4-Arylphthalazin-1(2H)-one derivatives as potent antagonists of the melanin concentrating hormone receptor 1 (MCH-R1)

被引：14

作者：

Lim, Chae Jo ^{[1
,2
]}

Kim, Soo Hee ^{[1
,2
]}

Lee, Byung Ho ^{[1
]}

Oh, Kwang-Seok ^{[1
]}

Yi, Kyu Yang ^{[1
,2
]}

机构：

[1] Korea Res Inst Chem Technol, Bioorgan Sci Div, Taejon 305600, South Korea

[2] Univ Sci & Technol, Dept Med & Pharmaceut Chem, Taejon 305350, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 01期

关键词：

Melanin concentrating hormone (MCH); MCH-R1; antagonists; 4-Arylphthalazin-1(2H)-one; Obesity; OBESITY; MICE;

D O I：

10.1016/j.bmcl.2011.10.111

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of 4-arylphthalazin-1(2H)-one linked to arylpiperidines were synthesized and evaluated as MCH-R1 antagonists. The results of an extensive SAR study probing the effects of substituents on the 4-arylphthalazin-1(2H)-one C-4 aryl group led to the identification of the 4-(3,4-difluorophenyl) derivative as a highly potent MCH-R1 inhibitor with an IC50 = 1 nM. However, further investigations showed that this substance has unacceptable pharmacokinetic properties including a high clearance and volume of distribution. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：427 / 430

页数：4

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