BN/CC isosterism in borazaronaphthalenes towards phosphodiesterase 10A (PDE10A) inhibitors

被引：58
|
作者：
Vlasceanu, Alexandru [3 ]
Jessing, Mikkel [1 ,2 ]
Kilburn, John Paul [1 ,2 ]
机构：
[1] H Lundbeck & Co AS, Discovery Chem, DK-2500 Valby, Denmark
[2] H Lundbeck & Co AS, DMPK, DK-2500 Valby, Denmark
[3] Univ Copenhagen, Dept Chem, DK-2100 Copenhagen, Denmark
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2015年 / 23卷 / 15期
关键词：
Borazaronaphthalenes; PDE10A inhibitors; Antipsychotics; HETEROAROMATIC-COMPOUNDS; ENZYME-INHIBITORS; BORON COMPOUNDS; B-N; SCHIZOPHRENIA; 2,1-BORAZARONAPHTHALENES; SUBSTITUTION; DERIVATIVES; CHEMISTRY; DISCOVERY;
D O I：
10.1016/j.bmc.2015.06.019
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The application of BN/CC isosterism is explored as a method of expanding the scope of core scaffolds in biologically active compounds. The viability of potential drug candidates incorporating BN-heteroaromatic moieties was investigated through the synthesis of BN-substituted analogs to known phosphodiesterase (PDE10A) inhibitors, namely MP10 and a selection of N-methylanilide analogs. These in some cases revealed unexpectedly potent and relatively stable derivatives, providing further support for the potential of BN-incorporation in medicinal chemistry. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4453 / 4461
页数：9
相关论文
共 50 条
  • [1] Triazoloquinazolines as a novel class of phosphodiesterase 10A (PDE10A) inhibitors
    Kehler, Jan
    Ritzen, Andreas
    Langgard, Morten
    Petersen, Sebastian Leth
    Farah, Mohamed M.
    Bundgaard, Christoffer
    Christoffersen, Claus Tornby
    Nielsen, Jacob
    Kilburn, John Paul
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (12) : 3738 - 3742
  • [2] Translational pharmacodynamics of phosphodiesterase 10A (PDE10A) inhibitors for treatment of schizophrenia
    Nielsen, J.
    Steiniger-Brach, B.
    INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 2012, 15 : 32 - 33
  • [3] Phosphodiesterase 10A (PDE10A) and psychosis: Studies using the PDE10A inhibitor papaverine and PDE10A knockout mice
    Siuciak, JA
    Chapin, DS
    McCarthy, SA
    SCHIZOPHRENIA BULLETIN, 2005, 31 (02) : 310 - 310
  • [4] Current Landscape of Phosphodiesterase 10A (PDE10A) Inhibition
    Chappie, Thomas A.
    Helal, Christopher J.
    Hou, Xinjun
    JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (17) : 7299 - 7331
  • [5] Discovery and SAR exploration of quinazoline and cyanoisoquinoline inhibitors of Phosphodiesterase 10A (PDE10A)
    Kehler, Jan
    Nielsen, Jacob
    Christoffersen, Claus Tornby
    Ritzen, Andreas
    Langgard, Morten
    Steiniger-Brach, Bjorn
    Kreilgaard, Mads
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2012, 243
  • [6] Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability
    Chino, Ayaka
    Masuda, Naoyuki
    Amano, Yasushi
    Honbou, Kazuya
    Mihara, Takuma
    Yamazaki, Mayako
    Tomishima, Masaki
    BIOORGANIC & MEDICINAL CHEMISTRY, 2014, 22 (13) : 3515 - 3526
  • [7] Benzothiophene derivatives as phosphodiesterase 10A (PDE10A) inhibitors: Hit-to-lead studies
    Kawamoto, Yoshito
    Tomino, Minako
    Hiramatsu, Kenichi
    Oyama, Yoshiaki
    Hayashi, Yasuhiro
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2019, 29 (11) : 1419 - 1422
  • [8] Medicinal chemistry strategies for the development of phosphodiesterase 10A (PDE10A) inhibitors - An update of recent progress
    Amin, Harsh S.
    Parikh, Palak K.
    Ghate, Manjunath D.
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2021, 214
  • [9] N-Methylanilide and N-methylbenzamide derivatives as phosphodiesterase 10A (PDE10A) inhibitors
    Kilburn, John Paul
    Kehler, Jan
    Langgard, Morten
    Erichsen, Mette N.
    Leth-Petersen, Sebastian
    Larsen, Mogens
    Christoffersen, Claus Tornby
    Nielsen, Jacob
    BIOORGANIC & MEDICINAL CHEMISTRY, 2013, 21 (19) : 6053 - 6062
  • [10] Rapid Identification of a Novel Small Molecule Phosphodiesterase 10A (PDE10A) Tracer
    Hu, Essa
    Ma, Ji
    Biorn, Christopher
    Lester-Zeiner, Dianna
    Cho, Robert
    Rumfelt, Shannon
    Kunz, Roxanne K.
    Nixey, Thomas
    Michelsen, Klaus
    Miller, Silke
    Shi, Jianxia
    Wong, Jamie
    Della Puppa, Geraldine Hill
    Able, Jessica
    Talreja, Santosh
    Hwang, Dah-Ren
    Hitchcock, Stephen A.
    Porter, Amy
    Immke, David
    Allen, Jennifer R.
    Treanor, James
    Chen, Hang
    JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (10) : 4776 - 4787
12345