"Reverse" carbocyclic fleximers: synthesis of a new class of adenosine deaminase inhibitors

Nucleosides Nucleotides Nucleic Acids. 2013;32(3):137-54. doi: 10.1080/15257770.2013.771187.


A series of flexible carbocyclic pyrimidine nucleosides has been designed and synthesized. In contrast to previously reported "fleximers" from our laboratory, these analogues have the connectivity of the heterocyclic base system "reversed", where the pyrimidine ring is attached to the sugar moiety, rather than the five membered imidazole ring. As was previously seen with the ribose fleximers, their inherent flexibility should allow them to adjust to enzyme binding site mutations, as well as increase the affinity for atypical enzymes. Preliminary biological screening has revealed surprising inhibition of adenosine deaminase, despite their lack of resemblance to adenosine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine Deaminase / metabolism
  • Adenosine Deaminase Inhibitors / chemical synthesis*
  • Binding Sites / genetics
  • Pyrimidine Nucleosides / chemical synthesis*
  • Pyrimidine Nucleosides / chemistry


  • Adenosine Deaminase Inhibitors
  • Pyrimidine Nucleosides
  • Adenosine Deaminase
  • Adenosine