65456-83-9Relevant academic research and scientific papers
Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70
Cheeseman, Matthew D.,Westwood, Isaac M.,Barbeau, Olivier,Rowlands, Martin,Dobson, Sarah,Jones, Alan M.,Jeganathan, Fiona,Burke, Rosemary,Kadi, Nadia,Workman, Paul,Collins, Ian,Van Montfort, Rob L. M.,Jones, Keith
, p. 4625 - 4636 (2016/06/09)
HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought little success. This study demonstrates that adenosine-derived HSP70 inhibitors potentially bind to the protein with a novel mechanism of action, the stabilization by desolvation of an intramolecular salt-bridge which induces a conformational change in the protein, leading to high affinity ligands. We also demonstrate that through the application of this mechanism, adenosine-derived HSP70 inhibitors can be optimized in a rational manner.
Identification of 8-aminoadenosine derivatives as a new class of human concentrative nucleoside transporter 2 inhibitors
Tatani, Kazuya,Hiratochi, Masahiro,Nonaka, Yoshinori,Isaji, Masayuki,Shuto, Satoshi
supporting information, p. 244 - 248 (2015/03/30)
Purine-rich foods have long been suspected as a major cause of hyperuricemia. We hypothesized that inhibition of human concentrative nucleoside transporter 2 (hCNT2) would suppress increases in serum urate levels derived from dietary purines. To test this hypothesis, the development of potent hCNT2 inhibitors was required. By modifying adenosine, an hCNT2 substrate, we successfully identified 8-aminoadenosine derivatives as a new class of hCNT2 inhibitors. Compound 12 moderately inhibited hCNT2 (IC50 = 52 ± 3.8 μM), and subsequent structure-activity relationship studies led to the discovery of compound 48 (IC50 = 0.64 ± 0.19 μM). Here we describe significant findings about structural requirements of 8-aminoadenosine derivatives for exhibiting potent hCNT2 inhibitory activity.
Anti-HCV nucleoside derivatives
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, (2008/06/13)
The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.
Synthesis and structure-activity relationships of adenosine analogs as inhibitors of trypanosomal glyceraldehyde-3-phosphate dehydrogenase. Modifications at positions 5' and 8
Aronov, Alex M.,Gelb, Michael H.
, p. 3505 - 3510 (2007/10/03)
A number of 5', N6- and C8, N6-disubstituted adenosine analogs was synthesized and tested for inhibition of trypanosomal glyceraldehyde 3- phosphate dehydrogenase. The most active compound, N6-(3-methyl-2-buteny
SYSTEMATIC SYNTHESIS OF PURINE 8,5'-IMINO AND SUBSTITUTED IMINO CYCLONUCLEOSIDES
Sasaki, Tadashi,Minamoto, Katsumaro,Fujiki, Yasumi
, p. 1017 - 1020 (2007/10/02)
A systematic synthesis of some purine 8,5'-imino and substituted imino cyclonucleosides has been introduced.Thus, 2',3'-O-isopropylidene derivatives of 8-methylaminoadenosine, 8-methylaminoinosine, 8-benzylaminoadenosine and 8-benzylaminoinosine with exce
