Serendipitous discovery of a new class of agonists for the melanocortin 1 and 4 receptors and a new class of cyclophanes

被引：7

作者：

Conde-Frieboes, Kilian ^{[1
]}

Ankersen, Michael ^{[2
]}

Breinholt, Jens ^{[3
]}

Hansen, Birgit Sehested ^{[4
]}

Raun, Kirsten ^{[5
]}

Thogersen, Henning ^{[6
]}

Wulff, Birgitte S. ^{[7
]}

机构：

[1] Novo Nordisk, Dept Prot & Peptide Chem, DK-2760 Malov, Denmark

[2] Novo Nordisk Inc, CMR Clin Pharmacol Res, Princeton, NJ 08540 USA

[3] Novo Nordisk, Prot Struct & Biophys, DK-2760 Malov, Denmark

[4] Novo Nordisk, Clin Pharmacol, DK-2860 Soborg, Denmark

[5] Novo Nordisk, Dept Pharmacol, DK-2760 Malov, Denmark

[6] Novo Nordisk, Struct, DK-2760 Malov, Denmark

[7] Novo Nordisk, Dept GLP & Obes Biol 1, DK-2760 Malov, Denmark

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 05期

关键词：

Melanocortin receptor 4; Agonist; Cyclophane; Combinatorial chemistry; Obesity; PHANE NOMENCLATURE; ANALOGS; OBESITY; SELECTIVITY; RESPONSES; DRUG; RAT;

D O I：

10.1016/j.bmcl.2011.01.011

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

A new class of melanocortin 4 receptor (MC4r) agonists was discovered from an unexpected sidereaction in which formaldehyde caused cyclization. These cyclophanes were found to be sub micromolar agonists of the MC1 and MC4 and were less potent on the MC3 and MC5 receptor. They were shown to compete with the peptidic antagonist SHU9119 for binding to the MC4 receptor. In an acute feeding study in Sprague Dawley rats, food intake was reduced more than 50% versus vehicle after 3 h at a dose of 1 mg/kg. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1459 / 1463

页数：5

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