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CC BY 4.0 · Synthesis 2015; 47(11): 1593-1610
DOI: 10.1055/s-0034-1380114
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Synthesis of a Series of Novel 3,9-Disubstituted Phenanthrenes as Analogues of Known N-Methyl-d-aspartate Receptor Allosteric Modulators

Mark W. Irvine
a   School of Physiology and Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol, BS8 1TD, UK
,
Guangyu Fang
a   School of Physiology and Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol, BS8 1TD, UK
,
Richard Eaves
a   School of Physiology and Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol, BS8 1TD, UK
,
Maria B. Mayo-Martin
a   School of Physiology and Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol, BS8 1TD, UK
,
Erica S. Burnell
a   School of Physiology and Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol, BS8 1TD, UK
,
Blaise M. Costa
b   Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-6260, USA   Email: david.jane@bristol.ac.uk
,
Georgia R. Culley
a   School of Physiology and Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol, BS8 1TD, UK
,
Arturas Volianskis
a   School of Physiology and Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol, BS8 1TD, UK
,
Graham L. Collingridge
a   School of Physiology and Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol, BS8 1TD, UK
,
Daniel T. Monaghan
b   Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198-6260, USA   Email: david.jane@bristol.ac.uk
,
David E. Jane*
a   School of Physiology and Pharmacology, Medical Sciences Building, University Walk, University of Bristol, Bristol, BS8 1TD, UK
› Author Affiliations
Further Information

Publication History

Received: 14 November 2014

Accepted after revision: 22 December 2014

Publication Date:
19 March 2015 (online)

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Abstract

9-Substituted phenanthrene-3-carboxylic acids have been reported to have allosteric modulatory activity at the N-methyl-d-aspartate (NMDA) receptor. This receptor is activated by the excitatory neurotransmitter l-glutamate and has been implicated in a range of neurological disorders such as schizophrenia, epilepsy and chronic pain, and in neurodegenerative disorders such as Alzheimer’s disease. Herein, the convenient synthesis of a wide range of novel 3,9-disubstituted phenanthrene derivatives starting from a few common intermediates is described. These new phenanthrene derivatives will help to clarify the structural requirements for allosteric modulation of the NMDA receptor.

Key words

phenanthrenes - NMDA receptor - allosteric modulators - palladium coupling - Wittig reaction

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0034–1380114.
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  • References

  • 1 Contributed equally as either first or senior author.
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