1-(chloromethyl)-N-prop-2-enyl-2,3-dihydro-1H-benzo[e]indol-5-amine | 1017279-61-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(chloromethyl)-N-prop-2-enyl-2,3-dihydro-1H-benzo[e]indol-5-amine
• CAS: 1017279-61-6
• 化学式: C₁₆H₁₇ClN₂
• 分子量: 272.777
• InChiKey: NISWLFNVKDBMBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(chloromethyl)-N-prop-2-enyl-2,3-dihydro-1H-benzo[e]indol-5-amine 在 Grubbs catalyst first generation 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲苯 为溶剂， 反应 8.0h， 生成 (2E)-1-[5-amino-1-(chloromethyl)-1H,2H,3H-benzo[e]indol-3-yl]-3-(4-methoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  3-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚（氨基-CBI）的新短合成。

  摘要：

  公开了一种来自Martius Yellow的3-取代的5-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚的新的短合成物。合成的关键步骤是三个有效的区域选择性反应（碘化，5-exo-trig芳基自由基-烯烃环化和羧化）。

  DOI：

  10.1021/jo0263115
• 作为产物：
  描述：

  1,3-萘二胺 在 四氯化碳 、 N-碘代丁二酰亚胺 、 三正丁基氢锡 、 sodium hydride 、 对甲苯磺酸 、 三苯基膦 、 三氟乙酸 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 27.25h， 生成 1-(chloromethyl)-N-prop-2-enyl-2,3-dihydro-1H-benzo[e]indol-5-amine
  参考文献：
  名称：

  3-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚（氨基-CBI）的新短合成。

  摘要：

  公开了一种来自Martius Yellow的3-取代的5-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚的新的短合成物。合成的关键步骤是三个有效的区域选择性反应（碘化，5-exo-trig芳基自由基-烯烃环化和羧化）。

  DOI：

  10.1021/jo0263115

文献信息

• [EN] PROCESSES FOR PREPARING 3-SUBSTITUTED 1-(CHLOROMETHYL)-1,2-DIHYDRO-3H-[RING FUSED INDOL-5-YL(AMINE-DERIVED)] COMPOUNDS AND ANALOGUES THEREOF, AND TO PRODUCTS OBTAINED THEREFROM<br/>[FR] PROCEDE DE PREPARATION DE COMPOSES DE 3-SUBSTITUE 1-(CHLOROMETHYL)-1,2-DIHYDRO-3H [-5-YL A CYCLES FUSIONNES (DERIVES D'AMINE)] ET DE LEURS ANALOGUES, ET PRODUITS DERIVES
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2003097635A1

  公开（公告）日：2003-11-27

  The invention provides processes of preparing 3-substituted 1-(chloromethyl)-1,2-dihydro-3H-[ring fused indol-5-yl(amine-derived)] compounds of formula (I) and its analogues, or a physiologically functional derivative thereof, (I), wherein A and B together may represent a fused optionally substituted benzene, naphthalene, pyridine, furan or a pyrrole ring, where the optional substituents are represented by Y; X is halogen or OSO2R , and W is selected from NO2, NHOH, N(R3)2NHR3, NHCO2R3, N(phthaloyl) or NH2, or W is further selected from the group (a) , wherein J is selected from OH or R, and P is a group which is a substrate suitable for a nitroreductase or carboxypeptidase enzyme. The invention is also directed to the use of compounds of formula (I) prepared by the processes of the invention as cytotoxins for cancer therapy and as prodrugs for gene-directed enzyme-prodrug therapy (GDEPT) and antibody-directed enzyme-prodrug therapy (ADEPT).

