Aminomethyl-2,6-difluorophenols as a novel class of increased lipophilicity GABA(C) receptor antagonists

Bioorg Med Chem Lett. 1999 Nov 1;9(21):3093-8. doi: 10.1016/s0960-894x(99)00542-9.

Abstract

3- and 4-(Aminomethyl)-2,6-difuorophenols were tested for activity against the three major classes of GABA receptors. 4-(Amninomethyl)-2,6difluorophenol was shown to be a competitive and somewhat selective antagonist at p1 GABA(C) receptors expressed in Xenopus oocytes (K(B) = 75.5 microM with a 95% Confidence Interval range of 75.2 microM to 75.8 microM). This is the first in a novel class of increased lipophilicity GABA(C) receptor antagonists with little activity at alpha1beta2gamma2 GABA(A) and GABA(B) receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism
  • GABA Antagonists / chemical synthesis*
  • GABA Antagonists / pharmacology
  • Humans
  • Molecular Structure
  • Oocytes
  • Patch-Clamp Techniques
  • Phenols / chemical synthesis*
  • Phenols / pharmacology
  • Rats
  • Receptors, GABA / drug effects*
  • Receptors, GABA / metabolism
  • Receptors, GABA-A / metabolism
  • Receptors, GABA-B / metabolism
  • Xenopus

Substances

  • GABA Antagonists
  • GABA-C receptor
  • Phenols
  • Receptors, GABA
  • Receptors, GABA-A
  • Receptors, GABA-B