71233-27-7Relevant academic research and scientific papers
GABA agonists. Synthesis and structure-activity studies on analogues of isoguvacine and THIP
Krogsgaard-Larsen,Roldskov-Christiansen
, p. 157 - 164 (2007/10/04)
A series of analogues of the specific GABA receptor agonists isoguvacine, isonipecotic acid, and THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) have been synthesized and tested as inhibitors of the binding of 3H-GABA to GABA receptor sites on rat brain membranes in vitro. Introduction of a hydroxy group into the 3- or 4-position of isonipecotic acid results in compounds with considerably reduced receptor affinity. The 7-membered ring analogues of isoguvacine and isonipecotic acid are more than two orders of magnitude weaker than the parent compounds. Replacement of the 3-isoxazolol unit of THIP by related heterocyclic rings also result in dramatic loss of activity. Thus iso-THIP (4,5,6,7-tetrahydroisoxazolo[3,4-c]pyridin-3-ol) is a weak inhibitor of 3H-GABA binding, whereas the 3-pyrazolol THIP analogues are inactive.
