Development of potent and selective inhibitors of ecto-5′- nucleotidase based on an anthraquinone scaffold

Younis Baqi, Sang Yong Lee, Jamshed Iqbal, Peter Ripphausen, Anne Lehr, Anja B. Scheiff, Herbert Zimmennann, Jürgen Bajorath, Christa E. Müller

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)


ecto-5′-Nucleotidase (eN, CD73) plays a major role in controlling extracellular adenosine levels. eN inhibitors have potential as novel drugs, for example, for the treatment of cancer. In the present study, we synthesized and investigated a series of 55 anthraquinone derivatives as potential inhibitors of eN, 11 of which are novel compounds and another 11 of which had previously been described but have now been synthesized by an improved method. We identified several potent inhibitors of rat eN. The most potent compounds were l-amino-4-[4-fluoro-2-carboxyphenylamino]-9,10-dioxo-9,10-dihydroanthracene-2- sulfonate (45, PSB-0952, K1 = 260 nM) and 1-amino-4-[2- anthracenylamino]-9,10-dioxo-9,10dihydroanthracene-2-sulfonate (52, PSB-0963, 150 nM), with 52 being the most potent eN inhibitor described to date. Selected compounds were further characterized and found to exhibit a competitive mechanism of inhibition. Investigations of ecio-nucleoside triphosphate diphosphohydrolases (NTPDases) and the P2Y receptor subtypes P2Y2, P2Y4, P2Y6, and P2Y12 showed that compound 45 exhibited the highest degree of selectivity ( > 150-fold).

Original languageEnglish
Pages (from-to)2076-2086
Number of pages11
JournalJournal of Medicinal Chemistry
Issue number5
Publication statusPublished - Mar 11 2010
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery


Dive into the research topics of 'Development of potent and selective inhibitors of ecto-5′- nucleotidase based on an anthraquinone scaffold'. Together they form a unique fingerprint.

Cite this