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Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides...

by Sarwat Chowdhury, Niraj Muni, Nicholas Greenwood, David Pepperberg, Robert F Standaert
Publication Type
Journal
Journal Name
Bioorganic & Medicinal Chemistry Letters
Publication Date
Page Numbers
3745 to 3748
Volume
17
Issue
13

Lithium trialkylborohydrides were found to effect rapid monodealkylation of phosphonic diesters, and this reaction was applied to the synthesis of alkylphosphonic acid 2-aminoethyl esters [H2N(CH2)2OP(OH)R, 4], a little-explored class of analogs of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Compound 4a (R = Me) proved to be a potent antagonist at human ρ1 GABAC receptors (expressed in Xenopus laevis oocytes), with an IC50 of 11.1 �M, but is inactive at α1β2γ2 GABAA receptors.