Pyrazole-5-carboxamides, novel inhibitors of receptor for advanced glycation end products (RAGE)

被引：57

作者：

Han, Young Taek ^{[1
]}

Kim, Kyeojin ^{[2
]}

Choi, Gyeong-In ^{[2
]}

An, Hongchan ^{[2
]}

Son, Dohyun ^{[3
]}

Kim, Hee ^{[4
]}

Ha, Hee-Jin ^{[4
]}

Son, Jun-Hyeng ^{[2
]}

Chung, Suk-Jae ^{[2
]}

Park, Hyun-Ju ^{[3
]}

Lee, Jeewoo ^{[2
]}

Suh, Young-Ger ^{[2
]}

机构：

[1] Woosuk Univ, Coll Pharm, Wonju 565701, South Korea

[2] Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea

[3] Sungkyunkwan Univ, Sch Pharm, Suwon 440746, South Korea

[4] Medifron DBT, Ansan 425839, Gyeonggi Do, South Korea

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 79卷

基金：

新加坡国家研究基金会;

关键词：

RAGE (receptor for advanced glycation end products); Alzheimer's disease; RAGE inhibitor; Pyrazole-5-carboxamide; SAR (structure activity relationship); ALZHEIMERS-DISEASE; AMYLOID-BETA; CRYSTAL-STRUCTURE; KAPPA-B; PYRAZOLES; ACTIVATION; CLEARANCE; PROGRESS; PEPTIDE; BRAIN;

D O I：

10.1016/j.ejmech.2014.03.072

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In an effort to develop novel inhibitors of receptor for advanced glycation end products (RAGE) for the treatment of Alzheimer's disease, a series of pyrazole-5-carboxamides were designed, synthesized and biologically evaluated. Analyses of the extensive structure activity relationship (SAR) led us to identify a 4-fluorophenoxy analog (40) that exhibited improved in vitro RAGE inhibitory activity and more favorable aqueous solubility than the parent 2-aminopyrimidine, 1. Surface plasmon resonance (SPR) and molecular docking study strongly supported the RAGE inhibitory activity of pyrazole-5-carboxamides. The brain A beta-lowering effect of 40 is also described. (C) 2014 Elsevier Masson SAS. All rights reserved.

引用

页码：128 / 142

页数：15

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