title: Phosphonic acid analogs of GABA through reductive dealkylation of phosphonic diesters with lithium trialkylborohydrides.
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.
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607-7056, USA.
authors.forename: Sarwat
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Niraj J
authors.initials: NJ
authors.lastname: Muni
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Greenwood
authors.forename: David R
authors.initials: DR
authors.lastname: Pepperberg
authors.forename: Robert F
authors.initials: RF
authors.lastname: Standaert
mesh_terms: D000818:Animals; D001894:Borohydrides / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004952:Esters / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008094:Lithium; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D018377:Neurotransmitter Agents; D009865:Oocytes / Q000378:metabolism; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000737:chemistry*
chemical_list: D001894:Borohydrides; D004952:Esters; D018377:Neurotransmitter Agents; D063065:Organophosphonates; D005680:gamma-Aminobutyric Acid; D008094:Lithium