4-(2-(Indolin-1-yl)-2-oxoethoxy)-3-methoxybenzaldehyde

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-(2-(Indolin-1-yl)-2-oxoethoxy)-3-methoxybenzaldehyde
• 英文别名: 4-[2-(2,3-dihydroindol-1-yl)-2-oxoethoxy]-3-methoxybenzaldehyde
• 化学式: C₁₈H₁₇NO₄
• mdl: MFCD05239413
• 分子量: 311.337
• InChiKey: BHTRUPXMSDDFEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-吲哚酮 、 4-(2-(Indolin-1-yl)-2-oxoethoxy)-3-methoxybenzaldehyde 在 哌啶 作用下， 以 乙醇 为溶剂， 以89%的产率得到(Z)-3-(4'-(2-(indolin-1-yl)-2-oxoethoxy)-3'-methoxybenzylidene)indolin-2-one
  参考文献：
  名称：

  Design, synthesis and apoptosis inducing effect of novel (Z)-3-(3′-methoxy-4′-(2-amino-2-oxoethoxy)-benzylidene)indolin-2-ones as potential antitumour agents

  摘要：

  A series of new (Z)-3-(3'-methoxy-4'-(2-amino-2-oxoethoxy)benzylidene)indolin-2-one derivatives has been synthesized and evaluated for their cytotoxic activity against selected human cancer cell lines of prostate (PC-3 and DU-145), breast (BT-549 and MDA-MB-231) and non-tumorigenic prostate epithelial cells (RWPE-1). Among the tested, one of the compounds 4p exhibited potent cytotoxicity selectively on prostate cancer cell lines (PC-3 and DU-145; IC50: 1.89 +/- 0.6 and 1.94 +/- 0.2 mu M, respectively). Further experiments were conducted with 4p on PC-3 cancer cells to study the mechanisms of growth inhibition and apoptosis inducing effect. Treatment of PC-3 cells with test compound 4p resulted in inhibition of cell migration through disorganization of F-actin protein. The flow-cytometry analysis results showed that the compound arrested PC-3 cancer cells in the G2/M phase of cell cycle in a dose dependent manner. Hoechst staining and annexin-V binding assay revealed that the compound 4p inhibited tumor cell proliferation through induction of apoptosis. Western blot studies demonstrated that the compound 4p treatment led to activation of caspase-3, increased, expression of pro-apoptotic Bax and significantly decreased expression of anti-apoptotic Bcl-2 in human prostate cancer PC-3 cells. In addition, the mitochondrial membrane potential (Delta Psi m) was also affected and the levels of intracellular Ca2+ were raised. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.025
• 作为产物：
  描述：

  吲哚啉 在 potassium carbonate 作用下， 以 neat liquid 为溶剂， 生成 4-(2-(Indolin-1-yl)-2-oxoethoxy)-3-methoxybenzaldehyde
  参考文献：
  名称：

  Design, synthesis and apoptosis inducing effect of novel (Z)-3-(3′-methoxy-4′-(2-amino-2-oxoethoxy)-benzylidene)indolin-2-ones as potential antitumour agents

  摘要：

  A series of new (Z)-3-(3'-methoxy-4'-(2-amino-2-oxoethoxy)benzylidene)indolin-2-one derivatives has been synthesized and evaluated for their cytotoxic activity against selected human cancer cell lines of prostate (PC-3 and DU-145), breast (BT-549 and MDA-MB-231) and non-tumorigenic prostate epithelial cells (RWPE-1). Among the tested, one of the compounds 4p exhibited potent cytotoxicity selectively on prostate cancer cell lines (PC-3 and DU-145; IC50: 1.89 +/- 0.6 and 1.94 +/- 0.2 mu M, respectively). Further experiments were conducted with 4p on PC-3 cancer cells to study the mechanisms of growth inhibition and apoptosis inducing effect. Treatment of PC-3 cells with test compound 4p resulted in inhibition of cell migration through disorganization of F-actin protein. The flow-cytometry analysis results showed that the compound arrested PC-3 cancer cells in the G2/M phase of cell cycle in a dose dependent manner. Hoechst staining and annexin-V binding assay revealed that the compound 4p inhibited tumor cell proliferation through induction of apoptosis. Western blot studies demonstrated that the compound 4p treatment led to activation of caspase-3, increased, expression of pro-apoptotic Bax and significantly decreased expression of anti-apoptotic Bcl-2 in human prostate cancer PC-3 cells. In addition, the mitochondrial membrane potential (Delta Psi m) was also affected and the levels of intracellular Ca2+ were raised. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.04.025

文献信息

• Chemical entities that kill senescent cells for use in treating age-related disease
  申请人：Unity Biotechnology, Inc.

