Selective antagonists at group I metabotropic glutamate receptors: synthesis and molecular pharmacology of 4-aryl-3-isoxazolol amino acids

Hasse Kromann; Frank A Sløk; Tine B Stensbøl; Hans Bräuner-Osborne; Ulf Madsen; Povl Krogsgaard-Larsen

Selective antagonists at group I metabotropic glutamate receptors: synthesis and molecular pharmacology of 4-aryl-3-isoxazolol amino acids

Hasse Kromann, Frank A Sløk, Tine B Stensbøl, Hans Bräuner-Osborne, Ulf Madsen, Povl Krogsgaard-Larsen

9 Citations (Scopus)

Abstract

Homologation of (S)-glutamic acid (Glu, 1) and Glu analogues has previously provided ligands with activity at metabotropic Glu receptors (mGluRs). The homologue of ibotenic acid (7), 2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid (HIBO, 8), and the 4-phenyl derivative of 8, compound 9a, are both antagonists at group I mGluRs. Here we report the synthesis and molecular pharmacology of HIBO analogues 9b-h containing different 4-aryl substituents. All of these compounds possess antagonist activity at group I mGluRs but are inactive at group II and III mGluRs.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	45
Issue number	4
Pages (from-to)	988-91
ISSN	0022-2623
Publication status	Published - 14 Feb 2002

Keywords

Animals
Brain
CHO Cells
Cricetinae
Cyclic AMP
Electrophysiology
Excitatory Amino Acid Antagonists
Hydrolysis
Isoxazoles
Phosphatidylinositols
Radioligand Assay
Rats
Receptors, Metabotropic Glutamate
Structure-Activity Relationship

Cite this

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title = "Selective antagonists at group I metabotropic glutamate receptors: synthesis and molecular pharmacology of 4-aryl-3-isoxazolol amino acids",

abstract = "Homologation of (S)-glutamic acid (Glu, 1) and Glu analogues has previously provided ligands with activity at metabotropic Glu receptors (mGluRs). The homologue of ibotenic acid (7), 2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid (HIBO, 8), and the 4-phenyl derivative of 8, compound 9a, are both antagonists at group I mGluRs. Here we report the synthesis and molecular pharmacology of HIBO analogues 9b-h containing different 4-aryl substituents. All of these compounds possess antagonist activity at group I mGluRs but are inactive at group II and III mGluRs.",

keywords = "Animals, Brain, CHO Cells, Cricetinae, Cyclic AMP, Electrophysiology, Excitatory Amino Acid Antagonists, Hydrolysis, Isoxazoles, Phosphatidylinositols, Radioligand Assay, Rats, Receptors, Metabotropic Glutamate, Structure-Activity Relationship",

author = "Hasse Kromann and Sl{\o}k, {Frank A} and Stensb{\o}l, {Tine B} and Hans Br{\"a}uner-Osborne and Ulf Madsen and Povl Krogsgaard-Larsen",

year = "2002",

month = feb,

day = "14",

language = "English",

volume = "45",

pages = "988--91",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

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TY - JOUR

T1 - Selective antagonists at group I metabotropic glutamate receptors: synthesis and molecular pharmacology of 4-aryl-3-isoxazolol amino acids

AU - Kromann, Hasse

AU - Sløk, Frank A

AU - Stensbøl, Tine B

AU - Bräuner-Osborne, Hans

AU - Madsen, Ulf

AU - Krogsgaard-Larsen, Povl

PY - 2002/2/14

Y1 - 2002/2/14

N2 - Homologation of (S)-glutamic acid (Glu, 1) and Glu analogues has previously provided ligands with activity at metabotropic Glu receptors (mGluRs). The homologue of ibotenic acid (7), 2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid (HIBO, 8), and the 4-phenyl derivative of 8, compound 9a, are both antagonists at group I mGluRs. Here we report the synthesis and molecular pharmacology of HIBO analogues 9b-h containing different 4-aryl substituents. All of these compounds possess antagonist activity at group I mGluRs but are inactive at group II and III mGluRs.

AB - Homologation of (S)-glutamic acid (Glu, 1) and Glu analogues has previously provided ligands with activity at metabotropic Glu receptors (mGluRs). The homologue of ibotenic acid (7), 2-amino-3-(3-hydroxy-5-isoxazolyl)propionic acid (HIBO, 8), and the 4-phenyl derivative of 8, compound 9a, are both antagonists at group I mGluRs. Here we report the synthesis and molecular pharmacology of HIBO analogues 9b-h containing different 4-aryl substituents. All of these compounds possess antagonist activity at group I mGluRs but are inactive at group II and III mGluRs.

KW - Animals

KW - Brain

KW - CHO Cells

KW - Cricetinae

KW - Cyclic AMP

KW - Electrophysiology

KW - Excitatory Amino Acid Antagonists

KW - Hydrolysis

KW - Isoxazoles

KW - Phosphatidylinositols

KW - Radioligand Assay

KW - Rats

KW - Receptors, Metabotropic Glutamate

KW - Structure-Activity Relationship

M3 - Journal article

C2 - 11831912

SN - 0022-2623

VL - 45

SP - 988

EP - 991

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 4

ER -

Selective antagonists at group I metabotropic glutamate receptors: synthesis and molecular pharmacology of 4-aryl-3-isoxazolol amino acids

Abstract

Keywords

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