red blood cells or whole blood previously treated with a composition represented by structure 1:  
       n C {circle over (+)}  A n{circle over (−)}   1  
     wherein 
 nC +  represents nona-cyclohexylammonium-tri-sodium, bis-dicyclohexylammonium-deca-sodium, octa-dicyclohexylammonium, hepta-1-aza-3-hydroxyl-bicyclo[2.2.2]cyclooctanium, dodeca-1-aza-3-hydroxyl-bicyclo[2.2.2]cyclooctanium, nona-piperidinium, penta-H 3 N-Phe-OMe, nona-H 3 N-Phe-OMe, hexa-1-indanylammonium, hepta-2-norbornylammonium, nona-decahydroquinolinium, hepta-H 3 N-Phe-OEt, hexa-H 3 N-Phe-OEt, octa-H 3 N-sec-Leu-Ot-Bu, dodeca-diisopropylammonium, octa-H 3 N-Pro-Ot-Bu, deca-H 3 N-Tyr-OEt, tetra-cyclohexyl-1,2-bis-ammonium, nona-cycloheptylammonium, undeca-cyclopentylammonium, or undeca-cyclohexylammonium, penta-(N,N′-dibenzyl)-ethylenediammonium, octa menthyl-1,8-diammonium, penta cyclohexyl-(1,3-bismethylammonium), penta (±)-(1,2-trans-diphenyl)-ethylenediammonium, nona N-cyclohexyl-piperidinium, bis (N 1 ,N 3 -cyclohexyl)-dipropylenetriammonium, tris tri-(N-cyclohexyl-2-amino-ethyl)-ammonium, tetra N,N′-di-(3-(N-cyclohexyl-amino)-propyl)-piperazinium, tris tri-(N-cycloheptyl-2-amino-ethyl)-ammonium, tri N,N′-di-(3-(N-cyclooctyl-amino)-propyl)-piperazinium, or bis N,N′,N″,N′″-tetrahexyl-cyclam; and  
 A n−  represents a conjugate base of inositol hexaphosphate, wherein n equals the number of cations comprised by nC + .  
 
   
   
       8 . A method of improving the oxygen delivering capability of mammalian blood, comprsing the step of adding to said mammalian blood a composition represented by structure 1:  
       n C {circle over (+)}  A n{circle over (−)}   1  
     wherein 
 nC +  represents nona-cyclohexylammonium-tri-sodium, bis-dicyclohexylammonium-deca-sodium, octa-dicyclohexylammonium, hepta-1-aza-3-hydroxyl-bicyclo[2.2.2]cyclooctanium, dodeca-1-aza-3-hydroxyl-bicyclo[2.2.2]cyclooctanium, nona-piperidinium, penta-H 3 N-Phe-OMe, nona-H 3 N-Phe-OMe, hexa-1-indanylammonium, hepta-2-norbornylammonium, nona-decahydroquinolinium, hepta-H 3 N-Phe-OEt, hexa-H 3 N-Phe-OEt, octa-H 3 N-sec-Leu-Ot-Bu, dodeca-diisopropylammonium, octa-H 3 N-Pro-Ot-Bu, deca-H 3 N-Tyr-OEt, tetra-cyclohexyl-1,2-bis-ammonium, nona-cycloheptylammonium, undeca-cyclopentylammonium, or undeca-cyclohexylammonium, penta-(N,N′-dibenzyl)-ethylenediammonium, octa menthyl-1,8-diammonium, penta cyclohexyl-(1,3-bismethylammonium), penta (±)-(1,2-trans-diphenyl)-ethylenediammonium, nona N-cyclohexyl-piperidinium, bis (N 1 ,N 3 -cyclohexyl)-dipropylenetriammonium, tris tri-(N-cyclohexyl-2-amino-ethyl)-ammonium, tetra N,N′-di-(3-(N-cyclohexyl-amino)-propyl)-piperazinium, tris tri-(N-cycloheptyl-2-amino-ethyl)-ammonium, tri N,N′-di-(3-(N-cyclooctyl-amino)-propyl)-piperazinium, or bis N,N′,N″,N′″-tetrahexyl-cyclam; and  
 A n−  represents a conjugate base of inositol hexaphosphate, wherein n equals the number of cations comprised by nC + .  
 
   
   
       9 . A method of incorporating IHP into mammalian red blood cells, comprising the step of treating said mammalian red blood cells with a composition represented by structure 1:  
       n C {circle over (+)}  A n{circle over (−)}   1  
     wherein 
 nC +  represents nona-cyclohexylammonium-tri-sodium, bis-dicyclohexylammonium-deca-sodium, octa-dicyclohexylammonium, hepta-1-aza-3-hydroxyl-bicyclo[2.2.2]cyclooctanium, dodeca-1-aza-3-hydroxyl-bicyclo[2.2.2]cyclooctanium, nona-piperidinium, penta-H 3 N-Phe-OMe, nona-H 3 N-Phe-OMe, hexa-1-indanylammonium, hepta-2-norbornylammonium, nona-decahydroquinolinium, hepta-H 3 N-Phe-OEt, hexa-H 3 N-Phe-OEt, octa-H 3 N-sec-Leu-Ot-Bu, dodeca-diisopropylammonium, octa-H 3 N-Pro-Ot-Bu, deca-H 3 N-Tyr-OEt, tetra-cyclohexyl-1,2-bis-ammonium, nona-cycloheptylammonium, undeca-cyclopentylammonium, or undeca-cyclohexylammonium, penta-(N,N′-dibenzyl)-ethylenediammonium, octa menthyl-1,8-diammonium, penta cyclohexyl-(1,3-bismethylammonium), penta (±)-(1,2-trans-diphenyl)-ethylenediammonium, nona N-cyclohexyl-piperidinium, bis (N 1 ,N 3 -cyclohexyl)-dipropylenetriammonium, tris tri-(N-cyclohexyl-2-amino-ethyl)-ammonium, tetra N,N′-di-(3-(N-cyclohexyl-amino)-propyl)-piperazinium, tris tri-(N-cycloheptyl-2-amino-ethyl)-ammonium, tri N,N′-di-(3-(N-cyclooctyl-amino)-propyl)-piperazinium, or bis N,N′,N″,N′″-tetrahexyl-cyclam; and  
 A n−  represents a conjugate base of inositol hexaphosphate, wherein n equals the number of cations comprised by nC + .