Novel 1-(2-aminopyrazin-3-yl)methyl-2-thioureas as potent inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2)

被引：17

作者：

Lin, Songnian ^{[1
]}

Lombardo, Matthew ^{[1
]}

Malkani, Sunita ^{[1
]}

Hale, Jeffrey J. ^{[1
]}

Mills, Sander G. ^{[1
]}

Chapman, Kevin ^{[1
]}

Thompson, James E. ^{[1
]}

Zhang, Wen Xiao ^{[1
]}

Wang, Ruixiu ^{[1
]}

Cubbon, Rose M. ^{[1
]}

O'Neill, Edward A. ^{[1
]}

Luell, Silvi ^{[1
]}

Carballo-Jane, Ester ^{[1
]}

Yang, Lihu ^{[1
]}

机构：

[1] Merck Res Labs, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 12期

关键词：

MAPKAP kinase 2; MK-2; TNF alpha; Inflammation; Rheumatoid arthritis; Aminopyrazine; Thiourea; RHEUMATOID-ARTHRITIS;

D O I：

10.1016/j.bmcl.2009.04.088

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel 1-(2-aminopyrazin-3-yl)methyl-2-thioureas are described as inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2). These compounds demonstrate potent in vitro activity against the enzyme with IC50 values as low as 15 nM, and suppress expression of TNF alpha in THP-1 cells and in vivo in an acute inflammation model in mice. The synthesis, structure-activity relationship (SAR), and biological evaluation of these compounds are discussed. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3238 / 3242

页数：5

共 50 条

[11] Biological functions and role of mitogen-activated protein kinase activated protein kinase 2 (MK2) in inflammatory diseases
Rakesh Kumar Singh
Abul Kalam Najmi
Sunanda Ghosh Dastidar
Pharmacological Reports, 2017, 69 : 746 - 756
[12] Biological functions and role of mitogen-activated protein kinase activated protein kinase 2 (MK2) in inflammatory diseases
Singh, Rakesh Kumar
Najmi, Abul Kalam
Dastidar, Sunanda Ghosh
PHARMACOLOGICAL REPORTS, 2017, 69 (04) : 746 - 756
[13] Inhibition of Mitogen-Activated Protein Kinase (MAPK)-Activated Protein Kinase 2 (MK2) is Protective in Pulmonary Hypertension
Shafid, Mohammad
Jagavelu, Kumaravelu
Iqbal, Hina
Yadav, Pankaj
Chanda, Debabrata
Verma, Neeraj Kumar
Ghosh, Jimut Kanti
Gaestel, Matthias
Hanif, Kashif
HYPERTENSION, 2021, 77 (04) : 1248 - 1259
[14] Mitogen-activated Protein Kinase-activated Protein Kinase 2 Inhibition Attenuates Fibroblast Invasion and Severe Lung Fibrosis
Liang, Jiurong
Liu, Ningshan
Liu, Xue
Mena, Jessica Monterrosa
Xie, Ting
Geng, Yan
Huan, Caijuan
Zhang, Yanli
Taghavifar, Forough
Huang, Guanling
Kurkciyan, Adrianne
Barron, Vivian
Jiang, Dianhua
Noble, Paul W.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2019, 60 (01) : 41 - 48
[15] Involvement of mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) in endothelial dysfunction associated with pulmonary hypertension
Shafiq, Mohammad
Lone, Zahid Rasool
Bharati, Pragya
Singh, Himalaya
Jagavelu, Kumaravelu
Verma, Neeraj Kumar
Ghosh, Jimut Kanti
Gaestel, Matthias
Hanif, Kashif
LIFE SCIENCES, 2021, 286
[16] DBM1285 Suppresses Tumor Necrosis Factor α Production by Blocking p38 Mitogen-Activated Protein Kinase/Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Signaling Pathway
Kang, Jong Soon
Kim, Hwan Mook
Choi, In Young
Han, Sang-Bae
Yoon, Yeo Dae
Lee, Hyunju
Park, Ki Hwan
Cho, Ig Jun
Lee, Chang Woo
Lee, Kiho
Lee, Ki Hoon
Park, Song-Kyu
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2010, 334 (02) : 657 - 664
[17] Mitogen-activated protein kinase 2 regulates physiological and pathological bone turnover
Braun, Tobias
Lepper, Johannes
Heiland, Gisela Ruiz
Hofstetter, Willy
Siegrist, Mark
Lezuo, Patrick
Gaestel, Matthias
Rumpler, Monika
Thaler, Roman
Klaushofer, Klaus
Distler, Joerg H. W.
Schett, Georg
Zwerina, Jochen
JOURNAL OF BONE AND MINERAL RESEARCH, 2013, 28 (04) : 936 - 947
[18] The Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in the p38/TNF-α Pathway of Systemic and Cutaneous Inflammation
Schottelius, Arndt J.
Zuegel, Ulrich
Doecke, Wolf-Dietrich
Zollner, Thomas M.
Roese, Lars
Mengel, Anne
Buchmann, Bernd
Becker, Andreas
Gruetz, Gerald
Naundorf, Sandra
Friedrich, Anke
Gaestel, Matthias
Asadullah, Khusru
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2010, 130 (02) : 481 - 491
[19] Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 Deficiency Reduces Insulin Sensitivity in High-Fat Diet-Fed Mice
de Boer, Jan Freark
Dikkers, Arne
Jurdzinski, Angelika
von Felden, Johann
Gaestel, Matthias
Bavendiek, Udo
Tietge, Uwe J. F.
PLOS ONE, 2014, 9 (09):
[20] Computation of pharmacophore models for the prediction of mitogen-activated protein kinase activated protein kinase-2 inhibitory activity of pyrrolopyridines
Kaushik, Upasna
Sharma, Vikas
Kumar, Vipin
MEDICINAL CHEMISTRY RESEARCH, 2012, 21 (11) : 3777 - 3784

← 1 2 3 4 5 →