Synthesis and Evaluation of Indole Aspartyl Ketones as Novel Caspase-3 Inhibitors

被引：0
|
作者：
Sengupta, S. [1 ]
Rao, G. Venkateshwar [1 ]
Dubey, P. K. [2 ]
机构：
[1] Aurigene Discovery Technol Ltd, Div Med Chem, Bangalore 560100, Karnataka, India
[2] Jawaharlal Nehru Technol Univ, Coll Engn, Dept Chem, Hyderabad 500085, Andhra Pradesh, India
来源：
ASIAN JOURNAL OF CHEMISTRY | 2011年 / 23卷 / 12期
关键词：
Caspase inhibitors; Cysteine proteases; IDN-6556; Indole-N-acetic acid; IN-VIVO; POTENT; FLUOROMETHYLKETONES; APOPTOSIS; INTERLEUKIN-1-BETA; ACTIVATION; DIPEPTIDES; DISCOVERY; SAR;
D O I：
暂无
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Synthesis, biological evaluation and structure-activity relationships for a series of novel nonpeptide small molecule inhibitors of caspase-3 are described. Among the synthesized compounds, 2,3,5,6-tetrafluorophenoxymethyl ketone derivatives of indole-N-acetamides have been identified as potent inhibitors of caspase-3. The most active compound within this series (9a) inhibited caspase-3 with an IC50 = 0.64 mu M.
引用
收藏
页码：5517 / 5520
页数：4
相关论文
共 50 条
  • [1] Nicotinyl aspartyl ketones as inhibitors of caspase-3
    Isabel, E
    Black, WC
    Bayly, CI
    Grimm, EL
    Janes, MK
    McKay, DJ
    Nicholson, DW
    Rasper, DM
    Renaud, J
    Roy, S
    Tam, J
    Thornberry, NA
    Vaillancourt, JP
    Xanthoudakis, S
    Zamboni, R
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (13) : 2137 - 2140
  • [2] Discovery of novel aspartyl ketone dipeptides as potent and selective caspase-3 inhibitors
    Giroux, A
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2005, 230 : U3315 - U3315
  • [3] Synthesis and biological evaluation of novel oxalamido derivatives as caspase-3 inhibitors
    Sengupta, Saumitra
    Rao, G. Venkateshwar
    Dubey, P. K.
    INDIAN JOURNAL OF CHEMISTRY SECTION B-ORGANIC CHEMISTRY INCLUDING MEDICINAL CHEMISTRY, 2011, 50 (07): : 901 - 905
  • [4] Discovery of novel aspartyl ketone dipeptides as potent and selective caspase-3 inhibitors
    Han, YX
    Giroux, A
    Grimm, EL
    Aspiotis, R
    Francoeur, S
    Bayly, CI
    Mckay, DJ
    Roy, S
    Xanthoudakis, S
    Vaillancourt, JP
    Rasper, DM
    Tam, J
    Tawa, P
    Thornberry, NA
    Paterson, EP
    Garcia-Calvo, M
    Becker, JW
    Rotonda, J
    Nicholson, DW
    Zamboni, RJ
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (03) : 805 - 808
  • [5] Synthesis and evaluation of novel dipeptidyl benzoyloxymethyl ketones as caspase inhibitors
    Nedev, HN
    Klaiman, G
    LeBlanc, A
    Saragovi, HU
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 336 (02) : 397 - 400
  • [6] Design and synthesis of new nonpeptide caspase-3 inhibitors
    Kravchenko D.V.
    Ivanenkov Ya.A.
    Balakin K.V.
    Kisil V.M.
    Tkachenko S.E.
    Okun' I.M.
    Ivashchenko A.V.
    Pharmaceutical Chemistry Journal, 2006, 40 (3) : 127 - 131
  • [7] Solid phase synthesis of caspase-3 inhibitors.
    Grimm, EL
    Aspiotis, R
    Bayly, C
    Garcia-Calvo, M
    Giroux, A
    Han, YX
    McKay, D
    Nicholson, D
    Peterson, E
    Rasper, D
    Renaud, J
    Roy, S
    Tam, J
    Tawa, P
    Thornberry, N
    Vaillancourt, J
    Zamboni, R
    Xanthoudakis, S
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2000, 220 : U583 - U583
  • [8] Synthesis and evaluation of novel prodrugs of caspase inhibitors
    Charrier, Jean-Damien
    Durrant, Steven J.
    Studley, John
    Lawes, Linda
    Weber, Peter
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (01) : 485 - 488
  • [9] Solid phase synthesis of selective caspase-3 peptide inhibitors
    Grimm, EL
    Roy, B
    Aspiotis, R
    Bayly, CI
    Nicholson, DW
    Rasper, DM
    Renaud, J
    Roy, S
    Tam, J
    Tawa, P
    Vaillancourt, JP
    Xanthoudakis, S
    Zamboni, RJ
    BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (05) : 845 - 851
  • [10] SYNTHESIS OF NOVEL DIPEPTIDYL ROYLOXY- METHYL KETONES AS CASPASE INHIBITORS
    Nedev, H.
    Saragovi, H. U.
    BIOPOLYMERS, 2011, 96 (04) : 485 - 485
12345