A highly selective agonist for the metabotropic glutamate receptor mGluR2

被引：7

作者：

Nielsen, Simon D. ^{[1
]}

Fulco, Marica ^{[1
,2
]}

Serpi, Michaela ^{[1
,2
]}

Nielsen, Birgitte ^{[1
]}

Hansen, Maria B. ^{[1
]}

Hansen, Kasper L. ^{[1
]}

Thomsen, Christian ^{[4
]}

Brodbeck, Robb ^{[4
]}

Brauner-Osborne, Hans ^{[1
]}

Pellicciari, Roberto ^{[2
]}

Norrby, Per-Ola ^{[3
]}

Greenwood, Jeremy R. ^{[3
,5
]}

Clausen, Rasmus P. ^{[1
]}

机构：

[1] Univ Copenhagen, Fac Pharmaceut Sci, Dept Med Chem, DK-2100 Copenhagen, Denmark

[2] Univ Perugia, Dipartimento Chim & Tecnol Farmaco, I-06100 Perugia, Italy

[3] Gothenburg Univ, Dept Chem, Gothenburg, Sweden

[4] Lundbeck Res USA, Paramus, NJ USA

[5] Schrodinger Inc, New York, NY 10036 USA

来源：

MEDCHEMCOMM | 2011年 / 2卷 / 11期

基金：

英国医学研究理事会;

关键词：

PHARMACOLOGICAL CHARACTERIZATION; THERAPEUTIC PROSPECTS; DIVALENT-CATIONS; ACID; STEREOCHEMISTRY; AFFINITY; BINDING; LIGANDS;

D O I：

10.1039/c1md00186h

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The three conformationally restricted cyclopropyl glutamate analogues (3, 4, 5) were synthesised and their affinity for ionotropic and activity at metabotropic glutamate receptors were probed. Compound 4 turned out to be a highly selective agonist at the metabotropic glutamate receptor mGluR2 with at least two orders of magnitude selectivity in potency compared to the very homologous mGluR3 as well as mGluR 1, 4, 5, 7. We also tried to synthesise the two epimers of 6, but the two compounds underwent fast epimerisation in H(2)O. Furthermore, two cyclopropyl arginine analogues (7, 8) were synthesised and characterised pharmacologically at GPRC6A.

引用

页码：1120 / 1124

页数：5

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