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
收藏
页码：128 / 142
页数：15
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