Pyrazole derived from (+)-3-carene; a novel potent, selective scaffold for sphingosine-1-phosphate (S1P1) receptor agonists

被引：8
|
作者：
Zecri, Frederic J. [1 ]
Albert, Rainer
Landrum, Gregory [1 ]
Hinterding, Klaus [2 ]
Cooke, Nigel G. [1 ]
Guerini, Danilo [1 ]
Streiff, Markus [1 ]
Bruns, Christian [1 ]
Nuesslein-Hildesheim, Barbara [1 ]
机构：
[1] Novartis Inst BioMed Res, CH-4056 Basel, Switzerland
[2] F Hoffmann La Roche Ltd, CH-4070 Basel, Switzerland
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 01期
关键词：
S1P(1) agonist; Carene; Pharmacophore model; LIGAND-BINDING POCKET; SPHINGOSINE; 1-PHOSPHATE; 3-ARYLPROPIONIC ACIDS; LYMPHOCYTE EGRESS; IDENTIFICATION; MODULATORS; DISCOVERY; AFFINITY; SUBTYPES; FTY720;
D O I：
10.1016/j.bmcl.2009.11.045
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
High throughput screening and hit to lead optimization led to the identification of 'carene' as a promising scaffold showing selective S1P(1) receptor agonism. In parallel to this work we have established a pharmacophore model for the S1P(1) receptor highlighting the minimal structural requirement necessary for potent receptor agonism. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码：35 / 37
页数：3
相关论文
共 50 条
  • [31] Pharmacophore-based design of novel oxadiazoles as selective sphingosine-1-phosphate (S1P) receptor agonists with in vivo efficacy
    Quattropani, Anna
    Sauer, Wolfgang
    Crosignani, Stefano
    Dorbais, Jerome
    Gerber, Patrick
    Gonzalez, Jerome
    Marin, Delphine
    Muzerelle, Mathilde
    Beltran, Fanny
    Nichols, Anthony
    Georgi, Katrin
    Schneider, Manfred
    Vitte, Pierre-Alain
    Eligert, Valerie
    Novo-Perez, Laurence
    Hantson, Jennifer
    Nock, Sebastien
    Carboni, Susanna
    de Souza, Adriano Soares
    Arrighi, Jean-Francois
    Boschert, Ursula
    Bombrun, Agnes
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2015, 250
  • [32] Aryl Ether-Derived Sphingosine-1-Phosphate Receptor (S1P1) Modulators: Optimization of the PK, PD, and Safety Profiles
    Xiao, Zili
    Yang, Michael G.
    Dhar, T. G. Murali
    Xiao, Hai-Yun
    Gilmore, John L.
    Marcoux, David
    McIntyre, Kim W.
    Taylor, Tracy L.
    Shi, Hong
    Levesque, Paul C.
    Marino, Anthony M.
    Cornelius, Georgia
    Mathur, Arvind
    Shen, Ding Ren
    Cvijic, Mary Ellen
    Lehman-McKeeman, Lois D.
    Sun, Huadong
    Xie, Jenny H.
    Carter, Percy H.
    Dyckman, Alaric J.
    ACS MEDICINAL CHEMISTRY LETTERS, 2020, 11 (09): : 1766 - 1772
  • [33] Pharmacophore-Based Design of Novel Oxadiazoles as Selective Sphingosine-1-phosphate (S1P) Receptor Agonists with in vivo Efficacy
    Quattropani, Anna
    Sauer, Wolfgang H. B.
