Potent tricyclic pyrazole tetrazole agonists of the nicotinic acid receptor (GPR109a)

被引：29
|
作者：
Boatman, P. Douglas [1 ]
Schrader, Thomas O. [1 ]
Kasem, Michelle [1 ]
Johnson, Benjamin R. [1 ]
Skinner, Philip J. [1 ]
Jung, Jae-Kyu [1 ]
Xu, Jerry [1 ]
Cherrier, Martin C. [1 ]
Webb, Peter J. [1 ]
Semple, Graeme [1 ]
Sage, Carleton R. [1 ]
Knudsen, Jens [1 ]
Chen, Ruoping [2 ]
Taggart, Andrew K. [3 ]
Carballo-Jane, Ester [3 ]
Richman, Jeremy G. [2 ]
机构：
[1] Arena Pharmaceut, Dept Med Chem, San Diego, CA 92121 USA
[2] Arena Pharmaceut, Dept Discovery Biol, San Diego, CA 92121 USA
[3] Merck Res Labs, Rahway, NJ USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 09期
关键词：
Niacin receptor; Free fatty acids; Vasodilation; Atherosclerosis; TERMINAL EPOXIDES; PROSTAGLANDIN D-2; LANGERHANS CELLS; NIACIN; MK-0354; DISEASE; HUMANS; DRUG; MICE;
D O I：
10.1016/j.bmcl.2010.03.062
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Tricyclic pyrazole tetrazoles which are potent partial agonists of the high affinity niacin receptor, GPR109a, have been discovered and optimized. One of these compounds has proven to be effective at lowering free fatty acids in vitro and in vivo. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2797 / 2800
页数：4
相关论文
共 49 条
  • [1] Fluorinated pyrazole acids are agonists of the high affinity niacin receptor GPR109a
    Skinner, Philip J.
    Cherrier, Martin C.
    Webb, Peter J.
    Shin, Young-Jun
    Gharbaoui, Tawfik
    Lindstrom, Andrew
    Hong, Vu
    Tamura, Susan Y.
    Dang, Huong T.
    Pride, Cameron C.
    Chen, Ruoping
    Richman, Jeremy G.
    Connolly, Daniel T.
    Semple, Graeme
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (20) : 5620 - 5623
  • [2] Discovery of novel pyrrole derivatives as potent agonists for the niacin receptor GPR109A
    Miyazawa, Yuriko
    Yamaguchi, Takahiro
    Yamaguchi, Mitsuhiro
    Tago, Keiko
    Tamura, Akihiro
    Sugiyama, Daisuke
    Aburatani, Takahide
    Nishizawa, Tomohiro
    Kurikawa, Nobuya
    Kono, Keita
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2020, 30 (10)
  • [3] Acyl hydroxypyrazoles as novel agonists for high-affinity nicotinic acid receptor GPR109A: WO2008051403
    Shen, Hong C.
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2009, 19 (08) : 1149 - 1155
  • [4] GPR109a agonists. Part 2: Pyrazole-acids as agonists of the human orphan G-protein coupled receptor GPR109a
    Imbriglio, Jason E.
    Chang, Sookhee
    Liang, Rui
    Raghavan, Subharekha
    Schmidt, Darby
    Smenton, Abby
    Tria, Scott
    Schrader, Thomas O.
    Jung, Jae-Kyu
    Esser, Craig
    Holt, Tom G.
    Wolff, Michael S.
    Taggart, Andrew K. P.
    Cheng, Kang
    Carballo-Jane, Ester
    Waters, M. Gerard
    Tata, James R.
    Colletti, Steven L.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (15) : 4472 - 4474
  • [5] GPR109a agonists. Part 1: 5-Alkyl and 5-aryl-pyrazole-tetrazoles as agonists of the human orphan G-protein coupled receptor GPR109a
    Imbriglio, Jason E.
    Chang, Sookhee
    Liang, Rui
    Raghavan, Subharekha
    Schmidt, Darby
    Smenton, Abby
    Tria, Scott
    Schrader, Thomas O.
    Jung, Jae-Kyu
    Esser, Craig
    Taggart, Andrew K. P.
    Cheng, Kang
    Carballo-Jane, Ester
    Waters, M. Gerard
    Tata, James R.
    Colletti, Steven L.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (08) : 2121 - 2124
  • [6] High-Affinity Niacin Receptor GPR109A Agonists
    Shen, Hong C.
    Colletti, Steven L.
    ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 45, 2010, 45 : 73 - +
  • [7] Future of GPR109A agonists in the treatment of dyslipidaemia
    Wanders, D.
    Judd, R. L.
    DIABETES OBESITY & METABOLISM, 2011, 13 (08) : 685 - 691
  • [8] Discovery of pyrazolyl propionyl cyclohexenamide derivatives as full agonists for the high affinity niacin receptor GPR109A
    Ding, Fa-Xiang
    Shen, Hong C.
    Wilsie, Larrisa C.
    Krsmanovic, Mihajlo L.
    Taggart, Andrew K.
    Ren, Ning
    Cai, Tian-Quan
    Wang, Junying
    Tong, Xinchun
    Holt, Tom G.
    Chen, Qing
    Waters, M. Gerard
    Hammond, Milton L.
    Tata, James R.
    Colletti, Steven L.
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (11) : 3372 - 3375
  • [9] Discovery of 4-(phenyl)thio-1H-pyrazole derivatives as agonists of GPR109A, a high affinity niacin receptor
    Kim, Hyeon Young
    Jadhav, Vithal B.
    Jeong, Dae Young
    Park, Woo Kyu
    Song, Jong-Hwan
    Lee, Sunkyung
    Cho, Heeyeong
    ARCHIVES OF PHARMACAL RESEARCH, 2015, 38 (06) : 1019 - 1032
  • [10] Nicotinic Acid Receptor GPR109A Is Down-Regulated in Human Macrophage-Derived Foam Cells
    Chai, Joshua T.
    Digby, Janet E.
    Ruparelia, Neil
    Jefferson, Andrew
    Handa, Ashok
    Choudhury, Robin P.
    PLOS ONE, 2013, 8 (05):
12345