4-Aminoquinoline melanin-concentrating hormone 1-receptor (MCH1R) antagonists

被引：17
作者：
Jiang, Jinlong
Lin, Peter
Hoang, Myle
Chang, Lehua
Tan, Carina
Feighner, Scott
Palyha, Oksana C.
Hreniuk, Donna L.
Pan, Jie
Sailer, Andreas W.
Morin, Nancy R.
MacNeil, Douglas J.
Howard, Andrew D.
Van der Ploeg, Lex H. T.
Goulet, Mark T.
DeVita, Robert J.
机构：
[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA
[2] Merck Res Labs, Dept Metab Disorders, Rahway, NJ 07065 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 20期
关键词：
MCH; melanin-concentrating hormone; antagonist; obesity; depression; anxiety; quinoline;
D O I：
10.1016/j.bmcl.2006.08.008
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Structure-activity relationships of a 4-aminoquinoline MCHlR antagonist lead series were explored by synthesis of analogs with modifications at the 2-, 4-, and 6-positions of the original HTS hit. Improvements to the original screening lead included lipophilic groups at the 2-position and biphenyl, cyclohexyl phenyl, and hydrocinnamyl carboxamides at the 6-position. Modifications of the 4-amino group were not well tolerated. (c) 2006 Elsevier Ltd. All rights reserved.
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收藏
页码：5275 / 5279
页数：5
相关论文
共 23 条
[1]   Structure-activity relationships of a novel series of melanin-concentrating hormone (MCH) receptor antagonists [J].
Arienzo, R ;
Clark, DE ;
Cramp, S ;
Daly, S ;
Dyke, HJ ;
Lockey, P ;
Norman, D ;
Roach, AG ;
Stuttle, K ;
Tomlinson, M ;
Wong, M ;
Wren, SP .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (15) :4099-4102
[2]   Synthesis and biological evaluation in vitro of selective, high affinity peptide antagonists of human melanin-concentrating hormone action at human melanin-concentrating hormone receptor 1 [J].
Bednarek, MA ;
Hreniuk, DL ;
Tan, C ;
Palyha, OC ;
MacNeil, DJ ;
Van der Ploeg, LHY ;
Howard, AD ;
Feighner, SD .
BIOCHEMISTRY, 2002, 41 (20) :6383-6390
[3]   Melanin-concentrating hormone receptor 1 antagonists for the treatment of depression and anxiety [J].
Chaki, S ;
Yamaguchi, JI ;
Yamada, H ;
Kanuma, K ;
Sekiguchi, Y .
DRUG DEVELOPMENT RESEARCH, 2005, 65 (04) :278-290
[4]   Targeted disruption of the melanin-concentrating hormone receptor-1 results in hyperphagia and resistance to diet-induced obesity [J].
Chen, YY ;
Hu, CZ ;
Hsu, CK ;
Zhang, Q ;
Bi, C ;
Asnicar, M ;
Hsiung, HM ;
Fox, N ;
Slieker, LJ ;
Yang, DD ;
Heiman, ML ;
Shi, YG .
ENDOCRINOLOGY, 2002, 143 (07) :2469-2477
[5]   A virtual screening approach to finding novel and potent antagonists at the melanin-concentrating hormone 1 receptor [J].
Clark, DE ;
Higgs, C ;
Wren, SP ;
Dyke, HJ ;
Wong, M ;
Norman, D ;
Lockey, PM ;
Roach, AG .
JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (16) :3962-3971
[6]  
Devita R.J., 2003, International Patent Application, Patent No. [WO 03/045920 A1, 03045920]
[7]  
DEVITA RJ, 2003, Patent No. 03042313
[8]   Small molecule melanin-concentrating hormone receptor 1 (MCH1R) antagonists as anxiolytic and antidepressive agents [J].
Dyck, B .
DRUG DEVELOPMENT RESEARCH, 2005, 65 (04) :291-300
[9]   Recent developments in the discovery of MCH-1R antagonists for the treatment of obesity - an update [J].
Dyke, HJ ;
Ray, NC .
EXPERT OPINION ON THERAPEUTIC PATENTS, 2005, 15 (10) :1303-1313
[10]   CATALYTIC REDUCTION OF AROMATIC NITRO-COMPOUNDS WITH HYDRAZINE IN PRESENCE OF IRON(III) CHLORIDE AND ACTIVE CARBON [J].
HIRASHIMA, T ;
MANABE, O .
CHEMISTRY LETTERS, 1975, (03) :259-260
123