CC BY 4.0 · Synthesis 2015; 47(11): 1593-1610
DOI: 10.1055/s-0034-1380114
paper
Copyright with the author

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)


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.

Supporting Information

 
  • References

  • 1 Contributed equally as either first or senior author.
  • 2 Kovacs A, Vasas A, Hohmann J. Phytochemistry 2008; 69: 1084-1084
    • 3a Costa BM, Irvine MW, Fang G, Eaves RJ, Mayo-Martin MB, Skifter DA, Jane DE, Monaghan DT. JPET 2010; 337: 614-614
    • 3b Monaghan DT, Irvine MW, Costa BM, Fang G, Jane DE. Neurochem. Int. 2012; 61: 581-581
    • 3c Collingridge GL, Volianskis A, Bannister N, France G, Hanna L, Mercier M, Tidball P, Fang G, Irvine MW, Costa BM, Monaghan DT, Bortolotto ZA, Molnar E, Lodge D, Jane DE. Neuropharmacology 2013; 64: 13-13
  • 4 Mosettig E, Van de Kamp J. J. Am. Chem. Soc. 1932; 54: 3328-3328
  • 5 Schultz J, Goldberg MA, Ordas EP, Carsch G. J. Org. Chem. 1946; 11: 320-320
  • 6 Klapers A, Buchwald SL. J. Am. Chem. Soc. 2002; 124: 14844-14844
  • 7 Irvine MW, Costa BM, Dlaboga D, Culley GR, Hulse R, Scholefield CL, Atlason P, Fang G, Eaves R, Morley R, Mayo-Martin MB, Amici M, Bortolotto ZA, Donaldson L, Collingridge GL, Molar E, Monaghan DT, Jane DE. J. Med. Chem. 2012; 55: 327-327
  • 8 Ruano JL. G, Aleman J, Fajardo C, Parra A. Org. Lett. 2005; 7: 5493-5493
  • 9 Fernandez F, Gonzalez C, Gomez G, Lopez C, Medina L. Arch. Pharm. 1990; 323: 239-239