3-Amino-1-alkyl-cyclopentane carboxamides as small molecule antagonists of the human and murine CC chemokine receptor 2

被引:30
作者
Butora, Gabor [1 ]
Jiao, Richard [1 ]
Parsons, William H. [1 ]
Vicario, Pasquale P. [1 ]
Jin, Hong [1 ]
Ayala, Julia M. [1 ]
Cascieri, Margaret A. [1 ]
Yang, Lihu [1 ]
机构
[1] Merck Res Labs, Rahway, NJ 07065 USA
关键词
D O I
10.1016/j.bmcl.2007.04.053
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of low molecular weight antagonists of both the human and murine CC chemokine receptor 2, containing a l-alkyl-3-(3-methyl-4-spiroindenylpiperidine)-substituted cyclopentanecarboxamide, is described. A SAR study of the C, substituent revealed that short, branched alkyl groups such as isopropyl, isobutyl, or cyclopropyl are optimal for both human and murine CCR2 binding activity. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3636 / 3641
页数:6
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共 30 条
  • [21] Discovery of novel, potent, and selective small-molecule CCR5 antagonists as anti-HIV-1 agents: Synthesis and biological evaluation of anilide derivatives with a quaternary ammonium moiety
    Shiraishi, M
    Aramaki, Y
    Seto, M
    Imoto, H
    Nishikawa, Y
    Kanzaki, N
    Okamoto, M
    Sawada, H
    Nishimura, O
    Baba, M
    Fujino, M
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (10) : 2049 - 2063
  • [22] MCP-1 and CCR2 in HIV infection: Regulation of agonist and receptor expression
    Sozzani, S
    Introna, M
    Bernasconi, S
    Polentarutti, N
    Cinque, P
    Poli, G
    Sica, A
    Mantovani, A
    [J]. JOURNAL OF LEUKOCYTE BIOLOGY, 1997, 62 (01) : 30 - 33
  • [23] STETTER H, 1979, LIEBIGS ANN CHEM, P944
  • [24] Asymmetric synthesis and structure-activity relationship of the four stereoisomers of the antibiotic amidinomycin .1. The synthesis
    Sung, SY
    Frahm, AW
    [J]. ARCHIV DER PHARMAZIE, 1996, 329 (06) : 291 - 300
  • [25] Dancing to the tune of chemokines
    Thelen, M
    [J]. NATURE IMMUNOLOGY, 2001, 2 (02) : 129 - 134
  • [26] PALLADIUM-MEDIATED CYCLOADDITION APPROACH TO CYCLOPENTANOIDS - MECHANISTIC STUDIES
    TROST, BM
    CHAN, DMT
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1983, 105 (08) : 2326 - 2335
  • [27] PALLADIUM-MEDIATED CYCLOADDITION APPROACH TO CYCLOPENTANOIDS - INTRODUCTION AND INITIAL STUDIES
    TROST, BM
    CHAN, DMT
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1983, 105 (08) : 2315 - 2325
  • [28] Conformationally restricted indolopiperidine derivatives as potent CCR2B receptor antagonists
    Witherington, J
    Bordas, V
    Cooper, DG
    Forbes, IT
    Gribble, AD
    Ife, RJ
    Berkhout, T
    Gohil, J
    Groot, PHE
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (16) : 2177 - 2180
  • [29] YANG L, 2006, 232 FALL NAT M EXP S
  • [30] Discovery of 3,5-bis(trifluoromethyl)benzyl L-arylglycinamide based potent CCR2 antagonists
    Yang, LH
    Zhou, CY
    Guo, LQ
    Morriello, G
    Butora, G
    Pasternak, A
    Parsons, WH
    Mills, SG
    MacCoss, M
    Vicario, PP
    Zweerink, H
    Ayala, JM
    Goyal, S
    Hanlon, WA
    Cascieri, MA
    Springer, MS
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (14) : 3735 - 3739