Synthesis of N6-substituted adenosines

Kolyachkina, Svetlana V.; Tararov, Vitali I.; Alexeev, Cyril S.; Mikhailov, Sergey N.

doi:10.1135/css201112405

Cited by 1 publication

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the synthesis of 6-(ar)alkoxy-substituted purine nucleoside derivatives (6p, 6q), 6-chloropurine-β-D-riboside (4) was reacted with sodium (ar)alkoxide in the corresponding (ar)alkyl alcohol according to a reported procedure 40,41 (Scheme 2). The 6-benzylthio-substituted derivative (6r) was synthesized from 6-chloropurine riboside (4), first converting it into 6thiopurine-riboside 29,42 followed by reaction with benzyl chloride.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5′-Nucleotidase (CD73) Inhibitors

et al. 2015

View full text Add to dashboard Cite

ecto-5'-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor α,β-methylene-ADP (AOPCP, adenosine-5'-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N(6)-Monosubstitution was superior to symmetrical N(6),N(6)-disubstitution. The most potent inhibitors were N(6)-(4-chlorobenzyl)- (10l, PSB-12441, Ki 7.23 nM), N(6)-phenylethyl- (10h, PSB-12425, Ki 8.04 nM), and N(6)-benzyl-adenosine-5'-O-[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, Ki 9.03 nM). Replacement of the 6-NH group in 10g by O (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 nM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nucleotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.

show abstract