101565-69-9

Basic information

• Product Name: (2R,3S,4R,5R)-2-Hydroxymethyl-5-{6-[2-(2-methoxy-phenyl)-ethylamino]-purin-9-yl}-tetrahydro-furan-3,4-diol
• Synonyms: (2R,3S,4R,5R)-2-Hydroxymethyl-5-{6-[2-(2-methoxy-phenyl)-ethylamino]-purin-9-yl}-tetrahydro-furan-3,4-diol
• CAS NO: 101565-69-9
• Molecular Weight: 401.422
• Mol File: 101565-69-9.mol
• Article Data: 2

Chemical Properties

• CAS DataBase Reference: (2R,3S,4R,5R)-2-Hydroxymethyl-5-{6-[2-(2-methoxy-phenyl)-ethylamino]-purin-9-yl}-tetrahydro-furan-3,4-diol(CAS DataBase Reference)
• NIST Chemistry Reference: (2R,3S,4R,5R)-2-Hydroxymethyl-5-{6-[2-(2-methoxy-phenyl)-ethylamino]-purin-9-yl}-tetrahydro-furan-3,4-diol(101565-69-9)
• EPA Substance Registry System: (2R,3S,4R,5R)-2-Hydroxymethyl-5-{6-[2-(2-methoxy-phenyl)-ethylamino]-purin-9-yl}-tetrahydro-furan-3,4-diol(101565-69-9)

Safety Data

• Hazardous Substances Data: 101565-69-9(Hazardous Substances Data)

Upstream product

• 2004-06-0 6-Chloropurine riboside 
• 2045-79-6 o-methoxy-2-phenylethylamine 

Relevant articles and documents

Adenosine analogues as inhibitors of Trypanosoma brucei phosphoglycerate kinase: Elucidation of a novel binding mode for a 2-Amino-N6-substituted adenosine

As part of a project aimed at structure-based design of adenosine analogues as drugs against African trypanosomiasis, N6-, 2-amino-N6-, and N2-substituted adenosine analogues were synthesized and tested to establish structure - activity relationships for inhibiting Trypanosoma brucei glycosomal phosphoglycerate kinase (PGK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and glycerol-3-phosphate dehydrogenase (GPDH). Evaluation of X-ray structures of parasite PGK, GAPDH, and GPDH complexed with their adenosyl-bearing substrates led us to generate a series of adenosine analogues which would target all three enzymes simultaneously. There was a modest preference by PGK for N6-substituted analogues bearing the 2-amino group. The best compound in this series, 2-amino-N6-[2-(p-hydroxyphenyl)ethyl]adenosine (46b), displayed a 23-fold improvement over adenosine with an IC50 of 130 μM. 2-[[2-(p-Hydroxyphenyl)ethyl]amino]adenosine (46c) was a weak inhibitor of T. brucei PGK with an IC50 of 500 μM. To explore the potential of an additive effect that having the N6 and N2 substitutions in one molecule might provide, the best ligands from the two series were incorporated into N6,N2-disubstituted adenosine analogues to yield N6-(2-phenylethyl)-2-[(2-phenylethyl)amino]adenosine (69) as a 30 μM inhibitor of T. brucei PGK which is 100-fold more potent than the adenosine template. In contrast, these series gave no compounds that inhibited parasitic GAPDH or GPDH more than 10-20% when tested at 1.0 mM. A 3.0 A? X-ray structure of a T. brucei PGK/46b complex revealed a binding mode in which the nucleoside analogue was flipped and the ribosyl moiety adopted a syn conformation as compared with the previously determined binding mode of ADP. Molecular docking experiments using QXP and SAS program suites reproduced this 'flipped and rotated' binding mode.