Discovery and Characterization of ACT-335827, an Orally Available, Brain Penetrant Orexin Receptor Type1 Selective Antagonist

被引：74
|
作者：
Steiner, Michel A. [1 ]
Gatfield, John [1 ]
Brisbare-Roch, Catherine [1 ]
Dietrich, Hendrik [1 ]
Treiber, Alexander [1 ]
Jenck, Francois [1 ]
Boss, Christoph [1 ]
机构：
[1] Actel Pharmaceut Ltd, CH-4123 Allschwil, Switzerland
来源：
CHEMMEDCHEM | 2013年 / 8卷 / 06期
关键词：
anxiety; neurotransmitters; orexin receptor antagonists; peptides; sleep; SLEEP; PROMOTION; SYSTEM;
D O I：
10.1002/cmdc.201300003
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Stress relief: Orexin neuropeptides regulate arousal and stress processing through orexin receptor type1 (OXR-1) and 2 (OXR-2) signaling. A selective OXR-1 antagonist, represented by a phenylglycine-amide substituted tetrahydropapaverine derivative (ACT-335827), is described that is orally available, penetrates the brain, and decreases fear, compulsive behaviors and autonomic stress reactions in rats. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
引用
收藏
页码：898 / 903
页数：6
相关论文
共 50 条
  • [1] The selective orexin receptor 1 antagonist ACT-335827 in a rat model of diet-induced obesity associated with metabolic syndrome
    Steiner, Michel A.
    Sciarretta, Carla
    Pasquali, Anne
    Jenck, Francois
    FRONTIERS IN PHARMACOLOGY, 2013, 4
  • [2] Characterization of a novel brain penetrant, orally available corticotropin-releasing hormone receptor 1 (CRH-R1) antagonist for treatment of alcoholism
    Thorsell, Annika
    Cippitelli, Andrea
    Ciccocioppo, Roberto
    Heilig, Markus
    NEUROPSYCHOPHARMACOLOGY, 2006, 31 : S73 - S74
  • [3] Structure-Activity Relationship, Biological, and Pharmacological Characterization of the Proline Sulfonamide ACT-462206: a Potent, Brain-Penetrant Dual Orexin 1/Orexin 2 Receptor Antagonist
    Boss, Christoph
    Roch-Brisbare, Catherine
    Steiner, Michel A.
    Treiber, Alexander
    Dietrich, Hendrik
    Jenck, Francois
    von Raumer, Markus
    Sifferlen, Thierry
    Brotschi, Christine
    Heidmann, Bibia
    Williams, Jodi T.
    Aissaoui, Hamed
    Siegrist, Romain
    Gatfield, John
    CHEMMEDCHEM, 2014, 9 (11) : 2486 - 2496
  • [4] Structure-activity-relationship, biological and pharmacological characterization of the proline sulfonamide ACT-462206, a highly potent, brain penetrant dual orexin 1/orexin 2 receptor antagonist
    Boss, Christoph
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2014, 248
  • [5] Discovery of the Potent, Selective, Orally Available CXCR7 Antagonist ACT-1004-1239
    Richard-Bildstein, Sylvia
    Aissaoui, Hamed
    Pothier, Julien
    Schafer, Gabriel
    Gnerre, Carmela
    Lindenberg, Eleanor
    Lehembre, Francois
    Pouzol, Laetitia
    Guerry, Philippe
    JOURNAL OF MEDICINAL CHEMISTRY, 2020, 63 (24) : 15864 - 15882
  • [6] Discovery of TAK-925 as a Potent, Selective, and Brain-Penetrant Orexin 2 Receptor Agonist
    Fujimoto, Tatsuhiko
    Rikimaru, Kentaro
    Fukuda, Koichiro
    Sugimoto, Hiromichi
    Masuda, Kei
    Ohyabu, Norio
    Banno, Yoshihiro
    Tokunaga, Norihito
    Kawamoto, Tetsuji
    Tomata, Yoshihide
    Kumagai, Yasumi
    Iida, Motoo
    Nagano, Yoichi
    Yoneyama-Hirozane, Mariko
    Shimizu, Yuji
    Sasa, Katsunori
    Ishikawa, Takashi
    Yukitake, Hiroshi
    Ito, Mitsuhiro
    Aoyama, Kazunobu
    Matsumoto, Takahiro
    ACS MEDICINAL CHEMISTRY LETTERS, 2022, 13 (03): : 457 - 462
  • [7] In vivo Characterization of a Selective, Orally Available, and Brain Penetrant Small Molecule GPR139 Agonist
    Shoblock, James R.
    Welty, Natalie
    Fraser, Ian
    Wyatt, Ryan
    Lord, Brian
    Lovenberg, Timothy
    Liu, Changlu
    Bonaventure, Pascal
    FRONTIERS IN PHARMACOLOGY, 2019, 10
  • [8] Discovery of JNJ-61393215: Selective orexin-1 receptor antagonist
    Lebold, Terry
    Gelin, Christine
    Preville, Cathy
    Ziff, Jeannie
    Coate, Heather
    Dvorak, Curt
    Bonaventure, Pascal
    Koudriakova, Tatiana
    Lord, Brian
    Nepomuceno, Diane
    Rizzolio, Michele
    Coe, Kevin
    Ndifor, Anthony
    Dugovic, Christine
    Shelton, Jonathan
    Pippel, Daniel
    Lovenberg, Timothy
    Carruthers, Nicholas
    Shireman, Brock
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2019, 258
  • [9] Discovery of an Orally Available, Brain Penetrant BACE1 Inhibitor That Affords Robust CNS Aβ Reduction
    Stamford, Andrew W.
    Scott, Jack D.
    Li, Sarah W.
    Babu, Suresh
    Tadesse, Dawit
    Hunter, Rachael
    Wu, Yusheng
    Misiaszek, Jeffrey
    Cumming, Jared N.
    Gilbert, Eric J.
    Huang, Chunli
    McKittrick, Brian A.
    Hong, Liwu
    Guo, Tao
    Zhu, Zhaoning
    Strickland, Corey
    Orth, Peter
    Voigt, Johannes H.
    Kennedy, Matthew E.
    Chen, Xia
    Kuvelkar, Reshma
    Hodgson, Robert
    Hyde, Lynn A.
    Cox, Kathleen
    Favreau, Leonard
    Parker, Eric M.
    Greenlee, William J.
    ACS MEDICINAL CHEMISTRY LETTERS, 2012, 3 (11): : 897 - 902
  • [10] MTIP: A novel brain penetrant, orally available corticotropin-releasing hormone receptor 1 (CRH-R1) antagonist for treatment of alcoholism
    Gehlert, D. R.
    Cippitelli, A.
    Thorsell, A.
    Le, A. D.
    Hipskind, P. A.
    Hamdouchi, C.
    Lu, J.
    Hembre, E. J.
    Cramer, J.
    Song, M.
    McKinzie, D.
    Morin, M.
    Ciccocioppo, R.
    Heilig, M.
    NEUROPEPTIDES, 2008, 42 (01) : 117 - 117
12345