Chowdhury Sarwat, Muni Niraj J, Greenwood Nicholas P, Pepperberg David R, Standaert Robert F
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7056, USA.
Bioorg Med Chem Lett. 2007 Jul 1;17(13):3745-8. doi: 10.1016/j.bmcl.2007.04.026. Epub 2007 Apr 10.
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.
发现三烷基硼氢化锂能使膦酸二酯快速进行单脱烷基反应，该反应被应用于合成烷基膦酸2 - 氨基乙酯[H(2)N(CH(2))(2)OP(OH)R, 4]，这是一类研究较少的抑制性神经递质γ-氨基丁酸(GABA)类似物。化合物4a（R = Me）被证明是人类rho1 GABA(C)受体（在非洲爪蟾卵母细胞中表达）的强效拮抗剂，IC(50)为11.1 microM，但对α(1)β(2)γ(2) GABA(A)受体无活性。
