Synthesis and biological evaluation of oxadiazole derivatives as inhibitors of soluble guanylyl cyclase

Margarete von Wantoch Rekowski, Anastasia Pyriochou, Nektarios Papapetropoulos, Anne Stößel, Andreas Papapetropoulos, Athanassios Giannis

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Soluble guanylyl cyclase (sGC) is an ubiquitously expressed enzyme that generates the second messenger cGMP and hence, leads to a number of physiological responses including vasodilation, inhibition of platelet aggregation and neurotransmission. Whilst many activating and stimulating modulators of sGC were identified and studied in recent years, only two selective inhibitors are known: ODQ and NS 2028. Furthermore, a synthetic approach to these inhibitors has not been reported yet. Herein, we describe a novel and efficient synthesis of these inhibitors, as well as the preparation of three different classes of NS 2028 analogues. Biological evaluation of this library using rat aortic smooth muscle cells revealed four new compounds with good to moderate sGC inhibitory activity. Our experiments underline the major importance of the oxadiazole ring in ODQ and NS 2028 for the efficiency of this class of inhibitors.

Original languageEnglish (US)
Pages (from-to)1288-1296
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number3
DOIs
StatePublished - Feb 1 2010
Externally publishedYes

Fingerprint

Oxadiazoles
Guanylate Cyclase
Derivatives
Second Messenger Systems
Platelets
Platelet Aggregation
Vasodilation
Synaptic Transmission
Modulators
Libraries
Smooth Muscle Myocytes
Muscle
Rats
Agglomeration
Cells
Enzymes
NS 2028
Soluble Guanylyl Cyclase
Experiments

Keywords

  • Inhibitor
  • Oxadiazole synthesis
  • Soluble guanylyl cyclase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Synthesis and biological evaluation of oxadiazole derivatives as inhibitors of soluble guanylyl cyclase. / von Wantoch Rekowski, Margarete; Pyriochou, Anastasia; Papapetropoulos, Nektarios; Stößel, Anne; Papapetropoulos, Andreas; Giannis, Athanassios.

In: Bioorganic and Medicinal Chemistry, Vol. 18, No. 3, 01.02.2010, p. 1288-1296.

Research output: Contribution to journalArticle

von Wantoch Rekowski, Margarete ; Pyriochou, Anastasia ; Papapetropoulos, Nektarios ; Stößel, Anne ; Papapetropoulos, Andreas ; Giannis, Athanassios. / Synthesis and biological evaluation of oxadiazole derivatives as inhibitors of soluble guanylyl cyclase. In: Bioorganic and Medicinal Chemistry. 2010 ; Vol. 18, No. 3. pp. 1288-1296.
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