1-(4-Chlorbenzyl)-5-methoxyisatin | 21728-29-0

• 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: 1-(4-Chlorbenzyl)-5-methoxyisatin
• 英文别名: 1-(4-chlorobenzyl)-5-methoxy-1H-indole-2,3-dione；1-[(4-chlorophenyl)methyl]-5-methoxyindole-2,3-dione
• CAS: 21728-29-0
• 化学式: C₁₆H₁₂ClNO₃
• 分子量: 301.729
• InChiKey: UOYXUOPRUDSKEA-UHFFFAOYSA-N

物化性质

• 沸点：
  489.0±55.0 °C(Predicted)
• 密度：
  1.391±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-Chlorbenzyl)-5-methoxyisatin 在 三溴化硼 、 水 、 sodium acetate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  鉴定并进一步开发与吲哚-2-酮螺合的噻唑烷酮类作为结核分枝杆菌蛋白酪氨酸磷酸酶B的有效和选择性抑制剂

  摘要：

  结核病仍然是全世界发病率和死亡率的主要原因。从蛋白酪氨酸磷酸酶结核分枝杆菌是由于它们在细胞内生存发展的作用在对抗结核病的新策略有吸引力的目标结核分枝杆菌的各种感染模型。在这里，我们报道了与吲哚啉酮-2螺环稠合的噻唑烷酮类化合物的鉴定和进一步开发，这是一类新型的结核分枝杆菌蛋白酪氨酸磷酸酶B的有效和选择性抑制剂。详细的结构-活性关系（SAR）研究表明：硝基取代的2-氧吲哚核与二卤代苯胺和卤代N-苄基部分对于针对MptpB（结核分枝杆菌蛋白酪氨酸磷酸酶B）的强抑制活性是必不可少的。所鉴定化合物的小结构修饰导致化合物溶解度和细胞渗透性的显着改善，从而在微摩尔范围内保持抑制活性。发现螺中心的构型对于抑制活性是至关重要的，并且外消旋物的分离显示出R -（-）-对映异构体是生物活性成分。报道的MptpB抑制剂对选定的一组蛋白酪氨酸磷酸酶（包括MptpA（结核分枝杆菌）蛋白酪氨酸磷酸酶A），PTP1B（

  DOI：

  10.1016/j.tet.2011.04.026
• 作为产物：
  描述：

  甲氧苯胺 在 盐酸 、 盐酸羟胺 、 sodium hydride 、 sodium sulfate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 12.5h， 生成 1-(4-Chlorbenzyl)-5-methoxyisatin
  参考文献：
  名称：

  Synthesis and evaluation of 3-ylideneoxindole acetamides as potent anticancer agents

  摘要：

  Indirubin, an active component in the traditional Chinese medicine formula Danggui Longhui Wan, shows promising anticancer effects. Meisoindigo is an analog derived from indirubin, which is less toxic and appears to be even more potent against cancer. In considering meisoindigo as a structural template for the development of new drugs, we designed and synthesized a series of 3-ylideneoxindole acetamides as novel anticancer agents. The acetamides were then evaluated for in vitro and in vivo anticancer activities. The 3-ylideneoxindole acetamides were found to have better anticancer activity than was indirubin-3'-oxime in several cancer cell lines and also displayed a spectrum of activity similar to that of the drug candidate roscovitine, a CDK inhibitor. Among the 3-ylideneoxindole acetamides, compound 10 showed particularly good efficacy. Cell cycle analysis further revealed that compound 10 arrested cells in the G1 phase and caused an increase in the sub-G1 population, indicating that the apoptosis pathway had been induced. In addition, exposure of cells to compound 10 led to the upregulation of the cell-cycle regulator cyclin D1, which was sustained at a high level. In contrast, the same compound induced a short-term elevation in the level of cyclin E, which was followed by a rapid decrease and the attenuation of Rb phosphorylation. Furthermore, a docking model suggests that compound 10 binds to the active site of CDK4. In testing the therapeutic potency of compound 10 on CT26-xenografted BALB/c mice, a significant reduction in tumor size comparable to that of cisplatin was found when administrated via the i.p. route. The mice presented no loss of body weight, indicating that this compound possesses low toxicity. In the future, we are planning in vivo investigations of these new active anticancer agents to better elucidate active mechanisms at the cellular level and thus benefit the development of anticancer therapies. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.062

