学术探索
学术期刊
新闻热点
数据分析
智能评审

1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 4: Synthesis of N-1 acidic functionality affording analogues with enhanced antiviral activity against HIV

被引：39
作者：
Lynch, CL
Hale, JJ
Budhu, RJ
Gentry, AL
Mills, SG
Chapman, KT
MacCoss, M
Malkowitz, L
Springer, MS
Gould, SL
DeMartino, JA
Siciliano, SJ
Cascieri, MA
Carella, A
Carver, G
Holmes, K
Schleif, WA
Danzeisen, R
Hazuda, D
Kessler, J
Lineberger, J
Miller, M
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, W Point, PA 19486 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 20期
关键词：
D O I：
10.1016/S0960-894X(02)00606-6
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of alpha-(pyrrolidin-1-yl)acetic acids is presented as selective and potent antivirals against HIV. Several of the pyrrolidine zwitterions demonstrated reasonable in vitro properties, enhanced antiviral activities and improved pharmacokinetic profiles over pyrrolidine 1. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：3001 / 3004
页数：4
相关论文
共 17 条
  • [1] Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures
    AbdelMagid, AF
    Carson, KG
    Harris, BD
    Maryanoff, CA
    Shah, RD
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (11) : 3849 - 3862
  • [2] 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
  • [3] SELECTIVE REDUCTIONS .37. ASYMMETRIC REDUCTION OF PROCHIRAL KETONES WITH B-(3-PINANYL)-9-BORABICYCLO[3.3.1]NONANE
    BROWN, HC
    PAI, GG
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1985, 50 (09) : 1384 - 1394
  • [4] ASYMMETRIC OXIDATION OF ESTER AND AMIDE ENOLATES USING NEW (CAMPHORYLSULFONYL)OXAZIRIDINES
    DAVIS, FA
    HAQUE, MS
    ULATOWSKI, TG
    TOWSON, JC
    [J]. JOURNAL OF ORGANIC CHEMISTRY, 1986, 51 (12) : 2402 - 2404
  • [5] AN EFFICIENT SYNTHESIS OF N-HYDROXY-ALPHA-AMINO ACID-DERIVATIVES OF HIGH OPTICAL PURITY
    FEENSTRA, RW
    STOKKINGREEF, EHM
    NIVARD, RJF
    OTTENHEIJM, HCJ
    [J]. TETRAHEDRON LETTERS, 1987, 28 (11) : 1215 - 1218
  • [6] Antagonists of the human CCR5 receptor as anti-HIV-1 agents.: Part 4:: Synthesis and structure-activity relationships for 1-[N(methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-(4-(N-(alkyl)-N- (benzyloxycarbonyl)amino)piperidin-1-yl)butanes
    Finke, PE
    Oates, B
    Mills, SG
    MacCoss, M
    Malkowitz, L
    Springer, MS
    Gould, SL
    DeMartino, JA
    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 (18) : 2475 - 2479
  • [7] 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
  • [8] 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
  • [9] 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
  • [10] 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
12