Abstract
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 [H(2)N(CH(2))(2)OP(OH)R, 4], a little-explored class of analogs of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Compound 4a (R=Me) proved to be a potent antagonist at human rho1 GABA(C) receptors (expressed in Xenopus laevis oocytes), with an IC(50) of 11.1 microM, but is inactive at alpha(1)beta(2)gamma(2) GABA(A) receptors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Borohydrides / chemistry*
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Chemistry, Pharmaceutical / methods*
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Dose-Response Relationship, Drug
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Drug Design
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Esters / chemistry
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Inhibitory Concentration 50
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Lithium
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Magnetic Resonance Spectroscopy
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Models, Chemical
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Neurotransmitter Agents
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Oocytes / metabolism
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Organophosphonates / chemical synthesis*
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Organophosphonates / chemistry
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Xenopus laevis
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gamma-Aminobutyric Acid / analogs & derivatives*
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gamma-Aminobutyric Acid / chemistry*
Substances
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Borohydrides
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Esters
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Neurotransmitter Agents
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Organophosphonates
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gamma-Aminobutyric Acid
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Lithium