Discovery and biological profile of isoindolinone derivatives as novel metabotropic glutamate receptor 1 antagonists: A potential treatment for psychotic disorders

被引：56
|
作者：
Ito, Satoru [1 ]
Hirata, Yukari [1 ]
Nagatomi, Yasushi [1 ]
Satoh, Atsushi [1 ]
Suzuki, Gentaroh [1 ]
Kimura, Toshifumi [1 ]
Satow, Akio [1 ]
Maehara, Shunsuke [1 ]
Hikichi, Hirohiko [1 ]
Hata, Mikiko [1 ]
Ohta, Hisashi [1 ]
Kawamoto, Hiroshi [1 ]
机构：
[1] Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 18期
关键词：
mGluR1; Antagonist; Glutamate; Psychotic disorder; GLUTAMATE-RECEPTOR-1; ANTAGONIST; METABOLIC-ACTIVATION; FTIDC;
D O I：
10.1016/j.bmcl.2009.07.145
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
We describe here the discovery and biological profile of a series of isoindolinone derivatives as developed mGluR1 antagonists. Our combined strategy of rapid parallel synthesis and conventional medicinal optimization successfully led to N-cyclopropyl 22 and N-isopropyl isoindolinone analogs 21 and 23 with improved in vivo DMPK profiles. Moreover the most advanced analog 23 showed an oral antipsychotic-like effect at a dose of 1 mg/kg in an animal model. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5310 / 5313
页数：4
相关论文
共 50 条
  • [1] Synthesis and biological evaluation of aryl isoxazole derivatives as metabotropic glutamate receptor 1 antagonists: A potential treatment for neuropathic pain
    Cho, Gyeong Hi
    Kim, TaeHun
    Son, Woo Seung
    Seo, Seon Hee
    Min, Sun-Joon
    Cho, Yong Seo
    Keum, Gyochang
    Jeong, Kyu-Sung
    Koh, Hun Yeong
    Lee, Jiyoun
    Pae, Ae Nim
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (06) : 1324 - 1328
  • [2] Discovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine derivatives as selective metabotropic glutamate receptor 1 antagonists for the potential treatment of neuropathic pain
    Nam, Mina
    Kim, TaeHun
    Kwak, Jinsook
    Seo, Seon Hee
    Ko, Min Kyung
    Lim, Eun Jeong
    Min, Sun-Joon
    Cho, Yong Seo
    Keum, Gyochang
    Baek, Du-Jong
    Lee, Jiyoun
    Pae, Ae Nim
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 97 : 245 - 258
  • [3] Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists
    Kulkarni, Santosh S.
    Newman, Amy Hauck
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (11) : 2987 - 2991
  • [4] Discovery of novel heteroarylazoles that are metabotropic glutamate subtype 5 receptor antagonists with anxiolytic activity
    Roppe, J
    Smith, ND
    Huang, DH
    Tehrani, L
    Wang, BW
    Anderson, J
    Brodkin, J
    Chung, J
    Jiang, XH
    King, C
    Munoz, B
    Varney, MA
    Prasit, P
    Cosford, NDP
    JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (19) : 4645 - 4648
  • [5] Prospects for metabotropic glutamate 1 receptor antagonists in the treatment of neuropathic pain
    Schkeryantz, Jeffrey M.
    Kingston, Ann E.
    Johnson, Michael P.
    JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (11) : 2563 - 2568
  • [6] Discovery of orally efficacious tetracyclic metabotropic glutamate receptor 1 (mGluR1) antagonists for the treatment of chronic pain
    Wu, Wen-Lian
    Burnett, Duane A.
    Domalski, Martin
    Greenlee, William J.
    Li, Cheng
    Bertorelli, Rosalia
    Fredduzzi, Silva
    Lozza, Gianluca
    Veltri, Alessio
    Reggiani, Angelo
    JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (23) : 5550 - 5553
  • [7] A novel series of potent and selective noncompetitive antagonists of metabotropic glutamate receptor 1
    Li, L
    Tomlinson, R
    Wang, Y
    Tsui, HCT
    Chamberlain, MJ
    Johnson, MP
    Baez, M
    Vannieuwenhze, MS
    Zia-Ebrahimi, M
    Hong, EJ
    Schkeryantz, JM
    Monn, JA
    Porter, WJ
    Baker, SR
    Owton, WM
    Clark, BP
    Kingston, AE
    NEUROPHARMACOLOGY, 2002, 43 (02) : 295 - 295
  • [8] MEDI 472-Synthesis and biological evaluation of novel thiazolo[3,2-a]benzimidazole derivatives as metabotropic glutamate receptor 1 antagonists
    Fujiyasu, Jiro
    Itahana, Hirotsune
    Okada, Masamichi
    Toya, Takashi
    Watanabe, Toshihiro
    Okada, Minoru
    Ohta, Mitsuaki
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2006, 232
  • [9] In vitro pharmacological characterization of novel isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists
    Suzuki, Gentaroh
    Tsukamoto, Naohiro
    Fushiki, Hiroshi
    Kawagishi, Aki
    Nakamura, Masayuki
    Kurihara, Hideki
    Mitsuya, Morihiro
    Ohkubo, Mitsuru
    Ohta, Hisashi
    JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2007, 323 (01): : 147 - 156
  • [10] Discovery and biological profile of a new class of metabotropic receptor 1 allosteric antagonist
    Itoh, S
    Satoh, A
    Nagatomi, Y
    Hirata, Y
    Suzuki, G
    Kimura, T
    Satow, A
    Hata, M
    Kawamoto, H
    Ohta, H
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2005, 230 : U2533 - U2533
12345