Design and synthesis of a new series of 4-alkylated 3-isoxazolol GABAA antagonists

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

Standard

Design and synthesis of a new series of 4-alkylated 3-isoxazolol GABAA antagonists. / Frølund, Bente; Tagmose, Lena; Jørgensen, Anne T.; Kristiansen, Uffe; Stensbøl, Tine B.; Liljefors, Tommy; Krogsgaard-Larsen, Povl.

In: European Journal of Medicinal Chemistry, Vol. 38, No. 4, 01.04.2003, p. 447-449.

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

Harvard

Frølund, B, Tagmose, L, Jørgensen, AT, Kristiansen, U, Stensbøl, TB, Liljefors, T & Krogsgaard-Larsen, P 2003, 'Design and synthesis of a new series of 4-alkylated 3-isoxazolol GABAA antagonists', European Journal of Medicinal Chemistry, vol. 38, no. 4, pp. 447-449. https://doi.org/10.1016/S0223-5234(03)00056-4

APA

Frølund, B., Tagmose, L., Jørgensen, A. T., Kristiansen, U., Stensbøl, T. B., Liljefors, T., & Krogsgaard-Larsen, P. (2003). Design and synthesis of a new series of 4-alkylated 3-isoxazolol GABAA antagonists. European Journal of Medicinal Chemistry, 38(4), 447-449. https://doi.org/10.1016/S0223-5234(03)00056-4

Vancouver

Frølund B, Tagmose L, Jørgensen AT, Kristiansen U, Stensbøl TB, Liljefors T et al. Design and synthesis of a new series of 4-alkylated 3-isoxazolol GABAA antagonists. European Journal of Medicinal Chemistry. 2003 Apr 1;38(4):447-449. https://doi.org/10.1016/S0223-5234(03)00056-4

Author

Frølund, Bente ; Tagmose, Lena ; Jørgensen, Anne T. ; Kristiansen, Uffe ; Stensbøl, Tine B. ; Liljefors, Tommy ; Krogsgaard-Larsen, Povl. / Design and synthesis of a new series of 4-alkylated 3-isoxazolol GABAA antagonists. In: European Journal of Medicinal Chemistry. 2003 ; Vol. 38, No. 4. pp. 447-449.

Bibtex

@article{cf2bc7493549435f8e77064e2b67161f,
title = "Design and synthesis of a new series of 4-alkylated 3-isoxazolol GABAA antagonists",
abstract = "A number of analogues of the low-efficacy partial GABAA agonist 5-(4-piperidyl)-3-isoxazolol (4-PIOL), in which the 4-position of the 3-isoxazolol ring is substituted by different groups, were synthesized and tested as GABAA receptor ligands. While alkyl and benzyl substitution provided affinities and antagonist potencies comparable to those of 4-PIOL, diphenylalkyl and naphthylalkyl substitution resulted in marked increase in both affinity and potency. The 2-naphthylmethyl and the 3,3-diphenylpropyl analogues showed antagonist potencies comparable or markedly higher than that of the standard antagonist SR 95531. Molecular modeling studies exposed a large cavity in the vicinity of the 4-position of 4-PIOL, in which there seems to be additional sites for specific receptor interactions.",
keywords = "4-PIOL, Antagonists, GABA receptor, Muscimol, THIP",
author = "Bente Fr{\o}lund and Lena Tagmose and J{\o}rgensen, {Anne T.} and Uffe Kristiansen and Stensb{\o}l, {Tine B.} and Tommy Liljefors and Povl Krogsgaard-Larsen",
year = "2003",
month = apr,
day = "1",
doi = "10.1016/S0223-5234(03)00056-4",
language = "English",
volume = "38",
pages = "447--449",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson",
number = "4",

}

RIS

TY - JOUR

T1 - Design and synthesis of a new series of 4-alkylated 3-isoxazolol GABAA antagonists

AU - Frølund, Bente

AU - Tagmose, Lena

AU - Jørgensen, Anne T.

AU - Kristiansen, Uffe

AU - Stensbøl, Tine B.

AU - Liljefors, Tommy

AU - Krogsgaard-Larsen, Povl

PY - 2003/4/1

Y1 - 2003/4/1

N2 - A number of analogues of the low-efficacy partial GABAA agonist 5-(4-piperidyl)-3-isoxazolol (4-PIOL), in which the 4-position of the 3-isoxazolol ring is substituted by different groups, were synthesized and tested as GABAA receptor ligands. While alkyl and benzyl substitution provided affinities and antagonist potencies comparable to those of 4-PIOL, diphenylalkyl and naphthylalkyl substitution resulted in marked increase in both affinity and potency. The 2-naphthylmethyl and the 3,3-diphenylpropyl analogues showed antagonist potencies comparable or markedly higher than that of the standard antagonist SR 95531. Molecular modeling studies exposed a large cavity in the vicinity of the 4-position of 4-PIOL, in which there seems to be additional sites for specific receptor interactions.

AB - A number of analogues of the low-efficacy partial GABAA agonist 5-(4-piperidyl)-3-isoxazolol (4-PIOL), in which the 4-position of the 3-isoxazolol ring is substituted by different groups, were synthesized and tested as GABAA receptor ligands. While alkyl and benzyl substitution provided affinities and antagonist potencies comparable to those of 4-PIOL, diphenylalkyl and naphthylalkyl substitution resulted in marked increase in both affinity and potency. The 2-naphthylmethyl and the 3,3-diphenylpropyl analogues showed antagonist potencies comparable or markedly higher than that of the standard antagonist SR 95531. Molecular modeling studies exposed a large cavity in the vicinity of the 4-position of 4-PIOL, in which there seems to be additional sites for specific receptor interactions.

KW - 4-PIOL

KW - Antagonists

KW - GABA receptor

KW - Muscimol

KW - THIP

UR - http://www.scopus.com/inward/record.url?scp=0037717108&partnerID=8YFLogxK

U2 - 10.1016/S0223-5234(03)00056-4

DO - 10.1016/S0223-5234(03)00056-4

M3 - Journal article

C2 - 12750034

AN - SCOPUS:0037717108

VL - 38

SP - 447

EP - 449

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

IS - 4

ER -

ID: 244649911