1-(4-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indol-7-ylamine | 916484-09-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indol-7-ylamine
• 英文别名: 1-(4-methoxyphenyl)sulfonyl-2,3-dihydroindol-7-amine
• CAS: 916484-09-8
• 化学式: C₁₅H₁₆N₂O₃S
• 分子量: 304.37
• InChiKey: UADZURREYBYPFN-UHFFFAOYSA-N

物化性质

• 熔点：
  104-106 °C
• 沸点：
  500.6±60.0 °C(Predicted)
• 密度：
  1.364±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  81
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indol-7-ylamine 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三溴化硼 、 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 N-(2-aminophenyl)-4-(((1-((4-hydroxyphenyl)sulfonyl)indolin-7-yl)amino)methyl)benzamide
  参考文献：
  名称：

  1-芳磺酰基吲哚-苯甲酰胺类新药，具有抑制组蛋白脱乙酰基酶的作用

  摘要：

  我们报告基于1-芳基磺酰基吲哚的苯甲酰胺的结构活性关系。苯甲酰胺（9）表现出显着的微管蛋白抑制作用，IC 50值为1.1μM，优于康培他汀A-4（3），并且对多种癌细胞具有显着的抗增殖活性，包括具有IC的MDR阳性细胞系50值分别为49 nM（KB），79 nM（A549），63 nM（MKN45），64 nM（KB-VIN10），43 nM（KB-S15）和46 nM（KB-7D）。化合物的双重抑制潜力9被发现，因为它显示出在比较针对HDAC1，2和6显著抑制潜力到MS-275（6）。9的一些关键交互通过分子建模已经找出了具有微管蛋白活性位点的氨基酸残基和具有HDAC 1同工型的氨基酸残基的化合物。化合物9在人非小细胞肺癌A549异种移植模型以及B细胞淋巴瘤BJAB异种移植肿瘤模型中也显示出显着的体内功效。

  DOI：

  10.1016/j.ejmech.2018.10.066
• 作为产物：
  描述：

  5-bromo-1-(4-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indol-7-ylamine 在 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲苯 为溶剂， 反应 15.0h， 以90%的产率得到1-(4-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indol-7-ylamine
  参考文献：
  名称：

  7-芳酰基-氨基吲哚啉-1-磺酰胺是一类新的有效的抗微管蛋白药物。

  摘要：

  一系列新型的7-芳酰基-氨基二氢吲哚-1-苯磺酰胺通过与微管的秋水仙碱结合位点结合，表现出优异的微管蛋白聚合抑制剂活性。化合物15和16的IC50值分别为1.1和1.2 microM。化合物15抑制人癌细胞KB，MKN45，H460，HT29和TSGH的生长以及一种人抗性KB-vin 10癌细胞系，IC50为9.6、8.8、9.4、8.6、10.8和分别为8.9 nM。

  DOI：

  10.1021/jm061076u

文献信息

• Indoline-sulfonamides compounds
  申请人：Liou Jing-Ping

  公开号：US20080058386A1

  公开（公告）日：2008-03-06

  A series of indoline-sulfonamide compounds is disclosed. The formula of indoline-sulfonamide compounds is shown as formula (I). In formula (I), R 1 is H or halogen; R 2 is Ar, Ar—C(O)—, Ar—CH 2 —, Ar—SO 2 —, Ar—O—C(O), or R″—C(O)—, and Ar is a substituted or unsubstituted C5-C20 aryl, cyclyl, heterocyclyl, or heteroaryl, R′ and R″ independently is C1-C10 alkyl, or C1-C10 alkoxyl; and R 3 is C5-C15 aryl or C1-C10 alkyl. The indoline-sulfonamide compounds disclosed in the present invention are characterized in inhibiting tubulin polymerization, and treating cancers and other tubulin polymerization-related disorders with a suitable pharmaceutical acceptable carrier.

  公开了一系列吲哚啉-磺酰胺化合物。吲哚啉-磺酰胺化合物的公式如公式（I）所示。在公式（I）中，R1是H或卤素；R2是Ar，Ar—C(O)—，Ar—CH2—，Ar—SO2—，Ar—O—C(O)，或R″—C(O)—，其中Ar是取代或未取代的C5-C20芳基、环烷基、杂环基或杂芳基，R′和R″独立地是C1-C10烷基或C1-C10烷氧基；R3是C5-C15芳基或C1-C10烷基。本发明公开的吲哚啉-磺酰胺化合物具有抑制微管蛋白聚合的特性，并可与适当的药学上可接受的载体一起用于治疗癌症和其他与微管蛋白聚合相关的疾病。
• Synthesis of new carbon-11-labeled 7-aroyl-aminoindoline-1-sulfonamides as potential PET agents for imaging of tubulin polymerization in cancers
  作者：Min Wang、Mingzhang Gao、Kathy D. Miller、George W. Sledge、Gary D. Hutchins、Qi-Huang Zheng

  DOI：10.1002/jlcr.1462

  日期：2008.1

  The tubulin polymerization is an attractive target for anticancer therapy and in the development of cancer imaging agents for use in biomedical imaging technique positron emission tomography (PET). 7-Aroyl-aminoindoline-1-sulfonamides are a novel class of potent antitublin agents. Carbon-11-labeled 7-aroyl-aminoindoline-1-sulfonamides have been synthesized as new potential PET agents for imaging of tubulin polymerization in cancers. The target tracers were prepared by O-[11C]methylation of their corresponding precursors using [11C]CH3OTf and isolated by a simplified solid-phase extraction purification procedure in 40–55% radiochemical yields based on [11C]CO2 and decay corrected to the end of bombardment (EOB), 15–20 min overall synthesis time from EOB, >98% radiochemical purity, and 74–111 GBq/µmol specific activity at the end of synthesis. Copyright © 2008 John Wiley & Sons, Ltd.

