5-<2-(dimethylamino)ethoxy>-1H-indole-2-carboxylic acid | 557772-39-1

• 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-<2-(dimethylamino)ethoxy>-1H-indole-2-carboxylic acid
• 英文别名: 5-[2-(dimethylamino)ethoxy]-1H-indole-2-carboxylic acid；5-(2-dimethylaminoethoxy)indole-2-carboxylic acid；5-(2-N,N-dimethylamino-ethoxy)-1H-indole-2-carboxylic acid；5-(2-(Dimethylamino)ethoxy)-1H-indole-2-carboxylic acid
• CAS: 557772-39-1
• 化学式: C₁₃H₁₆N₂O₃
• 分子量: 248.282
• InChiKey: GSIOXRJRNJLKNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  65.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-<2-(dimethylamino)ethoxy>-1H-indole-2-carboxylic acid 在 吡啶 、 对甲苯磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 1.67h， 生成 (7-((2-((di-tert-butoxyphosphoryl)oxy)ethyl)carbamoyl)-3-(5-(2-(dimethylamino)ethoxy)-1H-indole-2-carbonyl)-5-nitro-2,3-dihydro-1H-benzo[e]indol-1-yl)methyl phenylmethanesulfonate
  参考文献：
  名称：

  硝基塞科的卡霉素含磺酸酯基离去基团为类似物低氧激活的前体药物治疗癌症

  摘要：

  报道了19（5-硝基-2,3-二氢-1 H-苯并[ e ]吲哚-1-基）甲基磺酸盐前药的合成，该药物含有磺酸盐离去基团和7-取代的吸电子基团。这些被设计用于进行缺氧选择性代谢，以形成有效的DNA小沟烷基化剂。类似物17和24，包含磺酸苄酯离去基团和中性DNA小沟结合侧链，在体外抗增殖试验中显示HT29人癌细胞的缺氧细胞毒性比（HCR）> 1000。四个类似物在一组八种人类癌细胞系中维持较大的HCR。在克隆形成分析中，19HT29细胞的HCR显示为4090。还制备了十种可溶性磷酸盐前药，并以无毒剂量在体内，单独或与放射联合在SiHa人肿瘤异种移植物中进行了评估。化合物34和39的缺氧log 10细胞杀伤（LCK）分别为1.78和2.71，与先前报道的氯化物或溴化物类似物具有同等或更高的活性，因此显示出作为缺氧激活的前药的杰出前景。

  DOI：

  10.1021/jm201717y
• 作为产物：
  描述：

  5-羟基吲哚-2-甲酸 在 盐酸 、 水 、 potassium carbonate 、 caesium carbonate 作用下， 以 甲醇 、 氯仿 、 水 为溶剂， 反应 23.0h， 生成 5-<2-(dimethylamino)ethoxy>-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  Initial development of a cytotoxic amino-seco-CBI warhead for delivery by prodrug systems

  摘要：

  Cyclopropabenzaindoles (CBIs) are exquisitely potent cytotoxins which bind and alkylate in the minor groove of DNA. They are not selective for cancer cells, so prodrugs are required. CBIs can be formed at physiological pH by Winstein cyclisation of 1-chloromethyl-3-substituted-5-hydroxy-2,3-dihydro-benzo[e] indoles (5-OH-seco-CBIs). Corresponding 5-NH2-seco-CBIs should also undergo Winstein cyclisation similarly. A key triply orthogonally protected intermediate on the route to 5-NH2-seco-CBIs has been synthesised, via selective monotrifluoroacetylation of naphthalene-1,3-diamine, Boc protection, electrophilic iodination, selective allylation at the trifluoroacetamide and 5-exo radical ring-closure with TEMPO. This intermediate has potential for introduction of peptide prodrug masking units (deactivating the Winstein cyclisation and cytotoxicity), addition of diverse indole-amide side-chains (enhancing non-covalent binding prior to alkylation) and use of different leaving groups (replacing the usual chlorine, allowing tuning of the rate of Winstein cyclisation). This key intermediate was elaborated into a simple model 5-NH2-seco-CBI with a dimethylaminoethoxyindole side-chain. Conversion to a bio-reactive entity and the bioactivity of this system were confirmed through DNA-melting studies (Delta T-m = 13 degrees C) and cytotoxicity against LNCaP human prostate cancer cells (IC50 = 18 nM). (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.034
• 作为试剂：
  描述：

  5-<2-(dimethylamino)ethoxy>-1H-indole-2-carboxylic acid 、 4-(3-amino-prop-1-ynyl)benzoic acid methyl ester hydrochloride 在 5-<2-(dimethylamino)ethoxy>-1H-indole-2-carboxylic acid 作用下， 生成 4-(3-{5-[2-(dimethylamino)-ethoxy]-1H-indole-2-carbonylamino}-prop-1-ynyl)-benzoic acid methyl ester
  参考文献：
  名称：

