Hepatitis C virus NS3-4A serine protease inhibitors:: Use of a P2-P1 cyclopropyl alanine combination for improved potency

被引：23
作者：
Bogen, S
Saksena, AK
Arasappan, A
Gu, H
Njoroge, FG
Girijavallabhan, V
Pichardo, J
Butkiewicz, N
Prongay, A
Madison, V
机构：
[1] Schering Plough Corp, Res Inst, Chem Res, Kenilworth, NJ 07033 USA
[2] Schering Plough Corp, Res Inst, Antiviral Therapy, Kenilworth, NJ 07033 USA
[3] Schering Plough Corp, Res Inst, Struct Chem, Kenilworth, NJ 07033 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 20期
关键词：
Hepatatis C; P3 capped ketoamide; inhibitor;
D O I：
10.1016/j.bmcl.2005.07.009
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Modification of the P, and P, side chains of earlier P-3-capped alpha-kctoamide inhibitor of HCV NS3 serine protease 1 resulted in the discovery of compound 24 with about 10-fold improvement in potency. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4515 / 4519
页数：5
相关论文
共 32 条
  • [1] [Anonymous], 1999, J Hepatol, V30, P956
  • [2] Novel 2-oxoimidazolidine-4-carboxylic acid derivatives as Hepatitis C virus NS3-4A serine protease inhibitors: synthesis, activity, and X-ray crystal structure of an enzyme inhibitor complex
    Arasappan, A
    Njoroge, FG
    Parekh, TN
    Yang, XZ
    Pichardo, J
    Butkiewicz, N
    Prongay, A
    Yao, NH
    Girijavallabhan, V
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (23) : 5751 - 5755
  • [3] ARASAPPAN A, UNPUB BIOORG MED CHE
  • [4] The design and synthesis of potent inhibitors of hepatitis C virus NS3-4A proteinase
    Attwood, MR
    Bennett, JM
    Campbell, AD
    Canning, GGM
    Carr, MG
    Conway, E
    Dunsdon, RM
    Greening, JR
    Jones, PS
    Kay, PB
    Handa, BK
    Hurst, DN
    Jennings, NS
    Jordan, S
    Keech, E
    O'Brien, MA
    Overton, HH
    King-Underwood, J
    Raynham, TM
    Stenson, KP
    Wilkinson, CS
    Wilkinson, TCI
    Wilson, FX
    [J]. ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1999, 10 (05) : 259 - 273
  • [5] Replication of hepatitis C virus
    Bartenschlager, R
    Lohmann, V
    [J]. JOURNAL OF GENERAL VIROLOGY, 2000, 81 : 1631 - 1648
  • [6] The identification of α-ketoamides as potent inhibitors of hepatitis C virus NS3-4A proteinase
    Bennett, JM
    Campbell, AD
    Campbell, AJ
    Carr, MG
    Dunsdon, RM
    Greening, JR
    Hurst, DN
    Jennings, NS
    Jones, PS
    Jordan, S
    Kay, PB
    O'Brien, MA
    King-Underwood, J
    Raynham, TM
    Wilkinson, CS
    Wilkinson, TCI
    Wilson, FX
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2001, 11 (03) : 355 - 357
  • [7] The scientific challenge of hepatitis C
    Cohen, J
    [J]. SCIENCE, 1999, 285 (5424) : 26 - 30
  • [8] Phenethyl amides as novel noncovalent inhibitors of hepatitis C virus NS3/4A protease:: Discovery, initial SAR, and molecular modeling
    Colarusso, S
    Koch, U
    Gerlach, B
    Steinkühler, C
    De Francesco, R
    Altamura, S
    Matassa, VG
    Narjes, F
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (03) : 345 - 348
  • [9] HEPATITIS-C - PROGRESS AND PROBLEMS
    CUTHBERT, JA
    [J]. CLINICAL MICROBIOLOGY REVIEWS, 1994, 7 (04) : 505 - &
  • [10] Approaching a new era for hepatitis C virus therapy: inhibitors of the NS3-4A serine protease and the NS5B RNA-dependent RNA polymerase
    De Francesco, R
    Tomei, L
    Altamura, S
    Summa, V
    Migliaccio, G
    [J]. ANTIVIRAL RESEARCH, 2003, 58 (01) : 1 - 16
1234