1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 1: Discovery of the pyrrolidine scaffold and determination of its stereochemical requirements

被引：55
作者：
Hale, JJ [1 ]
Budhu, RJ
Mills, SG
MacCoss, M
Malkowitz, L
Siciliano, S
Gould, SL
DeMartino, JA
Springer, MS
机构：
[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA
[2] Merck Res Labs, Dept Immunol Res, Rahway, NJ 07065 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 11期
关键词：
D O I：
10.1016/S0960-894X(01)00232-3
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 pyrrolidines was discovered to have the ability to displace [I-125]-MIP-1 alpha from the CCR5 receptor expressed on Chinese hamster ovary (CHO) cell membranes. CCR5 activity was found to be dependent on the regiochemistry and the absolute stereochemistry of the pyrrolidine. (C) 2001 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：1437 / 1440
页数：4
相关论文
共 24 条
  • [1] A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity
    Baba, M
    Nishimura, O
    Kanzaki, N
    Okamoto, M
    Sawada, H
    Iizawa, Y
    Shiraishi, M
    Aramaki, Y
    Okonogi, K
    Ogawa, Y
    Meguro, K
    Fujino, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (10) : 5698 - 5703
  • [2] Baroudy B. M., 2000, 7 C RETR OPP INF SAN
  • [3] *CDCP, 1999, HIV AIDS SURVEILLANC, V5, P1
  • [4] Free radical method for the synthesis of spiro-piperidinyl heterocycles
    Chen, MH
    Abraham, JA
    [J]. TETRAHEDRON LETTERS, 1996, 37 (30) : 5233 - 5234
  • [5] Synthesis and biological activities of spiroheterocyclic growth hormone secretagogues
    Chen, MH
    Pollard, PP
    Patchett, AA
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (09) : 1261 - 1266
  • [6] COOCHI F, 1995, SCIENCE, V270, P1811
  • [7] Identification of a major co-receptor for primary isolates of HIV-1
    Deng, HK
    Liu, R
    Ellmeier, W
    Choe, S
    Unutmaz, D
    Burkhart, M
    DiMarzio, P
    Marmon, S
    Sutton, RE
    Hill, CM
    Davis, CB
    Peiper, SC
    Schall, TJ
    Littman, DR
    Landau, NR
    [J]. NATURE, 1996, 381 (6584) : 661 - 666
  • [8] Use of a gp120 binding assay to dissect the requirements and kinetics of human immunodeficiency virus fusion events
    Doranz, BJ
    Baik, SSW
    Doms, RW
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (12) : 10346 - 10358
  • [9] Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 1: Discovery and initial structure-activity relationships for 1-amino-2-phenyl-4-(piperidin-1-yl)butanes
    Dorn, CP
    Finke, PE
    Oates, B
    Budhu, RJ
    Mills, SG
    MacCoss, M
    Malkowitz, L
    Springer, MS
    Daugherty, BL
    Gould, SL
    DeMartino, JA
    Siciliano, SJ
    Carella, A
    Carver, G
    Holmes, K
    Danzeisen, R
    Hazuda, D
    Kessler, J
    Lineberger, J
    Miller, M
    Schleif, WA
    Emini, EA
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (02) : 259 - 264
  • [10] HIV-1 entry into CD4(+) cells is mediated by the chemokine receptor CC-CKR-5
    Dragic, T
    Litwin, V
    Allaway, GP
    Martin, SR
    Huang, YX
    Nagashima, KA
    Cayanan, C
    Maddon, PJ
    Koup, RA
    Moore, JP
    Paxton, WA
    [J]. NATURE, 1996, 381 (6584) : 667 - 673
123