(5-methoxy-1H-indol-1-yl)(3,4,5-trimethoxyphenyl)methanone

• 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: (5-methoxy-1H-indol-1-yl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: (5-methoxy-indol-1-yl)-(3,4,5-trimethoxy-phenyl)-methanone；(5-methoxyindol-1-yl)-(3,4,5-trimethoxyphenyl)methanone；5-Methoxy-1-(3,4,5-trimethoxybenzoyl)indole
• 化学式: C₁₉H₁₉NO₅
• 分子量: 341.364
• InChiKey: CXPQVGCOUWHQMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  58.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-甲氧基吲哚 、 3,4,5-三甲氧基苯甲酸酐 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 1.17h， 以94%的产率得到(5-methoxy-1H-indol-1-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Discovery of 4-Amino and 4-Hydroxy-1-aroylindoles as Potent Tubulin Polymerization Inhibitors

  摘要：

  1-Aroylindoline, 1-aroyl-1,2,3,4-tetrahydroquinoline, and 1-aroylindole derivatives were synthesized and evaluated for anticancer activity. The 4-amino and 4-hydroxy-1-aroylindoles 26 and 27 with IC(50) Of 0.9 and 0.6 mu M, respectively, exhibited antitubulin activity superior or comparable to that of colchicine and combretastatin A-4. They also showed antiproliferative activity with IC(50) of 0.3-5.4 nM in a set of human cancer cell lines.

  DOI：

  10.1021/jm800150d

文献信息

• [EN] COMBRETASTATIN DERIVATIVES AND USES THEREFOR<br/>[FR] DÉRIVÉS DE COMBRÉTASTATINE ET LEURS APPLICATIONS
  申请人：TRINITY COLLEGE DUBLIN

  公开号：WO2011073211A1

  公开（公告）日：2011-06-23

  Cancer is one of the major causes of death worldwide. Although many advances have been made in the treatment and management of the disease, the existence of chemotherapy-resistance means there is still a great need to develop new strategies and drugs for its treatment. Provided herein are synthetic derivatives of combretastatin A-4, in particular those in which the aromatic rings are locked into a non-isomerisable active conformation, thus resulting in improved, stable compounds. The novel compounds are structurally related to combretastatin A-4 (CA-4) and lock the rings into the known active conformation by means of a four membered nitrogen containing heterocyclic ring, such as a beta-lactam ring, incorporated into the standard CA-4 structure. The compounds exhibit potent anti-cancer activity.

  癌症是全球主要死因之一。尽管在治疗和管理该疾病方面取得了许多进展，但化疗耐药的存在意味着仍然迫切需要开发新的治疗策略和药物。本文提供了紫杉醇A-4的合成衍生物，特别是那些其中芳香环被锁定为非可异构活性构象，从而产生改进的稳定化合物。这些新颖的化合物在结构上与紫杉醇A-4（CA-4）相关，并通过将一个含氮杂环环（如β-内酰胺环）并入标准CA-4结构来将环锁定为已知的活性构象。这些化合物表现出强大的抗癌活性。
• Combretastatin Derivatives and Uses Therefor
  申请人：The Provost, Fellows and Scholars of the College of the Holy and Undivided Trinity of Queen Elizabeth near Dublin

  公开号：EP2338877A1

  公开（公告）日：2011-06-29

  Provided herein are synthetic derivatives of combretastatin A-4 in which the aromatic rings are locked into a non-isomerisable active conformation, thus resulting in improved, stable compounds. The novel compounds are structurally related to combretastatin A-4 (CA-4) and lock the rings into the known active conformation by means of a four membered nitrogen containing heterocyclic ring, such as a beta-lactam ring, incorporated into the standard CA-4 structure. The compounds exhibit potent anti-cancer activity.

  本文提供的是康柏他定A-4的合成衍生物，其中芳香环被锁定在一种不可异构的活性构象中，从而导致改进的、稳定的化合物。这些新颖的化合物在结构上与康柏他定A-4（CA-4）相关，并通过将一个含氮的四元杂环环（如β-内酰胺环）并入标准的CA-4结构中，将环锁定在已知的活性构象中。这些化合物表现出强大的抗癌活性。
• Concise Synthesis and Structure−Activity Relationships of Combretastatin A-4 Analogues, 1-Aroylindoles and 3-Aroylindoles, as Novel Classes of Potent Antitubulin Agents
  作者：Jing-Ping Liou、Yi-Ling Chang、Fu-Ming Kuo、Chun-Wei Chang、Huan-Yi Tseng、Chiung-Chiu Wang、Yung-Ning Yang、Jang-Yang Chang、Shiow-Ju Lee、Hsing-Pang Hsieh

  DOI：10.1021/jm049802l

  日期：2004.8.1

  activities. Structure-activity relationships revealed that 6-methoxy substitution of 3-aroylindoles and 5-methoxy substitution of 1-aroylindoles contribute to a significant extent for maximal activity by mimicking the para substitution of the methoxy group to the carbonyl group in the case of aminobenzophenones. Addition of a methyl group at the C-2 position on the indole ring exerts an increased potency

