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

Mary Chebib; Graham A.R. Johnston; Jan P. Mattsson; Karin Rydström; Karolina Nilsson; Jian Qiu; Scott H. Stevenson; Richard B. Silverman

doi:10.1016/S0960-894X(99)00542-9

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

Mary Chebib, Graham A.R. Johnston^*, Jan P. Mattsson, Karin Rydström, Karolina Nilsson, Jian Qiu, Scott H. Stevenson, Richard B. Silverman

^*Corresponding author for this work

Robert H. Lurie Comprehensive Cancer Center

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

3- and 4-(Aminomethyl)-2,6-difluorophenols were tested for activity against the three major classes of GABA receptors. 4-(Aminomethyl)-2,6-difluorophenol was shown to be a competitive and somewhat selective antagonist at p1 GABA(C) receptors expressed in Xenopus oocytes (K(B) = 75.5 μM with a 95% Confidence Interval range of 75.2 μM to 75.8 μM). This is the first in a novel class of increased lipophilicity GABA(C) receptor antagonists with little activity at α1β2γ2 GABA(A) and GABA(B) receptors.

Original language	English (US)
Pages (from-to)	3093-3098
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	9
Issue number	21
DOIs	https://doi.org/10.1016/S0960-894X(99)00542-9
State	Published - Nov 1 1999

ASJC Scopus subject areas

Drug Discovery
Molecular Medicine
Molecular Biology
Biochemistry
Clinical Biochemistry
Pharmaceutical Science
Organic Chemistry

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

abstract = "3- and 4-(Aminomethyl)-2,6-difluorophenols were tested for activity against the three major classes of GABA receptors. 4-(Aminomethyl)-2,6-difluorophenol was shown to be a competitive and somewhat selective antagonist at p1 GABA(C) receptors expressed in Xenopus oocytes (K(B) = 75.5 μM with a 95% Confidence Interval range of 75.2 μM to 75.8 μM). This is the first in a novel class of increased lipophilicity GABA(C) receptor antagonists with little activity at α1β2γ2 GABA(A) and GABA(B) receptors.",

author = "Mary Chebib and Johnston, {Graham A.R.} and Mattsson, {Jan P.} and Karin Rydstr{\"o}m and Karolina Nilsson and Jian Qiu and Stevenson, {Scott H.} and Silverman, {Richard B.}",

note = "Funding Information: Acknowledgments: Human pl cDNA subcloned into pcDNAI.1 was kindly provided by Dr. George Uhl (National Institute for Drug Abuse, Baltimore, MD, USA). Dr Paul Whiting (Merck Sharpe and Dohme, England) kindly provided the human ctl, 132, and T'2 cDNAs subcloned in pcDMS. M.C. and G.A.R.J. are grateful to the National Health and Medical Research Council of Australia for financial support, and R.B.S. is grateful to the U.S. Public Health Service, National Institutes of Health (NS 15703) for financial support of this work.",

year = "1999",

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doi = "10.1016/S0960-894X(99)00542-9",

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T1 - Aminomethyl-2,6-difluorophenols as a novel class of increased lipophilicity GABA(C) receptor antagonists

AU - Chebib, Mary

AU - Johnston, Graham A.R.

AU - Mattsson, Jan P.

AU - Rydström, Karin

AU - Nilsson, Karolina

AU - Qiu, Jian

AU - Stevenson, Scott H.

AU - Silverman, Richard B.

N1 - Funding Information: Acknowledgments: Human pl cDNA subcloned into pcDNAI.1 was kindly provided by Dr. George Uhl (National Institute for Drug Abuse, Baltimore, MD, USA). Dr Paul Whiting (Merck Sharpe and Dohme, England) kindly provided the human ctl, 132, and T'2 cDNAs subcloned in pcDMS. M.C. and G.A.R.J. are grateful to the National Health and Medical Research Council of Australia for financial support, and R.B.S. is grateful to the U.S. Public Health Service, National Institutes of Health (NS 15703) for financial support of this work.

PY - 1999/11/1

Y1 - 1999/11/1

N2 - 3- and 4-(Aminomethyl)-2,6-difluorophenols were tested for activity against the three major classes of GABA receptors. 4-(Aminomethyl)-2,6-difluorophenol was shown to be a competitive and somewhat selective antagonist at p1 GABA(C) receptors expressed in Xenopus oocytes (K(B) = 75.5 μM with a 95% Confidence Interval range of 75.2 μM to 75.8 μM). This is the first in a novel class of increased lipophilicity GABA(C) receptor antagonists with little activity at α1β2γ2 GABA(A) and GABA(B) receptors.

AB - 3- and 4-(Aminomethyl)-2,6-difluorophenols were tested for activity against the three major classes of GABA receptors. 4-(Aminomethyl)-2,6-difluorophenol was shown to be a competitive and somewhat selective antagonist at p1 GABA(C) receptors expressed in Xenopus oocytes (K(B) = 75.5 μM with a 95% Confidence Interval range of 75.2 μM to 75.8 μM). This is the first in a novel class of increased lipophilicity GABA(C) receptor antagonists with little activity at α1β2γ2 GABA(A) and GABA(B) receptors.

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

Abstract

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