Carbamoyloximes as novel non-competitive mGlu5 receptor antagonists

被引：21

作者：

Galambos, Janos ^{[1
]}

Wagner, Gabor ^{[1
]}

Nogradi, Katalin ^{[1
]}

Bielik, Attila ^{[1
]}

Molnar, Laszlo ^{[1
]}

Bobok, Amrita ^{[1
]}

Horvath, Attila ^{[1
]}

Kiss, Bela ^{[1
]}

Kolok, Sandor ^{[1
]}

Nagy, Jozsef ^{[1
]}

Kurko, Dalma ^{[1
]}

Bakk, Monika L. ^{[1
]}

Vastag, Monika ^{[1
]}

Saghy, Katalin ^{[1
]}

Gyertyan, Istvan ^{[1
]}

Gal, Krisztina ^{[1
]}

Greiner, Istvan ^{[1
]}

Szombathelyi, Zsolt ^{[1
]}

Keseru, Gyoergy M. ^{[1
]}

Domany, Gyoergy ^{[1
]}

机构：

[1] Gedeon Richter Plc, H-1475 Budapest, Hungary

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 15期

关键词：

mGluR5 non-competitive antagonist; carbamoyloxime; METABOTROPIC GLUTAMATE RECEPTORS; ALLOSTERIC MODULATORS; BRAIN; PHARMACOLOGY; SUBTYPE-5; DISCOVERY; FENOBAM; POTENT;

D O I：

10.1016/j.bmcl.2010.06.075

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Hit-to-lead optimization of a HTS hit led to new carbamoyloxime derivatives. After identification of an advanced hit (8d) the CYP enzyme inhibitory activity of this class of compounds was successfully eliminated. Systematic exploration of different parts of the advanced hit led us to some promising lead compounds with mGluR5 affinities comparable to that of MPEP. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4371 / 4375

页数：5

共 34 条

[1] Coordinate regulation of metabotropic glutamate receptors [J].