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Aza-THIP and related analogues of THIP as GABA C antagonists.

Abstract：

:The potency of a series of eight compounds structurally related with 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), a potent GABA(A) partial agonist exhibiting GABA(C) rho(1) antagonist effect (K(i)=25 microM), was determined electrophysiologically using homomeric human GABA(C) rho(1) receptors expressed in Xenopus oocytes. Protolytic properties (pK(a) values for the acidic bioisosteric groups) and the presence of steric bulk in the molecules appear to be structural parameters of importance for blockade of the GABA(C) rho(1) receptor. Within this series of moderately potent GABA(C) antagonists, only 4,5,6,7-tetrahydropyrazolo[5,4-c]pyridin-3-ol (Aza-THIP) does not interact detectably with GABA(A) receptors, and Aza-THIP has the potential of being a useful tool for molecular and behavioural pharmacological studies.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Krehan D,Frølund B,Ebert B,Nielsen B,Krogsgaard-Larsen P,Johnston GA,Chebib M

doi

10.1016/j.bmc.2003.09.016

subject

Has Abstract

pub_date

2003-11-17 00:00:00

pages

4891-6

issue

23

eissn

0968-0896

issn

1464-3391

pii

S0968089603006308

journal_volume

11

pub_type

杂志文章

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