  Acetylene derivatives as inhibitors of histone deacetylase

  摘要：

  本发明涉及某些羟酰胺衍生物，它们是组蛋白去乙酰化酶的抑制剂，因此在治疗与组蛋白去乙酰化酶活性相关的疾病方面是有用的。同时还公开了制备这些化合物的制药组合物和过程。

  公开号：

  US07368572B2

文献信息

• [EN] ACETYLENE DERIVATIVES AS INHIBITORS OF HISTONE DEACETYLASE<br/>[FR] DERIVES D'ACETYLENE EN TANT QU'INHIBITEURS D'HISTONE DEACETYLASE
  申请人：AXYS PHARM INC

  公开号：WO2005019174A1

  公开（公告）日：2005-03-03

  The present invention is directed to certain hydroxamate derivatives that are inhibitors of histone deacetylase and are therefore useful in the treatment of diseases associated with histone deacetylase activity. Pharmaceutical compositions and processes for preparing these compounds are also disclosed.

  本发明涉及某些羟肟酸酯衍生物，它们是组蛋白去乙酰化酶的抑制剂，因此在治疗与组蛋白去乙酰化酶活性相关的疾病方面具有用处。还公开了制备这些化合物的药物组合物和方法。
• Mesylate salt of 5-(2-dimethylaminoethoxy)-1H-indole-2-carboxylic acid [3-(4-hydroxycarbamoylphenyl)prop-2-ynyl]amide
  申请人：Verner J. Erik

  公开号：US20070105939A1

  公开（公告）日：2007-05-10

  The present invention is directed to the mesylate salt of 5-(2-dimethylamino-ethoxy)-1H-indole-2-carboxylic acid [3-(4-hydroxycarbamoylphenyl)prop-2-ynyl]amide, pharmaceutical compositions and processes for preparing the same.

  本发明涉及5-(2-二甲基氨基乙氧基)-1H-吲哚-2-羧酸[3-(4-羟基氨甲酰基苯基)丙-2-炔基]酰胺的甲磺酸盐，药物组合物以及制备该盐的方法。
• Water-Soluble CC-1065 Analogs and Their Conjugates
  申请人：Beusker Patrick Henry

  公开号：US20090318668A1

  公开（公告）日：2009-12-24

  This invention relates to novel analogs of the DNA-binding alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and their conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

  这项发明涉及DNA结合烷基化剂CC-1065的新型类似物及其结合物。此外，该发明涉及用于制备上述剂和它们的结合物的中间体。这些结合物设计为在一个或多个激活步骤之后以及/或由结合物控制的速率和时间跨度下释放它们的（多种）荷载，以便选择性地传递和/或可控地释放一个或多个所述的DNA烷基化剂。这些剂、结合物和中间体可用于治疗以不良（细胞）增殖为特征的疾病。例如，这项发明的剂和结合物可用于治疗肿瘤。
• [EN] SECO-CYCLOPROPAPYRROLOINDOLE COMPOUNDS, ANTIBODY-DRUG CONJUGATES THEREOF, AND METHODS OF MAKING AND USE<br/>[FR] COMPOSÉS DE SECO-CYCLOPROPAPYRROLOINDOLE, CONJUGUÉS ANTICORPS-MÉDICAMENT DE CEUX-CI, ET PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2018035391A1

  公开（公告）日：2018-02-22

  seco-Cyclopropapyrroloindole compounds of formula (I) where Hal, R1, R2, and R3 are as defined in the application, are potent anti-cancer agents that can be used in antibody-drug conjugates.

  公式（I）中的seco-Cyclopropapyrroloindole化合物，其中Hal、R1、R2和R3如申请中定义，是强效的抗癌药物，可以用于抗体药物偶联物。
• [EN] SUBSTITUTED CC-1065 ANALOGS AND THEIR CONJUGATES<br/>[FR] ANALOGUES CC-1065 SUBSTITUÉS ET LEURS CONJUGUÉS
  申请人：SYNTARGA BV

  公开号：WO2009017394A1

  公开（公告）日：2009-02-05

  This invention relates to novel agents that are analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and their conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

  本发明涉及一种与DNA-烷基化剂CC-1065类似的新型剂，以及它们的共轭物。此外，本发明涉及用于制备所述剂和它们的共轭物的中间体。共轭物被设计为在一个或多个激活步骤后释放它们的（多个）有效载荷和/或由共轭物控制的速率和时间跨度，以有选择地传递和/或可控释放一个或多个所述的DNA烷基化剂。这些剂、共轭物和中间体可用于治疗其特征为不受欢迎的（细胞）增殖的疾病。例如，本发明的剂和共轭物可用于治疗肿瘤。