  描述了基于1-芳基吲哚和3-芳基吲哚骨架的两类新的合成抗微管蛋白化合物的结构-活性关系的合成和研究。铅化合物3、10和14对人NUGC3胃，MKN45胃，MESSA子宫，A549肺和MCF-7乳腺癌细胞系表现出有效的细胞毒性，IC50 = 0.9-26 nM。增殖的抑制与体外聚合抑制活性有关。结构活性关系表明，在氨基二苯甲酮的情况下，通过模仿甲氧基对羰基的对位取代，3-芳基吲哚的6-甲氧基取代和1-芳酰基吲哚的5-甲氧基取代在很大程度上发挥了最大活性。在吲哚环的C-2位加甲基会增加效力。3，4，5-三甲氧基苯甲酰基部分对于更好的活性是必需的，但不是必需的，并且可以被3，5-二甲氧基苯甲酰基和3，4，5-三甲氧基苄基部分取代。我们得出结论，1-和3-芳基吲哚构成了有趣的一类新的抗微管蛋白药物，具有在临床上开发用于癌症治疗的潜力。
• Discovery of indoline derivatives that inhibit esophageal squamous cell carcinoma growth by Noxa mediated apoptosis
  作者：Dong-Jun Fu、Miaomiao Li、Sai-Yang Zhang、Jiang-Feng Li、Beibei Sha、Longhao Wang、Yan-Bing Zhang、Ping Chen、Tao Hu

  DOI：10.1016/j.bioorg.2019.103190

  日期：2019.11

  compound 20 inhibited cell growths in vitro and in vivo, reduced colony formation, arrested cell cycle at M phase, and induced Noxa-dependent apoptosis in ESCC. Importantly, compound 20 was identified as a novel Noxa mediated apoptosis inducer. These results suggested that compound 20 might be a promising anticancer agent with potential for development of further clinical applications.

  合成了一系列新型的吲哚啉衍生物，并评估了其对四种所选癌细胞系（Hela，A549，HepG2和KYSE30）的抗增殖活性。其中，化合物20显示出对食道癌细胞的有效抑制活性（Kyse30，Kyse450，Kyse510和EC109）。在食管鳞状细胞癌的细胞机制的研究（ESCC）细胞阐明化合物20抑制细胞生长的体外和体内，在M期减少集落形成，细胞周期阻滞，并在诱导ESCC Noxa的依赖性细胞凋亡。重要的是，化合物20被确定为新型的Noxa介导的细胞凋亡诱导剂。这些结果表明化合物20 可能是一种有前途的抗癌药，具有开发进一步临床应用的潜力。
• Indole compounds
  申请人：——

  公开号：US20030195244A1

  公开（公告）日：2003-10-16

  Indole compounds of the formula: 1 wherein L 1 is CO; L 2 is a bond; R 1 is aryl or heteroaryl; R 2 is H, aryl, heteroaryl, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO 2 R, SO 3 R, SO 2 NRR′, SR, NRR′, NRSO 2 NR′R″, NRSO 2 R′, NRSO 3 R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)OR, or C(O)NRR′; each of R a , R b , R c , and R d , independently, is R, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO 2 R, SO 3 R, SO 2 NRR′, SR, NRR′, NRSO 2 NR′R″, NRSO 2 R′, NRSO 3 R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, C(O)NRR′, or R b and R c , R a and R b , or R c and R d taken together are O(CH 2 ) n O; and R c is H, alkyl, alkenyl, alkynyl, cyclyl, heterocyclyl, halogen, nitro, nitroso, cyano, azide, isothionitro, OR, OC(O)R, OC(O)OR, OC(O)NRR′, SO 2 R, SO 3 R, SO 2 NRR′, SR, NRR′, NRSO 2 NR′R″, NRSO 2 R′, NRSO 3 R′, NRC(O)R′, NRC(O)NR′R″, NRC(O)OR′, NRC(N)NR′R″, C(O)R, C(O)OR, or C(O)NRR′; in which each of R, R′, and R″, independently, is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, cyclyl, or heterocyclyl; and n is 1, 2, 3, 4, or 5.

  公式为1的吲哚类化合物： 其中L1为CO；L2为键；R1为芳基或杂环芳基；R2为H、芳基、杂环芳基、卤素、硝基、亚硝基、氰基、偶氮基、异硫氰基、OR、OC(O)R、OC(O)OR、OC(O)NRR′、SO2R、SO3R、SO2NRR′、SR、NRR′、NRSO2NR′R″、NRSO2R′、NRSO3R′、NRC(O)R′、NRC(O)NR′R″、NRC(O)OR′、NRC(N)NR′R″、C(O)OR或C(O)NRR′；每个Ra、Rb、Rc和Rd，独立地为R、卤素、硝基、亚硝基、氰基、偶氮基、异硫氰基、OR、OC(O)R、OC(O)OR、OC(O)NRR′、SO2R、SO3R、SO2NRR′、SR、NRR′、NRSO2NR′R″、NRSO2R′、NRSO3R′、NRC(O)R′、NRC(O)NR′R″、NRC(O)OR′、NRC(N)NR′R″、C(O)R、C(O)OR、C(O)NRR′、Rb和Rc、Ra和Rb、或Rc和Rd结合成O(CH2)nO；Rc为H、烷基、烯基、炔基、环烷基、杂环烷基、卤素、硝基、亚硝基、氰基、偶氮基、异硫氰基、OR、OC(O)R、OC(O)OR、OC(O)NRR′、SO2R、SO3R、SO2NRR′、SR、NRR′、NRSO2NR′R″、NRSO2R′、NRSO3R′、NRC(O)R′、NRC(O)NR′R″、NRC(O)OR′、NRC(N)NR′R″、C(O)R、C(O)OR或C(O)NRR′；其中每个R、R′和R″独立地为H、烷基、烯基、炔基、芳基、杂环芳基、环烷基或杂环烷基；n为1、2、3、4或5。