Discovery of potent and selective succinyl hydroxamate inhibitors of matrix metalloprotease-3 (stromelysin-1)

被引：24
|
作者：
Fray, MJ [1 ]
Dickinson, RP [1 ]
机构：
[1] Pfizer Global Res & Dev, Dept Discovery Chem, Sandwich CT13 9NJ, Kent, England
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 04期
关键词：
D O I：
10.1016/S0960-894X(00)00720-4
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Structure-activity relationships are described for a series of succinyl hydroxamic acids 4a-o as potent and selective inhibitors of matrix metalloprotease-3 (stromelysin-1). Optimisation of P1' and P3' groups gave compound 4j (MMP-3 IC50 = 5.9nM) which was >140-fold less potent against MMP-1 (IC50 = 51,000nM), MMP-2 (IC50=1790nM), MMP-9 (IC50 = 840 nM) and MMP-14 (IC50 = 1900 nM). (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：571 / 574
页数：4
相关论文
共 50 条
  • [41] Discovery and optimization of potent, selective, and orally bioavailable Jak1 inhibitors
    Zak, Mark
    Johnson, Adam
    Van Abbema, Anne
    Waszkowycz, Bohdan
    Eigenbrot, Charles
    Chang, Christine
    Hurley, Christopher
    Hanan, Emily
    Kenny, Jane
    Kulagowski, Janusz
    DeVoss, Jason
    Murray, Jeremy
    Balazs, Mercedesz
    Steffek, Micah
    Koehler, Michael
    Ghilardi, Nico
    Chakravarty, Paroma
    Lupardus, Patrick
    Gibbons, Paul
    Dragovich, Peter
    Bergeron, Philippe
    Pulk, Rebecca
    Mendonca, Rohan
    Savage, Scott
    Labadie, Sharada
    Gradl, Stefan
    Ward, Stuart
    Blair, Wade
    Jia, Wei
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2012, 243
  • [42] Discovery of selective potent TBK1and IKKe dual kinase inhibitors
    Gingipalli, Lakshmaiah
    Chuaqui, Claudio
    Cowen, Scott
    Jeffrey, Johannes
    Devereauxa, Erik
    Molina, Audrey
    Wang, Tao
    Whitstonb, David
    Wu, Xiaoyun
    Zhang, Hai-Jun
    Zinda, Michael
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2015, 250
  • [43] Interleukin-17F affects cartilage matrix turnover by increasing the expression of collagenases and stromelysin-1 and by decreasing the expression of their inhibitors and extracellular matrix components in chondrocytes
    Tanigawa, Shihoko
    Aida, Yukiko
    Kawato, Takayuki
    Honda, Kazuhiro
    Nakayama, Go
    Motohashi, Masafumi
    Suzuki, Naoto
    Ochiai, Kuniyasu
    Matsumura, Hideo
    Maeno, Masao
    CYTOKINE, 2011, 56 (02) : 376 - 386
  • [44] Stromelysin-1/matrix metalloproteinase-3 (MMP-3) expression accounts for invasive properties of human astrocytoma cell lines
    Mercapide, J
    De Cicco, RL
    Castresana, JS
    Klein-Szanto, AJP
    INTERNATIONAL JOURNAL OF CANCER, 2003, 106 (05) : 676 - 682
  • [45] Discovery of Potent and Selective Allosteric Inhibitors of Protein Arginine Methyltransferase 3 (PRMT3)
    Kaniskan, H. Umit
    Eram, Mohammad S.
    Zhao, Kehao
    Szewczyk, Magdalena M.
    Yang, Xiaobao
    Schmidt, Keith
    Luo, Xiao
    Xiao, Sean
    Dai, Miao
    He, Feng
    Zang, Irene
    Lin, Ying
    Li, Fengling
    Dobrovetsky, Elena
    Smil, David
    Min, Sun-Joon
    Lin-Jones, Jennifer
    Schapira, Matthieu
    Atadja, Peter
    Li, En
    Barsyte-Lovejoy, Dalia
    Arrowsmith, Cheryl H.
    Brown, Peter J.
    Liu, Feng
    Yu, Zhengtian
    Vedadi, Masoud
    Jin, Jian
    JOURNAL OF MEDICINAL CHEMISTRY, 2018, 61 (03) : 1204 - 1217
  • [46] Discovery of Pyrazolo[1,5-a]pyridine Derivatives as Potent and Selective PI3Kγ/δ Inhibitors
    Wang, Chun
    Zou, Fengming
    Qi, Ziping
    Liu, Qingwang
    Shen, Lijuan
    Yuan, Xinyu
    Deng, Maoqing
    Wang, Aoli
    Wang, Beilei
    Wang, Li
    Liang, Xiaofei
    Liu, Qingsong
    Liu, Jing
    JOURNAL OF MEDICINAL CHEMISTRY, 2024, 67 (17) : 15199 - 15219
  • [47] Discovery of Potent, Selective, and Orally Active Carboxylic Acid Based Inhibitors of Matrix Metalloproteinase-13
    Monovich, Lauren G.
    Tommasi, Ruben A.
    Fujimoto, Roger A.
    Blancuzzi, Vincent
    Clark, Kirk
    Cornell, Wendy D.
    Doti, Robert
    Doughty, John
    Fang, James
    Farley, David
    Fitt, John
    Ganu, Vishwas
    Goldberg, Ronald
    Goldstein, Robert
    Lavoie, Stacey
    Kulathila, Raviraj
    Macchia, William
    Parker, David T.
    Melton, Richard
    O'Byrne, Elizabeth
    Pastor, Gary
    Pellas, Theodore
    Quadros, Elizabeth
    Reel, Noela
    Roland, Dennis M.
    Sakane, Yumi
    Singh, Hem
    Skiles, Jerry
    Somers, Joseph
    Toscano, Karen
    Wigg, Andrew
    Zhou, Siyuan
    Zhu, Lijuan
    Shieh, Wen-Chung
    Xue, Song
    McQuire, Leslie W.
    JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (11) : 3523 - 3538
  • [48] Discovery of novel pyrazinone derivatives as potent and selective caspase-3 inhibitors.
    Han, YX
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2002, 224 : U81 - U81
  • [49] The discovery of potent and selective kynurenine 3-monooxygenase inhibitors for the treatment of acute pancreatitis
    Liddle, John
    Beaufils, Benjamin
    Binnie, Margaret
    Bouillot, Anne
    Denis, Alexis A.
    Hann, Michael M.
    Haslam, Carl P.
    Holmes, Duncan S.
    Hutchinson, Jon P.
    Kranz, Michael
    McBride, Andrew
    Mirguet, Olivier
    Mole, Damian J.
    Mowat, Christopher G.
    Pal, Sandeep
    Rowland, Paul
    Trottet, Lionel
    Uings, Iain J.
    Walker, Ann L.
    Webster, Scott P.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (09) : 2023 - 2028
  • [50] Discovery of novel aspartyl ketone dipeptides as potent and selective caspase-3 inhibitors
    Giroux, A
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2005, 230 : U3315 - U3315
12345