5542-28-9

Usage

Uses

Used in Pharmaceutical Industry:
[[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate is used as a potential therapeutic agent for various diseases due to its unique chemical structure and properties.
Used in Research and Development:
In the field of research and development, [[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate can be utilized for studying the interactions between adenosyl residues and other biomolecules, as well as for investigating the role of diadenosyl tetraphosphate compounds in cellular processes.
Used in Drug Design and Synthesis:
The unique structure of [[[[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] [(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl hydrogen phosphate makes it a valuable candidate for drug design and synthesis, particularly in the development of novel therapeutic agents targeting specific biological pathways.

InChI:InChI=1/2C10H13N5O4.4H3O4P/c2*11-8-5-9(13-2-12-8)15(3-14-5)10-7(18)6(17)4(1-16)19-10;4*1-5(2,3)4/h2*2-4,6-7,10,16-18H,1H2,(H2,11,12,13);4*(H3,1,2,3,4)/t2*4-,6-,7-,10-;;;;/m11..../s1

Upstream product

• 56-65-5 ATP 
• 59618-80-3 adenosine monophosphate tri-n-butylammonium salt 
• 20816-58-4 adenosine 5'-phosphorimidazolide 
• 4691-96-7 adenosine 5'-triphosphate sodium salt 
• 35985-27-4 lysyl adenylate 
• 170638-51-4 C₁₉H₁₉ClN₆O₁₀P₂ 
• 53355-60-5 adenosine 5'-trimetaphosphate 
• 73763-39-0 tris(tributylammonio)-ADP 
• 61-19-8 5'-adenosine monophosphate 

Downstream Products

• 58-64-0 adenosine 5'-diphosphate 
• 61-19-8 5'-adenosine monophosphate 
• 56-65-5 ATP 
• 64344-01-0 diadenosine triphosphate 

Relevant academic research and scientific papers

Reactive pyrophosphoric and bisphosphonic acid derivatives and methods of their use

This invention features bis-amides of pyrophosphoric acid and bisphosphonic acids, their preparation, and their use in synthesis of P1,P4-dinucleoside tetraphosphates, tetraphosphonates, and related compounds.

Lipophilic modifications to dinucleoside polyphosphates and nucleotides that confer antagonist properties at the platelet P2Y12 receptor

Platelet P2Y12 receptors play a central role in the regulation of platelet function and inhibition of this receptor by treatment with drugs such as clopidogrel results in a reduction of atherothrombotic events. We discovered that modification of natural and synthetic dinucleoside polyphosphates and nucleotides with lipophilic substituents on the ribose and base conferred P2Y12 receptor antagonist properties to these molecules producing potent inhibitors of ADP-mediated platelet aggregation. We describe methods for the preparation of these functionalized dinucleoside polyphosphates and nucleotides and report their associated activities. By analysis of these results and by deconstruction of the necessary structural elements through selected syntheses, we prepared a series of highly functionalized nucleotides, resulting in the selection of an adenosine monophosphate derivative (62) for further clinical development.

Solid-phase synthesis of symmetrical 5′,5′-dinucleoside mono-, di-, tri-, and tetraphosphodiesters

(Chemical Equation Presented) Four classes of phosphitylating reagents were subjected to reactions with aminomethyl polystyrene resin-bound p-acetoxybenzyl alcohol to yield the corresponding polymer-bound mono-, di-, tri-, and tetraphosphitylating reagents. The solid-phase reagents were reacted with unprotected nucleosides (e.g., thymidine, adenosine, 3′-azido-3′- deoxythymidine, cytidine, or inosine) in the presence of 5-(ethylthio)-1H- tetrazole. Polymer-bound nucleosides underwent oxidation with fert-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and the acidic cleavage, respectively, to afford 5′,5′-dinucleoside mono-, di-, tri-, and tetraphosphodiesters in 59-78% yield.

NEW USES OF DINUCLEOTIDE POLYPHOSPHATE DERIVATIVES

The present invention provides the use of analogues and derivatives of dinucleoside polyphosphates with formula (I) or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for use in one or more of: the treatment of ischemia, inducing ischemic tolerance, modulating cerebral ischemia, to delay the onset of a hypoxic depolarisation stage when ischemic events are initiated; as a neurological protection agent; as a tissue protection agent; the treatment of pain; and the treatment of inflammation, wherein X, is selected from wherein X1 and X2 are independently selected from H, Cl, Br and F; each Y is independently selected from S and O; each Z is independently selected from -CX3X4-,-NH-,-O- ; wherein X3 and X4 are selected from H, CI, Br and F; B1 and B2 are independently selected from adenine, guanine, xanthine, thymine, uracil, cytosine and inosine; S1 and S2 are independently selected from ribose, open chain ribose, 2'-deoxyribose, 3'deoxyribose and arabinofuranoside. V is selected from 0, 1 , 2, 3, 4 and 5; W is selected from 0, 1 , 2, 3, 4 and 5; and V plus W is an integer from 2 to 6.