文献信息

• NHC-Catalyzed Aldol-Like Reactions of Allenoates with Isatins: Regiospecific Syntheses of γ-Functionalized Allenoates
  作者：Sha Li、Ziwei Tang、Yang Wang、Dan Wang、Zhanlin Wang、Chenxia Yu、Tuanjie Li、Donghui Wei、Changsheng Yao

  DOI：10.1021/acs.orglett.8b04082

  日期：2019.3.1

  carbene (NHC) catalyzed γ-specific aldol-like reaction between allenoates and isatins has been achieved under mild conditions, giving trisubstituted allene derivatives bearing isatin moiety in moderate to good yields with high diastereoselectivity and excellent atom efficiency. The DFT computations indicated that the formation of the γ-adduct was more energetically favorable than that of the α-adduct. The

  在温和的条件下已实现了N-杂环卡宾（NHC）催化的烯丙酸酯和异戊二烯之间的γ-特异性羟醛类似的反应，从而以中等至良好的收率得到了具有异丁烯部分的三取代的烯丙二烯衍生物，具有高的非对映选择性和出色的原子效率。DFT计算表明，与α-加合物相比，γ-加合物的形成在能量上更有利。本文报道的结果为NHC促进的涉及烯丙酸酯的反应开辟了一条新途径。
• Design, synthesis, docking studies and anticancer evaluation of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole] derivatives on MIN-6 cancer cell line
  作者：Pradeep Patil、Nippu B． N．、N． D． Satyanarayan、Santosh Pore、Rutuja Zond、Akshay Gurav、Shankar Hangirgekar、Sandeep Sankpal

  DOI：10.1016/j.molstruc.2022.134772

  日期：2023.4

  A series of spiro[indoline-3,4′-pyrano[2,3-c]pyrazoles] were synthesized by a one-pot four-component reaction of ethyl acetoacetate, hydrazine hydrate, malononitrile, and isatin catalyzed by new polymer-supported ionic liquid (PSIL) catalyst in an aqueous solution at ambient conditions. Newly synthesized compounds were fully characterized by FT-IR, 1H and 13C NMR, and mass spectrometry. The pharmacokinetic

  以乙酰乙酸乙酯、水合肼、丙二腈和靛红为载体的新型聚合物催化一锅四元反应合成了一系列螺[二氢吲哚-3,4'-吡喃并[2,3-c]吡唑]在环境条件下水溶液中的离子液体 (PSIL) 催化剂。新合成的化合物通过 FT-IR、1 H 和13 C NMR 以及质谱法进行了全面表征。筛选药代动力学特性，然后在 COX-2 上进行分子对接以检查计算机效能。针对 Min-6 胰腺癌细胞系评估了5a-j分子的细胞毒性。5a -j已发现分子具有良好的药物特性和与 COX-2 酶的良好结合亲和力。此外，合成化合物的体外细胞毒性潜力显示出对癌细胞系有希望的抑制潜力。与其他类似物相比，最有前途的化合物5e (IC 50 11.33)和5g (IC 50 17.30)显示出最显着的细胞毒活性。结果表明，设计的分子是用于升级生物学评估的有前途的产品。
• Identification and further development of thiazolidinones spiro-fused to indolin-2-ones as potent and selective inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B
  作者：Viktor V. Vintonyak、Karin Warburg、Björn Over、Katja Hübel、Daniel Rauh、Herbert Waldmann

