Novel selective human melanocortin-3 receptor ligands:: Use of the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffold

被引：28

作者：

Ballet, Steven ^{[1
]}

Mayorov, Alexander V.

Cai, Minying

Tymecka, Dagmara

Chandler, Kevin B.

Palmer, Erin S.

Van Rompaey, Karolien

Misicka, Aleksandra

Tourwe, Dirk

Hruby, Victor J.

机构：

[1] Vrije Univ Brussels, Dept Organ Chem, B-1050 Brussels, Belgium

[2] Univ Arizona, Dept Chem, Tucson, AZ 85721 USA

[3] Warsaw Univ, Fac Chem, PL-02093 Warsaw, Poland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 09期

关键词：

human melanocortin receptors; 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-ones; cyclic lactam analogues; conformational restrictions; hMC3R/hMC5R antagonists;

D O I：

10.1016/j.bmcl.2007.02.020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In search of new selective antagonists and/or agonists for the human melanocortin receptor subtypes hMC1R to hMC5R to elucidate the specific biological roles of each GPCR, we modified the structures of the superagonist MT-II (Ac-Nle-c[Asp-HiS-D-Phe-Arg-Trp-Lys]-NH2) and the hMC3R/hMC4R antagonist SHU9119 (Ac-Nle-c[Asp-HiS-D-Nal(2 ')-Arg-Trp-Lys]-NH2) by replacing the HiS-D-Phe and HiS-D-Nal(2 ') fragments in MT-II and SHU9119, respectively, with Aba-Xxx (4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one-Xxx) dipeptidomimetics (Xxx = D-Phe/pCl-D-Phe/D-Nal(2 ')). Employment of the Aba mimetic yielded novel selective high affinity hMC3R and hMC3R/hMC5R antagonists. (C) 2007 Elsevier Ltd. All rights reserved.

引用

页码：2492 / 2498

页数：7

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