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

[1] Design, synthesis, and biological evaluation of aminopyrazine derivatives as inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2)
Lin, Songnian
Malkani, Sunita
Lombardo, Matthew
Yang, Lihu
Mills, Sander G.
Chapman, Kevin
Thompson, James E.
Zhang, Wen Xiao
Wang, Ruixiu
Cubbon, Rose M.
O'Neill, Edward A.
Hale, Jeffrey J.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (22) : 5402 - 5408
[2] Aminocyanopyridine inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)
Anderson, DR
Hegde, S
Reinhard, E
Gomez, L
Vernier, WF
Lee, L
Liu, S
Sambandam, A
Snider, PA
Masih, L
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (06) : 1587 - 1590
[3] Novel tetrahydro-β-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2)
Trujillo, John I.
Meyers, Marvin J.
Anderson, David R.
Hegde, Shridhar
Mahoney, Matthew W.
Vernier, William F.
Buchler, Ingrid P.
Wu, Kun K.
Yang, Syaluan
Hartmann, Susan J.
Reitz, David B.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (16) : 4657 - 4663
[4] Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) in Skeletal Muscle Atrophy and Hypertrophy
Norrby, Marlene
Tagerud, Sven
JOURNAL OF CELLULAR PHYSIOLOGY, 2010, 223 (01) : 194 - 201
[5] 4-Anilino-6-phenyl-quinoline inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2)
Olsson, Henric
Sjo, Peter
Ersoy, Oguz
Kristoffersson, Anna
Larsson, Joakim
Norden, Bo
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (16) : 4738 - 4740
[6] Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) Contributes to Secondary Damage after Spinal Cord Injury
Ghasemlou, Nader
Lopez-Vales, Ruben
Lachance, ClauDe
Thuraisingam, Thusanth
Gaestel, Matthias
Radzioch, Danuta
David, Samuel
JOURNAL OF NEUROSCIENCE, 2010, 30 (41) : 13750 - 13759
[7] Pivotal Role of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 in Inflammatory Pulmonary Diseases
Qian, Feng
Deng, Jing
Wang, Gang
Ye, Richard D.
Christman, John W.
CURRENT PROTEIN & PEPTIDE SCIENCE, 2016, 17 (04) : 332 - 342
[8] Novel Therapeutic Potential of Mitogen-Activated Protein Kinase Activated Protein Kinase 2 (MK2) in Chronic Airway Inflammatory Disorders
Singh, Rakesh Kumar
Najmi, Abul Kalam
CURRENT DRUG TARGETS, 2019, 20 (04) : 367 - 379
[9] Mitogen-activated protein kinase-activated protein kinase-2 (MK2) and its role in cell survival, inflammatory signaling, and migration in promoting cancer
Morgan, Deri
Berggren, Kiersten L.
Spiess, Colby D.
Smith, Hannah M.
Tejwani, Ajay
Weir, Scott J.
Lominska, Christopher E.
Thomas, Sufi M.
Gan, Gregory N.
MOLECULAR CARCINOGENESIS, 2022, 61 (02) : 173 - 199
[10] Silencing Mitogen-Activated Protein Kinase-Activated Protein Kinase-2 Arrests Inflammatory Bone Loss
Li, Qiyan
Yu, Hong
Zinna, Robert
Martin, Kylie
Herbert, Bethany
Liu, Angen
Rossa, Carlos, Jr.
Kirkwood, Keith L.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2011, 336 (03) : 633 - 642

← 1 2 3 4 5 →