  DOI：10.1016/j.tet.2011.04.026

  日期：2011.9

  biologically active component. The reported MptpB inhibitors show excellent selectivity against a selected panel of protein tyrosine phosphatases, including MptpA (M. tuberculosis protein tyrosine phosphatase A), PTP1B (protein tyrosine phosphatase 1B), SHP-2 (Src homology 2 domain-containing protein tyrosine phosphatase), PTPN2, h-PTPβ (human protein tyrosine phosphatase β), and VHR (Vaccinia virus VH1-related

  结核病仍然是全世界发病率和死亡率的主要原因。从蛋白酪氨酸磷酸酶结核分枝杆菌是由于它们在细胞内生存发展的作用在对抗结核病的新策略有吸引力的目标结核分枝杆菌的各种感染模型。在这里，我们报道了与吲哚啉酮-2螺环稠合的噻唑烷酮类化合物的鉴定和进一步开发，这是一类新型的结核分枝杆菌蛋白酪氨酸磷酸酶B的有效和选择性抑制剂。详细的结构-活性关系（SAR）研究表明：硝基取代的2-氧吲哚核与二卤代苯胺和卤代N-苄基部分对于针对MptpB（结核分枝杆菌蛋白酪氨酸磷酸酶B）的强抑制活性是必不可少的。所鉴定化合物的小结构修饰导致化合物溶解度和细胞渗透性的显着改善，从而在微摩尔范围内保持抑制活性。发现螺中心的构型对于抑制活性是至关重要的，并且外消旋物的分离显示出R -（-）-对映异构体是生物活性成分。报道的MptpB抑制剂对选定的一组蛋白酪氨酸磷酸酶（包括MptpA（结核分枝杆菌）蛋白酪氨酸磷酸酶A），PTP1B（
• Synthesis and evaluation of 3-ylideneoxindole acetamides as potent anticancer agents
  作者：Chun-Tang Chiou、Wei-Chun Lee、Jiahn-Haur Liao、Jing-Jy Cheng、Lie-Chwen Lin、Chih-Yu Chen、Jen-Shin Song、Ming-Hsien Wu、Kak-Shan Shia、Wen-Tai Li

  DOI：10.1016/j.ejmech.2015.04.062

  日期：2015.6

  Indirubin, an active component in the traditional Chinese medicine formula Danggui Longhui Wan, shows promising anticancer effects. Meisoindigo is an analog derived from indirubin, which is less toxic and appears to be even more potent against cancer. In considering meisoindigo as a structural template for the development of new drugs, we designed and synthesized a series of 3-ylideneoxindole acetamides as novel anticancer agents. The acetamides were then evaluated for in vitro and in vivo anticancer activities. The 3-ylideneoxindole acetamides were found to have better anticancer activity than was indirubin-3'-oxime in several cancer cell lines and also displayed a spectrum of activity similar to that of the drug candidate roscovitine, a CDK inhibitor. Among the 3-ylideneoxindole acetamides, compound 10 showed particularly good efficacy. Cell cycle analysis further revealed that compound 10 arrested cells in the G1 phase and caused an increase in the sub-G1 population, indicating that the apoptosis pathway had been induced. In addition, exposure of cells to compound 10 led to the upregulation of the cell-cycle regulator cyclin D1, which was sustained at a high level. In contrast, the same compound induced a short-term elevation in the level of cyclin E, which was followed by a rapid decrease and the attenuation of Rb phosphorylation. Furthermore, a docking model suggests that compound 10 binds to the active site of CDK4. In testing the therapeutic potency of compound 10 on CT26-xenografted BALB/c mice, a significant reduction in tumor size comparable to that of cisplatin was found when administrated via the i.p. route. The mice presented no loss of body weight, indicating that this compound possesses low toxicity. In the future, we are planning in vivo investigations of these new active anticancer agents to better elucidate active mechanisms at the cellular level and thus benefit the development of anticancer therapies. (C) 2015 Elsevier Masson SAS. All rights reserved.