  微管蛋白聚合是抗癌治疗和用于生物医学成像技术正电子发射断层扫描（PET）的癌症成像剂开发的一个有吸引力的靶点。7-芳酰基-氨基喃啶-1-磺酰胺是一种新型的有效抗微管蛋白药物。已合成碳-11标记的7-芳酰基-氨基喃啶-1-磺酰胺，作为用于成像癌症中微管蛋白聚合的新潜在PET试剂。通过使用[11C]CH3OTf对其相应前体进行O-[11C]甲基化，制备了目标示踪剂，并通过简化的固相提取纯化程序分离，辐射化学产率为40-55%（基于[11C]CO2），并经衰变校正至轰击结束（EOB），从EOB起总体合成时间为15-20分钟，辐射化学纯度超过98%，合成结束时特定活度为74-111 GBq/µmol。版权 © 2008 John Wiley & Sons, Ltd.
• Concise syntheses of 7-anilino-indoline-N-benzenesulfonamides as antimitotic and vascular disrupting agents
  作者：Samir Mehndiratta、Yi-Fang Chiang、Mei-Jung Lai、Hsueh-Yun Lee、Mei-Chuan Chen、Ching-Chuan Kuo、Chi-Yen Chang、Jang-Yang Chang、Jing-Ping Liou

  DOI：10.1016/j.bmc.2014.06.042

  日期：2014.9

  Described herein is the development of a novel series of 7-anilino-indoline-N-benzenesulfonamides, derived from ABT751 (1), as potent anticancer agents. Amongst the synthesized series, compounds 6, 12, 13, and 14 have shown comparable to better anticancer activity on comparing with compound 1. 7-(4-Cyanophenylamino)-1-(4-methoxybenzenesulfonyl)indoline (13) was found to be the most potent one with up to 6 fold better activity against KB, HT29, and MKN45 cancer cell lines with IC50 values of 49.7, 149, and 92nM, respectively. Compound 13 was also found inhibiting multidrug resistant cancer cell lines, blocking cell cycle at G2/M phase, and inhibiting tubulin polymerization. Capillary disruption assay results revealed that compound 13 was able to disrupt formed capillaries in a concentration-dependent manner without affecting cell viability.
• A novel tubulin polymerization inhibitor, MPT0B206, downregulates Bcr-Abl expression and induces apoptosis in imatinib-sensitive and imatinib-resistant CML cells
  作者：Chih-Wei Chen、Yueh-Lun Lee、Jing-Ping Liou、Yu-Hsiu Liu、Chin-Wei Liu、Tsai-Yun Chen、Huei-Mei Huang

  DOI：10.1007/s10495-016-1264-z

  日期：2016.9

  Imatinib, a Bcr-Abl-specific inhibitor, is effective for treating chronic myeloid leukemia (CML), but drug resistance has emerged for this disease. In this study, we synthesized a novel tubulin polymerization inhibitor, MPT0B206 (N-[1-(4-methoxy-benzenesulfonyl)-2,3-dihydro-1H-indol-7-yl]-formamide), and demonstrated its apoptotic effect and mechanism in imatinib-sensitive K562 and imatinib-resistant K562R CML cells. Western blotting and immunofluorescence microscopy showed that MPT0B206 induced microtubule depolymerization in K562 and K562R cells. MPT0B206 inhibited the growth of these cells in a concentration- and time-dependent manner. It did not affect the viability of normal human umbilical vein endothelial cells. MPT0B206 induced G2/M cell cycle arrest and the appearance of the mitotic marker MPM-2 in K562 and K562R cells, which is associated with the upregulation of cyclin B1 and the dephosphorylation of Cdc2. Treatment of K562 and K562R cells with MPT0B206 induced apoptosis and reduced the protein levels of procaspase-9 and procaspase-3 and increased caspase-3 activity and PARP cleavage. MPT0B206 also reduced the levels of the antiapoptotic proteins Mcl-1 and Bcl-2 and increased the level of the apoptotic protein Bax. Additional experiments showed that MPT0B206 markedly downregulated Bcr-Abl mRNA expression and total and phosphorylated Bcr-Abl protein levels and inhibited the phosphorylation of its downstream proteins STAT5, MAPK, and AKT, and the protein level of c-Myc in K562 and K562R cells. Furthermore, MPT0B206 triggered viability reduction and apoptosis in CML cells carrying T315I-mutated Bcr-Abl. Together, these results suggest that MPT0B206 is a promising alternative for treating imatinib-resistant CML.
• COMPOUNDS AND PHARMACEUTICAL COMPOSITION ASSOCIATED WITH UBIQUITINATION-PROTEASOME SYSTEM
  申请人：TAIPEI MEDICAL UNIVERSITY

  公开号：US20190144383A1

  公开（公告）日：2019-05-16

  The invention relates to new compounds with low cytotoxicity for blocking ubiquitination-proteasome system in diseases. Accordingly, these compounds can be used in treatment of treating disorders including, but not limited to, cancers, neurodegenerative diseases, inflammatory disorders and autoimmune disorders and metabolic disorders.