Potent 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists: effects of fused heterocycles on antiviral activity and pharmacokinetic properties

被引：148
作者：
Kim, D
Wang, LP
Hale, JJ
Lynch, CL
Budhu, RJ
MacCross, M
Mills, SG
Malkowitz, L
Gould, SL
DeMartino, JA
Springer, MS
Hazuda, D
Miller, M
Kessler, J
Hrin, RC
Carver, G
Carella, A
Henry, K
Lineberger, J
Schleif, WA
Emini, EA
机构：
[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA
[2] Merck Res Labs, Dept Immunol Res, Rahway, NJ 07065 USA
[3] Merck Res Labs, Dept Antiviral Res, West Point, PA 19486 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 08期
关键词：
CCR5; HIV-1; antiviral; fused heterocycles;
D O I：
10.1016/j.bmcl.2005.02.030
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists containing a variety of fused heterocycles at the 4-position of the piperidine side chain has been discovered, which are orally bioavailable with potent anti-HIV activity. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码：2129 / 2134
页数：6
相关论文
共 28 条
  • [1] Chemokine receptors and chemokines in HIV infection
    Garzino-Demo, A
    Devico, AL
    Gallo, RC
    [J]. JOURNAL OF CLINICAL IMMUNOLOGY, 1998, 18 (04) : 243 - 255
  • [2] 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 3: Polar functionality and its effect on anti-HIV-1 activity
    Hale, JJ
    Budhu, RJ
    Mills, SG
    MacCoss, M
    Gould, SL
    DeMartino, JA
    Springer, MS
    Siciliano, SJ
    Malkowitz, L
    Schleif, WA
    Hazuda, D
    Miller, M
    Kessler, J
    Danzeisen, R
    Holmes, K
    Lineberger, J
    Carella, A
    Carver, G
    Emini, EA
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (20) : 2997 - 3000
  • [3] 1,3,4-trisubstituted pyrrolidine CCR5 receptor antagonists. Part 2: Lead optimization affording selective, orally bioavailable compounds with potent anti-HIV activity
    Hale, JJ
    Budhu, RJ
    Holson, EB
    Finke, PE
    Oates, B
    Mills, SG
    MacCoss, M
    Gould, SL
    DeMartino, JA
    Springer, MS
    Siciliano, S
    Malkowitz, L
    Schleif, WA
    Hazuda, D
    Miller, M
    Kessler, J
    Danzeisen, R
    Holmes, K
    Lineberger, J
    Carella, A
    Carver, G
    Emini, E
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (20) : 2741 - 2745
  • [4] 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 1: Discovery of the pyrrolidine scaffold and determination of its stereochemical requirements
    Hale, JJ
    Budhu, RJ
    Mills, SG
    MacCoss, M
    Malkowitz, L
    Siciliano, S
    Gould, SL
    DeMartino, JA
    Springer, MS
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (11) : 1437 - 1440
  • [5] Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells
    Hazuda, DJ
    Felock, P
    Witmer, M
    Wolfe, A
    Stillmock, K
    Grobler, JA
    Espeseth, A
    Gabryelski, L
    Schleif, W
    Blau, C
    Miller, MD
    [J]. SCIENCE, 2000, 287 (5453) : 646 - 650
  • [6] Horuk R, 2000, MED RES REV, V20, P155, DOI 10.1002/(SICI)1098-1128(200003)20:2<155::AID-MED3>3.0.CO
  • [7] 2-G
  • [8] HUNT SW, 1998, ANNU REP MED CHEM, V33, P263
  • [9] Recent progress in discovery of small-molecule CCR5 chemokine receptor ligands as HIV-1 inhibitors
    Kazmierski, W
    Bifulco, N
    Yang, HB
    Boone, L
    DeAnda, F
    Watson, C
    Kenakin, T
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY, 2003, 11 (13) : 2663 - 2676
  • [10] FACILE, REGIOSELECTIVE SYNTHESES OF N-ALKYLATED 2,3-DIAMINOPYRIDINES AND IMIDAZO[4,5-B]PYRIDINES
    KHANNA, IK
    WEIER, RM
    LENTZ, KT
    SWENTON, L
    LANKIN, DC
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (04) : 960 - 965
123