146-76-9Relevant academic research and scientific papers
Synthesis of high specific activity tritium labelled [2-3H]-adenosine-5'-triphosphates
De Jaiswal, Vendra K.,Morimoto, Hiromi,Trump, Eric L.,Williams, Philip G.,Wemmer, David E.
, p. 743 - 752 (1996)
A procedure for high level tritium labelling at the C2-H position of adenosine 5'-triphosphate ([2-3H]-ATP, 1), based on the tritiodehalogenation reaction of 2-bromoadenosine 5'-triphosphate (2) has been elaborated. This precursor was prepared in a six-step synthesis from guanosine. The tritiodehalogenation of (2) for three hours over palladium oxide in phosphate buffer yielded tritium labelled ATP with high specific activity, in good chemical yield.
Cladribine analogues via O6-(benzotriazolyl) derivatives of guanine nucleosides
Satishkumar, Sakilam,Vuram, Prasanna K.,Relangi, Siva Subrahmanyam,Gurram, Venkateshwarlu,Zhou, Hong,Kreitman, Robert J.,Montemayor, Michelle M. Martínez,Yang, Lijia,Kaliyaperumal, Muralidharan,Sharma, Somesh,Pottabathini, Narender,Lakshman, Mahesh K.
, p. 18437 - 18463 (2015)
Cladribine, 2-chloro-2'-deoxyadenosine, is a highly efficacious, clinically used nucleoside for the treatment of hairy cell leukemia. It is also being evaluated against other lymphoid malignancies and has been a molecule of interest for well over half a century. In continuation of our interest in the amide bond-activation in purine nucleosides via the use of (benzotriazol-1yl-oxy)tris(dimethylamino)phosphonium hexafluorophosphate, we have evaluated the use of O6-(benzotriazol-1-yl)-2'-deoxyguanosine as a potential precursor to cladribine and its analogues. These compounds, after appropriate deprotection, were assessed for their biological activities, and the data are presented herein. Against hairy cell leukemia (HCL), T-cell lymphoma (TCL) and chronic lymphocytic leukemia (CLL), cladribine was the most active against all. The bromo analogue of cladribine showed comparable activity to the ribose analogue of cladribine against HCL, but was more active against TCL and CLL. The bromo ribose analogue of cladribine showed activity, but was the least active among the C6-NH2-containing compounds. Substitution with alkyl groups at the exocyclic amino group appears detrimental to activity, and only the C6 piperidinyl cladribine analogue demonstrated any activity. Against adenocarcinoma MDA-MB-231 cells, cladribine and its ribose analogue were most active.
Lipid esters of nucleoside monophosphates and their use as immunosuppressive drugs
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, (2008/06/13)
The present invention is directed to new nucleoside monophosphate derivatives of lipid ester residues of general formula (I) wherein R1 represents an optionally substituted alkyl chain having 1-20 carbon atoms; R2 represents hydrogen, an optionally substituted alkyl chain having 1-20 carbon atoms; R3, R4 and R5 represent hydrogen, hydroxy, azido, amino, cyano, or halogen; X represents a valence dash, oxygen, sulfur, a sulfinyl or sulfonyl group; Y represents a valence dash, an oxygen or sulfur atom; B represents a purine and/or pyrimidine base; with the proviso that at least one of the residues R3 or R5 is hydrogen; to their tautomers and their physiologically acceptable salts of inorganic and organic acids and/or bases, as well as to processes for their preparation, and to drugs containing said compounds.
Molecular recognition of modified adenine nucleotides by the P2Y1-receptor. 1. A synthetic, biochemical, and NMR approach
Halbfinger, Efrat,Major, Dan T.,Ritzmann, Marco,Ubl, Joachim,Reiser, Georg,Boyer, Jose L.,Harden, Kendall T.,Fischer, Bilha
, p. 5325 - 5337 (2007/10/03)
The remarkably high potencies of 2-thioether-adenine nucleotides regarding the activation of the P2Y1-receptor (P2Y1-R) in turkey erythrocyte membranes represent some of the largest substitution-promoted increases in potencies over that of a natural receptor ligand. This paper describes the investigation regarding the origin of the high potency of these P2Y1-R ligands over that of ATP. For this study, an integrated approach was employed combining the synthesis of new ATP analogues, their biochemical evaluation, and their SAR analysis involving NMR experiments and theoretical calculations. These experiments and calculations were performed to elucidate the conformation and to evaluate the electronic nature of the investigated P2Y1-R ligands. ATP analogues synthesized included derivatives where C2 or C8 positions were substituted with electron-donating groups such as ethers, thioethers, or amines. The compounds were tested for their potency to induce P2Y1-R-mediated activation of phospholipase C in turkey erythrocytes and Ca2+ response in rat astrocytes. 8-Substituted ATP and AMP derivatives had little or no effect on phospholipase C or on calcium levels, whereas the corresponding 2-substituted ATP analogues potently increased the levels of inositol phosphates and [Ca2+](i). AMP analogues were ineffective except for 2-butylthio-AMP which induced a small Ca2+ response. P2Y1-R activity of these compounds was demonstrated by testing these ligands also on NG108-15 neuroblastoma x glioma hybrid cells. NMR data together with theoretical calculations imply that steric, rather than electronic, effects play a major role in ligand binding to the P2Y1-R. Hydrophobic interactions and H-bonds of the C2 substituent appear to be important determinants of a P2Y1-R ligand affinity.
Anti-dementia agents
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, (2008/06/13)
An anti-dementia agent comprising as an active ingredient an adenosine derivative is disclosed. The anti-dementia agent is useful in the therapy of various types of dementia, especially senile dementia. Examples of the adenosine derivative include L-N6 -phenylisopropyl-adenosine, 2-chloroadenosine, N6 -cyclohexyladenosine, adenosine-5'-(N-cyclopropyl)carboxamide.
