Aza-THIP and related analogues of THIP as GABAC antagonists

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Aza-THIP and related analogues of THIP as GABAC antagonists. / Krehan, Dorte; Frølund, Bente; Ebert, Bjarke; Nielsen, Birgitte; Krogsgaard-Larsen, Povl; Johnston, Graham A.R.; Chebib, Mary.

In: Bioorganic and Medicinal Chemistry, Vol. 11, No. 23, 17.11.2003, p. 4891-4896.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Krehan, D, Frølund, B, Ebert, B, Nielsen, B, Krogsgaard-Larsen, P, Johnston, GAR & Chebib, M 2003, 'Aza-THIP and related analogues of THIP as GABAC antagonists', Bioorganic and Medicinal Chemistry, vol. 11, no. 23, pp. 4891-4896. https://doi.org/10.1016/j.bmc.2003.09.016

APA

Krehan, D., Frølund, B., Ebert, B., Nielsen, B., Krogsgaard-Larsen, P., Johnston, G. A. R., & Chebib, M. (2003). Aza-THIP and related analogues of THIP as GABAC antagonists. Bioorganic and Medicinal Chemistry, 11(23), 4891-4896. https://doi.org/10.1016/j.bmc.2003.09.016

Vancouver

Krehan D, Frølund B, Ebert B, Nielsen B, Krogsgaard-Larsen P, Johnston GAR et al. Aza-THIP and related analogues of THIP as GABAC antagonists. Bioorganic and Medicinal Chemistry. 2003 Nov 17;11(23):4891-4896. https://doi.org/10.1016/j.bmc.2003.09.016

Author

Krehan, Dorte ; Frølund, Bente ; Ebert, Bjarke ; Nielsen, Birgitte ; Krogsgaard-Larsen, Povl ; Johnston, Graham A.R. ; Chebib, Mary. / Aza-THIP and related analogues of THIP as GABAC antagonists. In: Bioorganic and Medicinal Chemistry. 2003 ; Vol. 11, No. 23. pp. 4891-4896.

Bibtex

@article{267eb6d218aa4b2bb17b2476621cf0ed,
title = "Aza-THIP and related analogues of THIP as GABAC 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 GABAC ρ1 antagonist effect (Ki=25 μM), was determined electrophysiologically using homomeric human GABAC ρ1 receptors expressed in Xenopus oocytes. Protolytic properties (pKa 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 GABAC ρ1 receptor. Within this series of moderately potent GABAC antagonists, only 4,5,6,7- tetrahydropyrazolo[5,4-c]pyridin-3-ol (Aza-THIP) does not interact detectably with GABAA receptors, and Aza-THIP has the potential of being a useful tool for molecular and behavioural pharmacological studies.",
author = "Dorte Krehan and Bente Fr{\o}lund and Bjarke Ebert and Birgitte Nielsen and Povl Krogsgaard-Larsen and Johnston, {Graham A.R.} and Mary Chebib",
year = "2003",
month = nov,
day = "17",
doi = "10.1016/j.bmc.2003.09.016",
language = "English",
volume = "11",
pages = "4891--4896",
journal = "Bioorganic & Medicinal Chemistry",
issn = "0968-0896",
publisher = "Pergamon Press",
number = "23",

}

RIS

TY - JOUR

T1 - Aza-THIP and related analogues of THIP as GABAC antagonists

AU - Krehan, Dorte

AU - Frølund, Bente

AU - Ebert, Bjarke

AU - Nielsen, Birgitte

AU - Krogsgaard-Larsen, Povl

AU - Johnston, Graham A.R.

AU - Chebib, Mary

PY - 2003/11/17

Y1 - 2003/11/17

N2 - 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 GABAC ρ1 antagonist effect (Ki=25 μM), was determined electrophysiologically using homomeric human GABAC ρ1 receptors expressed in Xenopus oocytes. Protolytic properties (pKa 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 GABAC ρ1 receptor. Within this series of moderately potent GABAC antagonists, only 4,5,6,7- tetrahydropyrazolo[5,4-c]pyridin-3-ol (Aza-THIP) does not interact detectably with GABAA receptors, and Aza-THIP has the potential of being a useful tool for molecular and behavioural pharmacological studies.

AB - 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 GABAC ρ1 antagonist effect (Ki=25 μM), was determined electrophysiologically using homomeric human GABAC ρ1 receptors expressed in Xenopus oocytes. Protolytic properties (pKa 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 GABAC ρ1 receptor. Within this series of moderately potent GABAC antagonists, only 4,5,6,7- tetrahydropyrazolo[5,4-c]pyridin-3-ol (Aza-THIP) does not interact detectably with GABAA receptors, and Aza-THIP has the potential of being a useful tool for molecular and behavioural pharmacological studies.

UR - http://www.scopus.com/inward/record.url?scp=0242361214&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2003.09.016

DO - 10.1016/j.bmc.2003.09.016

M3 - Journal article

C2 - 14604650

AN - SCOPUS:0242361214

VL - 11

SP - 4891

EP - 4896

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 23

ER -

ID: 244649793