  公开号：US10195213B2

  公开（公告）日：2019-02-05

  Disclosed herein are compounds that are effective for treatment of various disease states associated with senescence. The disclosed compounds can be used to eliminate senescent cells for disease treatment. The dosing of the compounds includes both single administration and regimens of cycling dosages.

  本文公开的化合物可有效治疗与衰老有关的各种疾病状态。所公开的化合物可用于消除衰老细胞以治疗疾病。化合物的给药方式包括单次给药和循环给药。
• CHEMICAL MODULATORS OF PRO-APOPTOTIC BAX AND BCL-2 POLYPEPTIDES
  申请人：Walensky Loren D.

  公开号：US20110218155A1

  公开（公告）日：2011-09-08

  The invention provides a method for identifying a compound which modulates the activity of a BCL-2 family polypeptide, the method comprising: a) contacting said BCL-2 family polypeptide with a compound under conditions suitable for modulation of the activity of said BCL-2 family polypeptide; and b) detecting modulation of the activity of said BCL-2 family polypeptide by the compound, wherein the compound interacts with a binding site comprising one or more of an α1 helix, α2 helix, a loop between α1-α2, α.6 helix, and select residues of α4, α.5, and α.8 helices in said BCL-2 family polypeptide; wherein the interaction of the compound with the binding site occurs at a horizontal hydrophobic groove with or without a perimeter of charged and hydrophilic residues, a superior juxta-loop, an inferior juxta-loop, or combination thereof.
• Chemical Modulators of Pro-Apoptotic BAX and BCL-2 Polypeptides
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US20160171150A1

  公开（公告）日：2016-06-16

  The invention provides a method for identifying a compound which modulates the activity of a BCL-2 family polypeptide, the method comprising: a) contacting said BCL-2 family polypeptide with a compound under conditions suitable for modulation of the activity of said BCL-2 filially polypeptide; and b) detecting modulation of the activity of said BCL-2 family polypeptide by the compound, wherein the compound interacts with a binding site comprising one or more of an α1 helix, α2 helix, a loop between α1-α2, α.6 helix, and select residues of α4, α.5, and α.8 helices in said BCL-2 family polypeptide; wherein the interaction of the compound with the binding site occurs at a horizontal hydrophobic groove with or without a perimeter of charged and hydrophilic residues, a superior juxta-loop, an inferior juxta-loop, or combination thereof.
• COMPOUNDS AND THERAPEUTIC USES
  申请人：Unity Biotechnology, Inc.

  公开号：US20170281649A1

  公开（公告）日：2017-10-05

  Disclosed herein are compounds that are effective for treatment of various disease states associated with senescence. The disclosed compounds can be used to eliminate senescent cells for disease treatment. The dosing of the compounds includes both single administration and regimens of cycling dosages.
• Design, synthesis and apoptosis inducing effect of novel (Z)-3-(3′-methoxy-4′-(2-amino-2-oxoethoxy)-benzylidene)indolin-2-ones as potential antitumour agents
  作者：Kishna Ram Senwar、T. Srinivasa Reddy、Dinesh Thummuri、Pankaj Sharma、V.G.M. Naidu、Gannoju Srinivasulu、Nagula Shankaraiah

  DOI：10.1016/j.ejmech.2016.04.025

  日期：2016.8

  A series of new (Z)-3-(3'-methoxy-4'-(2-amino-2-oxoethoxy)benzylidene)indolin-2-one derivatives has been synthesized and evaluated for their cytotoxic activity against selected human cancer cell lines of prostate (PC-3 and DU-145), breast (BT-549 and MDA-MB-231) and non-tumorigenic prostate epithelial cells (RWPE-1). Among the tested, one of the compounds 4p exhibited potent cytotoxicity selectively on prostate cancer cell lines (PC-3 and DU-145; IC50: 1.89 +/- 0.6 and 1.94 +/- 0.2 mu M, respectively). Further experiments were conducted with 4p on PC-3 cancer cells to study the mechanisms of growth inhibition and apoptosis inducing effect. Treatment of PC-3 cells with test compound 4p resulted in inhibition of cell migration through disorganization of F-actin protein. The flow-cytometry analysis results showed that the compound arrested PC-3 cancer cells in the G2/M phase of cell cycle in a dose dependent manner. Hoechst staining and annexin-V binding assay revealed that the compound 4p inhibited tumor cell proliferation through induction of apoptosis. Western blot studies demonstrated that the compound 4p treatment led to activation of caspase-3, increased, expression of pro-apoptotic Bax and significantly decreased expression of anti-apoptotic Bcl-2 in human prostate cancer PC-3 cells. In addition, the mitochondrial membrane potential (Delta Psi m) was also affected and the levels of intracellular Ca2+ were raised. (C) 2016 Elsevier Masson SAS. All rights reserved.