CCR5 antagonists: 3-(pyrrolidin-1-yl)propionic acid analogues with potent anti-HIV activity

被引：17
|
作者：
Lynch, CL
Hale, JJ
Budhu, RJ
Gentry, AL
Finke, PE
Caldwell, CG
Mills, SG
MacCoss, M
Shen, DM
Chapman, KT
Malkowitz, L
Springer, MS
Gould, SL
DeMartino, JA
Siciliano, SJ
Cascieri, MA
Carella, A
Carver, G
Karen, H
Schleif, WA
Danzeisen, R
Hazuda, D
Kessler, J
Lineberger, J
Miller, M
Emini, E
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：
ORGANIC LETTERS | 2003年 / 5卷 / 14期
关键词：
D O I：
10.1021/ol034707c
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
graphic A novel approach to alpha,alpha-disubstituted-beta-amino acids (beta(2,2)-amino acids) was employed in the synthesis of a series of 3-(pyrrolidin-1-yl)-propionic acids possessing high affinity for the CCR5 receptor and potent anti-HIV activity. The rat pharmacokinetics for these new analogues featured higher bioavailabilities and lower rates of clearance as compared to cyclopentane 1.
引用
收藏
页码：2473 / 2475
页数：3
相关论文
共 50 条
  • [1] Synthesis of benzocycloheptene derivatives as CCR5 antagonists with potent anti-HIV activity
    Liu, Yao
    Su, Jing
    Xiao, Jun Hai
    Jiang, Shi Bo
    Lu, Hong
    Zhong, Wu
    Wang, Li Li
    Yang, Xiao Hong
    Li, Song
    CHINESE CHEMICAL LETTERS, 2008, 19 (04) : 428 - 430
  • [2] Synthesis of benzocycloheptene derivatives as CCR5 antagonists with potent anti-HIV activity
    Yao Liu~(a
    ChineseChemicalLetters, 2008, (04) : 428 - 430
  • [3] CCR5 antagonists as anti-HIV agents
    不详
    DRUG DISCOVERY TODAY, 2001, 6 (14) : 747 - 747
  • [4] CCR5 antagonists as anti-HIV agents
    Lloyd, AW
    DRUG DISCOVERY TODAY, 2000, 5 (09) : 428 - 429
  • [5] CCR5 antagonists with anti-HIV activity: Is inhibition on the cell surface sufficient?
    Springer, M
    BRITISH JOURNAL OF PHARMACOLOGY, 2002, 135
  • [6] Molecular interactions of CCR5 with major classes of small-molecule anti-HIV CCR5 antagonists
    Kondru, Rama
    Zhang, Jun
    Ji, Changhua
    Mirzadegan, Tara
    Rotstein, David
    Sankuratri, Surya
    Dioszegi, Marianna
    MOLECULAR PHARMACOLOGY, 2008, 73 (03) : 789 - 800
  • [7] Rapamycin enhances aplaviroc anti-HIV activity: Implications for the clinical development of novel CCR5 antagonists
    Latinovic, Olga
    Heredia, Alonso
    Gallo, Robert C.
    Reitz, Marv
    Le, Nhut
    Redfield, Robert R.
    ANTIVIRAL RESEARCH, 2009, 83 (01) : 86 - 89
  • [8] Analyses of Anti-HIV Type 1 Activity of a Small CCR5 Peptide Antagonist
    Wang, Fang Yu
    He, Shu Ya
    Zhang, Zhi Jian
    He, Li Fang
    Chen, Xiao Wei
    Teng, Tao
    AIDS RESEARCH AND HUMAN RETROVIRUSES, 2011, 27 (10) : 1111 - 1115
  • [9] QSAR analyses of 3-(4-benzylpiperidin-1-yl)-N-phenylpropylamine derivatives as potent CCR5 antagonists
    Roy, K
    Leonard, JT
    JOURNAL OF CHEMICAL INFORMATION AND MODELING, 2005, 45 (05) : 1352 - 1368
  • [10] Novel CCR5 monoclonal antibodies with potent and broad-spectrum anti-HIV activities
    Ji, Changhua
    Brandt, Michael
    Dioszegi, Marianna
    Jekle, Andreas
    Schwoerer, Stephan
    Challand, Steven
    Zhang, Jun
    Chen, Yun
    Zautke, Lisa
    Achhammer, Gunthar
    Baehner, Monika
    Kroetz, Sandra
    Heilek-Snyder, Gabrielle
    Schumacher, Ralf
    Cammack, Nick
    Sankuratri, Surya
    ANTIVIRAL RESEARCH, 2007, 74 (02) : 125 - 137
12345