Engineering human FHIT, a diadenosine triphosphate hydrolase, into an efficient dinucleoside polyphosphate synthase

The putative human tumor suppressor gene FHIT encodes Fhit, the fragile histidine triad protein. Fhit is thought to participate in a signal transduction pathway involving dinucleoside polyphosphates. Fhit catalyzes the Mg2+-dependent hydrolysis of P1-5′-O-adenosine-P3-5′-O-adenosine triphosphate (Ap3A) to AMP and MgADP. Mutation of His96 to glycine disables Fhit as a catalyst for the hydrolysis of phosphoanhydrides such as Ap3A. However, the mutated enzyme H96G-Fhit efficiently catalyzes the synthesis of phosphoanhydride bonds in reactions of nucleoside-5′-phosphimidazolides with nucleoside di- and triphosphates. H96G-Fhit can be employed in the synthesis of a wide range of dinucleoside tri- and tetraphosphates. We here describe the use of H96G-Fhit to catalyze the synthesis of Ap3A, Ap3C, Ap3G, Ap3T, Ap3U, Cp3U, Tp3U, dAp3U, Ap4A, Ap4U, and the fluorescent Ap4etheno-C. Copyright

Characterisation of stress protein LysU. Enzymic synthesis of diadenosine 5′,5?-P1,P4-tetraphosphate (Ap4A) analogues by LysU

The stress protein LysU (lysyl tRNA synthetase) has been purified from a recombinant strain of Escherichia coli expressing the plasmid pXLys5, and kinetically characterised. Preparative syntheses of analogues of the biologically important molecule diadenosine 5′,5?-P1,P4-tetraphosphate (Ap4A) are then achieved in good yield by enzyme catalysis, using purified LysU.

A convenient method for the synthesis of ATP and Ap4A

A bifunctional phosphorylating reagent, O-8-(5-chloroquinolyl) S-phenyl phosphorothioate (1) was employed for the synthesis of adenosine 5'- triphosphate(ATP) and diadenosine 5'-tetraphosphate(Ap4A) from adenosine 5'-phosphate(AMP) on a large scale.

Facile synthesis of nucleotides containing polyphosphates by Mn(II) and Cd(II) ion-catalyzed pyrophosphate bond formation in aqueous solution

Mn2+ and Cd2+ catalyzed pyrophosphate bond formation from adenosine-5'-phosphorimidazolide and nucleotides or phosphates in neutral aqueous solution, giving nucleotides containing polyphosphates.

Facile and Selective Synthesis of Diadenosine Polyphosphates through Catalysis by Leucyl t-RNA Synthetase Coupled with ATP Regeneration

Leucyl t-RNA synthetase from a thermophilic bacterium, Bacillus stearothermophillus, effectively catalyzed the synthesis of p1,p4-di(adenosine 5'-)tetraphosphate (Ap4A), p1,p5-di(adenosine 5'-)pentaphosphate (Ap5A) and adenosine 5'-tetraphosphate (p4A).In particular, when the reaction was coupled with an ATP recycling system involving thermostable acetate kinase and adenylate kinase, Ap4A and Ap5A were produced selectively in high yields.This reaction is selective, gives high yields and does not require protection of the functional groups of nucleotides, and also it can be carried out in an aqueous solution.This method is superior to the conventional organic synthesis and provides a practical means of the synthesizing diadenosine polyphosphates (ApnA), biologically important compounds.

Species- or isozyme-specific enzyme inhibitors. IV. Design of a two-site inhibitor of adenylate kinase with isozyme selectivity

The ATP analogues 6-(n-butylamino)-, 6-(di-n-butylamino)-, and 6-(n-butylthio)-9-β-D-ribofuranosylpurine 5'-triphosphate have been synthesized and studied as inhibitors and/or substrates of the rat muscle adenylate kinase isozyme (AK M) and the rat liver isozymes AK II and III. The 6-NH(n-Bu) and 6-S(n-Bu) analogues were substrates (V(max) relative to ATP, 13-190%) of the three AK isozymes, whereas the 6-N(n-Bu)2 analogue was a weak substrate and a competitive inhibitor of AK M and AK III. The affinities of the analogues relative to ATP [K(M) (ATP)/K(M) or K(i)] were 0.03-0.075 for AK III and 0.14-0.28 for AK M, and affinities for AK M exceeded those for AK III by factors of 2.3-7.0 P1, P6-Di(adenosine-5') pentaphosphate (Ap5A) was synthesized by an improved method and was found to be a potent two-site inhibitor (K(i) = 0.28 μM), competitive toward AMP or ATP, for the three AK isozymes. 8-SEt-Ap5A also behaved as a two-site inhibitor; the 8-SEt group reduced the affinity for AK M 12-fold but increased the affinity for AK II and III 4-fold, resulting in ca. 45-fold more effective inhibition of AK II and III (K(i) = 0.07 μM) than of AK M (K(i) = 3.25 μM). The 8-SEt group of 8-SEt-ATP likewise reduced affinity for the ATP site of AK M but enhanced affinity for the ATP sites of AK II and III, resulting in at least 30-fold more effective inhibition of AK II and III. 8-SEt-AMP inhibited AK II and III noncompetitively (K(i) = 21-24 mM) with respect to AMP, indicating that the 8-(ethylthio) adenosine moiety of 8-SEt-Ap5A probably binds to the ATP sites of these isozymes. 8-SEt-Ap5A had ca. 1000-fold more affinity for AK II or III than did 8-SEt-ATP. The findings indicate that isozyme-selective inhibitory effects of a substrate derivative can be imparted to a two-site inhibitor, leading to significant enhancement of inhibitory potency.