2. Academic Validation
  3. SAR of α7 nicotinic receptor agonists derived from tilorone: exploration of a novel nicotinic pharmacophore

SAR of α7 nicotinic receptor agonists derived from tilorone: exploration of a novel nicotinic pharmacophore

  • Bioorg Med Chem Lett. 2012 Feb 15;22(4):1633-8. doi: 10.1016/j.bmcl.2011.12.126.
Michael R Schrimpf 1,  Kevin B Sippy,  Clark A Briggs,  David J Anderson,  Tao Li,  Jianguo Ji,  Jennifer M Frost,  Carol S Surowy,  William H Bunnelle,  Murali Gopalakrishnan,  Michael D Meyer
Affiliations

Affiliation

  • 1 Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6117, USA. michael.schrimpf@abbott.com
PMID: 22281189 DOI: 10.1016/j.bmcl.2011.12.126
Abstract

The well-known interferon-inducer tilorone was found to possess potent affinity for the agonist site of the α7 neuronal nicotinic receptor (K(i)=56 nM). SAR investigations determined that both basic sidechains are essential for potent activity, however active monosubstituted derivatives can also be prepared if the flexible sidechains are replaced with conformationally rigidified cyclic amines. Analogs in which the fluorenone core is replaced with either dibenzothiophene-5,5-dioxide or xanthenone also retain potent activity.

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