  该发明提供了制备公式（I）及其类似物的3-取代1-(氯甲基)-1,2-二氢-3H-[环融合吲哚-5-基（衍生自胺基）]化合物的过程，或其生理功能衍生物，其中A和B一起可以表示一个融合的可选取代苯、萘、吡啶、呋喃或吡咯环，其中可选取代基由Y表示；X为卤素或OSO2R，W从NO2、NHOH、N(R3)2NHR3、NHCO2R3、N(邻苯二甲酰基)或NH2中选择，或W进一步从群（a）中选择，其中J从OH或R中选择，P是适用于硝基还原酶或羧肽酶的底物基团。该发明还涉及通过该发明的过程制备的公式（I）化合物作为抗癌细胞毒素以及基因导向酶-前药疗法（GDEPT）和抗体导向酶-前药疗法（ADEPT）的前药的用途。
• BIS-ALKYLATING AGENTS AND THEIR USE IN CANCER THERAPY
  申请人：Szekely Zoltan

  公开号：US20090118349A1

  公开（公告）日：2009-05-07

  The present invention relates to (i) conjugates comprising two DNA alkylating subunits linked by a moiety fitting to the minor groove of the DNA, (ii) to their preparation and (iii) to their use in cancer therapy. The alkylating subunits are especially cytotoxic under hypoxic conditions found in cancer cells. The compounds of the present invention and compositions thereof are useful in the treatment of cancer in a mammal, both alone or in a combination with other anti-cancer agents (e.g. checkpoint abrogators) and/or radiation. They may also be used as cytotoxic units for gene-directed enzyme-prodrug therapy (GDEPT) and antibody-directed enzyme-prodrug therapy (ADEPT). The present invention provides the compounds of Formula (I), Formula (II) and Formula (III): for treating cancer in a mammal.

  本发明涉及（i）由适合于DNA小沟的基团连接的两个DNA烷基化亚基组成的共轭物，（ii）它们的制备和（iii）它们在癌症治疗中的应用。烷基化亚基在癌细胞中发现的低氧条件下特别具有细胞毒性。本发明的化合物及其组合物在哺乳动物中治疗癌症方面具有用途，可以单独使用或与其他抗癌药物（例如检查点阻断剂）和/或放射线结合使用。它们还可以用作基因定向酶-前药疗法（GDEPT）和抗体定向酶-前药疗法（ADEPT）的细胞毒性单位。本发明提供了式（I）、式（II）和式（III）的化合物，用于哺乳动物中治疗癌症。
• Weight loss effects of quaternary salts of 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indoles; structure–activity relationships
  作者：Moana Tercel、Ralph J. Stevenson、Guo-Liang Lu、Stephen M. Stribbling、William R. Wilson、Michele A. Tatnell、Rebecca N. Marnane、Kathleen G. Mountjoy、William A. Denny

  DOI：10.1016/j.bmc.2011.12.007

  日期：2012.1

  Quaternary salt analogues based on the DNA minor groove binder and adenine N3 alkylating agent 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benz[e]indole (aminoCBI) show remarkable effects on the body weight of mice (a long-term failure to gain weight relative to matched controls with no loss of appetite or perceptible deterioration in health) following administration of a single (non-toxic) dose between about 0.5-5 mu mol/kg. The nature of the quaternizing group was not important, but a related hydroxyCBI analogue was much less effective. Compounds where the chloro group was replaced by a hydrogen or hydroxy group (thus abrogating DNA alkylating capability) showed no weight control activity. It is speculated, based on other studies, that the marked long-term weight control effect is due to inhibition of bile flow into the intestine and reduced absorption of triglycerides, together with accelerated cell death in spleen and white adipose tissues due to drug accumulation there. This class of compound may serve as interesting tools for further study of these phenomena. (C) 2011 Elsevier Ltd. All rights reserved.
• A New Short Synthesis of 3-Substituted 5-Amino-1-(chloromethyl)-1,2-dihydro-3<i>H</i>-benzo[<i>e</i>]indoles (Amino-CBIs)
  作者：Shangjin Yang、William A. Denny

  DOI：10.1021/jo0263115

  日期：2002.12.1

  A new short synthesis of 3-substituted 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indoles from Martius Yellow is disclosed. The key steps of the synthesis were three efficient regioselective reactions (iodination, 5-exo-trig aryl radical-alkene cyclization and carboxylation).

  公开了一种来自Martius Yellow的3-取代的5-取代的5-氨基-1-（氯甲基）-1，2-二氢-3H-苯并[e]吲哚的新的短合成物。合成的关键步骤是三个有效的区域选择性反应（碘化，5-exo-trig芳基自由基-烯烃环化和羧化）。