Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors

被引：67
|
作者：
Xin, Zhili [1 ]
Zhao, Hongyu [1 ]
Serby, Michael D. [1 ]
Liu, Bo [1 ]
Liu, Mei [1 ]
Szczepankiewicz, Bruce G. [1 ]
Nelson, Lissa T. J. [1 ]
Smith, Harriet T. [1 ]
Suhar, Tom S. [1 ]
Janis, Rich S. [1 ]
Cao, Ning [1 ]
Camp, Heidi S. [1 ]
Collins, Christine A. [1 ]
Sham, Hing L. [1 ]
Surowy, Teresa K. [1 ]
Liu, Gang [1 ]
机构：
[1] Abbott Labs, Global Pharmaceut Res & Dev, Abbott Pk, IL 60064 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 15期
关键词：
SCD1; inhibitors; desaturation index;
D O I：
10.1016/j.bmcl.2008.06.088
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of structurally novel stearoyl-CoA desaturase1 (SCD1) inhibitors has been identified via molecular scaffold manipulation. Preliminary structure-activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(methyl carbamoyl)phenyl]piperidine-1-carboxamide 4c exhibited robust in vivo activity with dose-dependent desaturation index lowering effects. (c) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4298 / 4302
页数：5
相关论文
共 50 条
  • [31] Mechanism of Electron Transport in Mammalian Stearoyl-Coa Desaturase 1
    Shen, Jiemin
    Wu, Gang
    Tsai, Ah-Lim
    Zhou, Ming
    BIOPHYSICAL JOURNAL, 2021, 120 (03) : 305A - 305A
  • [32] Discovery of Piperazin-1-ylpyridazine-Based Potent and Selective Stearoyl-CoA Desaturase-1 Inhibitors for the Treatment of Obesity and Metabolic Syndrome
    Zhang, Zaihui
    Sun, Shaoyi
    Kodumuru, Vishnumurthy
    Hou, Duanjie
    Liu, Shifeng
    Chakka, Nagasree
    Sviridov, Serguei
    Chowdhury, Sultan
    McLaren, David G.
    Ratkay, Leslie G.
    Khakh, Kuldip
    Cheng, Xing
    Gschwend, Heinz W.
    Kamboj, Rajender
    Fu, Jianmin
    Winther, Michael D.
    JOURNAL OF MEDICINAL CHEMISTRY, 2013, 56 (02) : 568 - 583
  • [33] Lack of stearoyl-CoA desaturase-1 function induces a palmitoyl-CoA Δ6 desaturase and represses the stearoyl-CoA desaturase-3 gene in the preputial glands of the mouse
    Miyazaki, M
    Gomez, FE
    Ntambi, JM
    JOURNAL OF LIPID RESEARCH, 2002, 43 (12) : 2146 - 2154
  • [34] Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer
    Tracz-Gaszewska, Zuzanna
    Dobrzyn, Pawel
    CANCERS, 2019, 11 (07)
  • [35] Regulation of hepatic stearoyl-CoA desaturase gene 1 by vitamin A
    Miller, CW
    Waters, KM
    Ntambi, JM
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 231 (01) : 206 - 210
  • [36] Stearoyl-CoA desaturase-1 and adaptive stress signaling
    Koeberle, Andreas
    Loeser, Konstantin
    Thuermer, Maria
    BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2016, 1861 (11): : 1719 - 1726
  • [37] DISCOVERY OF NOVEL STEAROYL COA DESATURASE ENZYME 1 (SCD1) INHIBITORS
    Le Roy, Isabelle
    Passelaigue, Elisabeth Dupont
    Bressanges, Christelle
    Roy, Anne-Cecile
    Junquero, Didier
    Rival, Yves
    Valeille, Karine
    DRUGS OF THE FUTURE, 2009, 34 : 85 - 85
  • [38] Orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors
    Koltun, Dmitry O.
    Vasilevich, Natalya I.
    Parkhill, Eric Q.
    Glushkov, Andrei I.
    Zilbershtein, Timur M.
    Mayboroda, Elena I.
    Boze, Melanie A.
    Cole, Andrew G.
    Henderson, Ian
    Zautke, Nathan A.
    Brunn, Sandra A.
    Chu, Nancy
    Hao, Jia
    Mollova, Nevena
    Leung, Kwan
    Chisholm, Jeffrey W.
    Zablocki, Jeff
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (11) : 3050 - 3053
  • [39] Novel, potent, selective, and metabolically stable stearoyl-CoA desaturase (SCD) inhibitors
    Koltun, Dmitry O.
    Parkhill, Eric Q.
    Vasilevich, Natalya I.
    Glushkov, Andrei I.
    Zilbershtein, Timur M.
    Ivanov, Alexei V.
    Cole, Andrew G.
    Henderson, Ian
    Zautke, Nathan A.
    Brunn, Sandra A.
    Mollova, Nevena
    Leung, Kwan
    Chisholm, Jeffrey W.
    Zablocki, Jeff
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (07) : 2048 - 2052
  • [40] Expression and regulation of Δ5-desaturase, Δ6-desaturase, stearoyl-coenzyme A (CoA) desaturase 1, and stearoyl-CoA desaturase 2 in rat testis
    Sæther, T
    Tran, TN
    Rootwelt, H
    Christophersen, BO
    Haugen, TB
    BIOLOGY OF REPRODUCTION, 2003, 69 (01) : 117 - 124
12345