SAR study of a subtype selective allosteric potentiator of metabotropic glutamate 2 receptor, N-(4-phenoxyphenyl) N-(3-pyridinylmethyl)ethanesulfonamide

被引：48

作者：

Barda, DA ^{[1
]}

Wang, ZQ ^{[1
]}

Britton, TC ^{[1
]}

Henry, SS ^{[1
]}

Jagdmann, GE ^{[1
]}

Coleman, DS ^{[1
]}

Johnson, MP ^{[1
]}

Andis, SL ^{[1
]}

Schoepp, DD ^{[1
]}

机构：

[1] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 12期

关键词：

glutamate; allosteric potentiators; mGlu2; receptor;

D O I：

10.1016/j.bmcl.2004.04.017

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The major excitatory neurotransmitter in the Central Nervous System is L-glutamic acid. As a result much attention has been given to the discovery of selective modulators of both the ionotropic glutamate receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs). In this study we describe a novel class of subtype selective allosteric potentiators of the mGlu2 receptor. An active compound N-(4-phenoxyphenyl)-N-(3-pyridinylmethyl)ethanesulfonamide, LY181837, was identified in the course of compound screening. The synthesis of two series of analogs examined the structural requirements of the diaryl region of this compound. This SAR study also resulted in compounds with an increase in potency of over 100-fold where the most potent compound reported has EC50 = 14 nM. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：3099 / 3102

页数：4

共 14 条

[11] Pharmacological characterization and identification of amino acids involved in the positive modulation of metabotropic glutamate receptor subtype 2
Schaffhauser, H
Rowe, BA
Morales, S
Chavez-Noriega, LE
Yin, RY
Jachec, C
Rao, SP
Bain, G
Pinkerton, AB
Vernier, JM
Bristow, LJ
Varney, MA
Daggett, LP
[J]. MOLECULAR PHARMACOLOGY, 2003, 64 (04) : 798 - 810
[12] LY354740, an mGlu2/3 receptor agonist as a novel approach to treat anxiety/stress
Schoepp, DD
Wright, RA
Levine, LR
Gaydos, B
Potter, WZ
[J]. STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS, 2003, 6 (03): : 189 - 197
[13] Pharmacological agents acting at subtypes of metabotropic glutamate receptors
Schoepp, DD
Jane, DE
Monn, JA
[J]. NEUROPHARMACOLOGY, 1999, 38 (10) : 1431 - 1476
[14] Positive allosteric modulation of native and recombinant,γ-aminobutyric acidB receptors by 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and its aldehyde analog CGP13501
Urwyler, S
Mosbacher, J
Lingenhoehl, K
Heid, J
Hofstetter, K
Froestl, W
Bettler, B
Kaupmann, K
[J]. MOLECULAR PHARMACOLOGY, 2001, 60 (05) : 963 - 971

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