Synthesis of a Series of Novel 3,9-Disubstituted Phenanthrenes as Analogues of Known N-Methyl-d-aspartate Receptor Allosteric Modulators

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.