    Crosignani, Stefano
    Dorbais, Jerome
    Gerber, Patrick
    Gonzalez, Jerome
    Marin, Delphine
    Muzerelle, Mathilde
    Beltran, Fanny
    Nichols, Anthony
    Georgi, Katrin
    Schneider, Manfred
    Vitte, Pierre-Alain
    Eligert, Valerie
    Novo-Perez, Laurence
    Hantson, Jennifer
    Nock, Sebastien
    Carboni, Susanna
    de Souza, Adriano Luis Soares
    Arrighi, Jean-Francois
    Boschert, Ursula
    Bombrun, Agnes
    CHEMMEDCHEM, 2015, 10 (04) : 688 - 714
  • [34] Exploring amino acids derivatives as potent, selective, and direct agonists of sphingosine-1-phosphate receptor subtype-1
    Evindar, Ghotas
    Deng, Hongfeng
    Bernier, Sylvie G.
    Doyle, Elisabeth
    Lorusso, Jeanine
    Morgan, Barry A.
    Westlin, William F.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (02) : 472 - 475
  • [35] Discovery of a novel series of potent S1P1 agonists
    Crosignani, Stefano
    Bombrun, Agnes
    Covini, David
    Maio, Maurizio
    Marin, Delphine
    Quattropani, Anna
    Swinnen, Dominique
    Simpson, Don
    Sauer, Wolfgang
    Francon, Bernard
    Martin, Thierry
    Cambet, Yves
    Nichols, Anthony
    Martinou, Isabelle
    Burgat-Charvillon, Fabienne
    Rivron, Delphine
    Donini, Cristina
    Schott, Olivier
    Eligert, Valerie
    Novo-Perez, Laurence
    Vitte, Pierre-Alain
    Arrighi, Jean-Francois
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (05) : 1516 - 1519
  • [36] Design, synthesis and docking-based 3D-QSAR study of novel 2-substituted 2-aminopropane-1,3-diols as potent and selective agonists of sphingosine-1-phosphate 1 (S1P1) receptor
    Tian, Yulin
    Jin, Jing
    Wang, Xiaojian
    Han, Weijuan
    Li, Gang
    Zhou, Wanqi
    Xiao, Qiong
    Qi, Jianguo
    Chen, Xiaoguang
    Yin, Dali
    MEDCHEMCOMM, 2013, 4 (09) : 1267 - 1274
  • [37] Design and synthesis of selective sphingosine-1-phosphate receptor 1 agonists with increased phosphorylation rates
    Qiong Xiao
    Minwan Hu
    Si Chen
    Yifan Tang
    Zeyu Shi
    Jing Jin
    Jinping Hu
    Ping Xie
    Dali Yin
    Acta Pharmaceutica Sinica B, 2020, 10 (06) : 1134 - 1142
  • [38] Novel S1P1 Receptor Agonists - Part 3: From Thiophenes to Pyridines
    Bolli, Martin H.
    Abele, Stefan
    Birker, Magdalena
    Bravo, Roberto
    Bur, Daniel
    de Kanter, Ruben
    Kohl, Christopher
    Grimont, Julien
    Hess, Patrick
    Lescop, Cyrille
    Mathys, Boris
    Mueller, Claus
    Nayler, Oliver
    Rey, Markus
    Scherz, Michael
    Schmidt, Gunther
    Seifert, Juergen
    Steiner, Beat
    Velker, Joerg
    Weller, Thomas
    JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (01) : 110 - 130
  • [39] Design and synthesis of selective sphingosine-1-phosphate receptor 1 agonists with increased phosphorylation rates
    Xiao, Qiong
    Hu, Minwan
    Chen, Si
    Tang, Yifan
    Shi, Zeyu
    Jin, Jing
    Hu, Jinping
    Xie, Ping
    Yin, Dali
    ACTA PHARMACEUTICA SINICA B, 2020, 10 (06) : 1134 - 1142
  • [40] SPHINGOSINE-1-PHOSPHATE RECEPTORS S1P1 AND S1P3 REGULATE THE TRANSENDOTHELIAL TRANSPORT OF HDL AND LDL ANTAGONISTICALLY
    Velagapudi, Srividya
    Yalcinkaya, Mustafa
    Rohrer, Lucia
    von Eckardstein, Arnold
    ATHEROSCLEROSIS SUPPLEMENTS, 2018, 32 : 125 - 125
12345