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

共 39 条

[1] Current Therapies and New Strategies for the Management of Alzheimer's Disease
Aderinwale, Olapeju G.
Ernst, Hans W.
Mousa, Shaker A.
[J]. AMERICAN JOURNAL OF ALZHEIMERS DISEASE AND OTHER DEMENTIAS, 2010, 25 (05): : 414 - 424
[2] [Anonymous], 2011, SYBYL MOL MOD SOFTW
[3] Benchware&REG, 2011, BENCHW 3D EXPL 3D CH
[4] Self-assembly of NH-pyrazoles via intermolecular N-H•••N hydrogen bonds
Bertolasi, V
Gilli, P
Ferretti, V
Gilli, G
Fernàndez-Castaño, C
[J]. ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE CRYSTAL ENGINEERING AND MATERIALS, 1999, 55 : 985 - 993
[5] A high-throughput screening method for the determination of aqueous drug solubility using laser nephelometry in microtiter plates
Bevan, CD
Lloyd, RS
[J]. ANALYTICAL CHEMISTRY, 2000, 72 (08) : 1781 - 1787
[6] Diabetes-associated sustained activation of the transcription factor nuclear factor-κB
Bierhaus, A
Schiekofer, S
Schwaninger, M
Andrassy, M
Humpert, PM
Chen, J
Hong, M
Luther, T
Henle, T
Klöting, I
Morcos, M
Hofmann, M
Tritschler, H
Weigle, B
Kasper, M
Smith, M
Perry, G
Schmidt, AM
Stern, DM
Häring, HU
Schleicher, E
Nawroth, PP
[J]. DIABETES, 2001, 50 (12) : 2792 - 2808
[7] Alzheimer's disease
Scheltens, Philip
De Strooper, Bart
Kivipelto, Miia
Holstege, Henne
Chetelat, Gael
Teunissen, Charlotte E.
Cummings, Jeffrey
van der Flier, Wiesje M.
[J]. LANCET, 2021, 397 (10284) : 1577 - 1590
[8] Fluorine in medicinal chemistry
Böhm, HJ
Banner, D
Bendels, S
Kansy, M
Kuhn, B
Müller, K
Obst-Sander, U
Stahl, M
[J]. CHEMBIOCHEM, 2004, 5 (05) : 637 - 643
[9] 1,3-Dipolar Cycloaddition of Nitrile Imines with Functionalized Acetylenes: Regiocontrolled Sc(OTf)3-Catalyzed Synthesis of 4-and 5-Substituted Pyrazoles
Bonini, Bianca Flavia
Franchini, Mauro Comes
Gentili, Denis
Locatelli, Erika
Ricci, Alfredo
[J]. SYNLETT, 2009, (14) : 2328 - 2332
[10] RAGE mediates amyloid-β peptide transport across the blood-brain barrier and accumulation in brain
Deane, R
Yan, SD
Submamaryan, RK
LaRue, B
Jovanovic, S
Hogg, E
Welch, D
Manness, L
Lin, C
Yu, J
Zhu, H
Ghiso, J
Frangione, B
Stern, A
Schmidt, AM
Armstrong, DL
Arnold, B
Liliensiek, B
Nawroth, P
Hofman, F
Kindy, M
Stern, D
Zlokovic, B
[J]. NATURE MEDICINE, 2003, 9 (07) : 907 - 913

← 1 2 3 4 →