[4-benzyloxy-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl chloride | 413578-28-6

• 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: [4-benzyloxy-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl chloride
• 英文别名: 2-[4-benzyloxy-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl chloride；N-[1-(2-chloroethyl)-4-phenylmethoxynaphthalen-2-yl]-5,6,7-trimethoxy-1H-indole-2-carboxamide
• CAS: 413578-28-6
• 化学式: C₃₁H₂₉ClN₂O₅
• 分子量: 545.035
• InChiKey: JOFFSFBROBVBCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-benzyloxy-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl chloride 在 钯 氢气 、 乙醚 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以to yield 4-(2-chloroethyl)-3-(5,6,7-trimethoxyindole-2-carboxamido)-1-naphthol (54 mg, 91%) as a white solid的产率得到4-(2-chloroethyl)-3-(5,6,7-trimethoxyindole-2-carboxamido)-1-naphthol
  参考文献：
  名称：

  Compositions and methods of the use thereof achiral analogues of CC-1065 and the duocarmycins

  摘要：

  本发明涉及新型非手性的DNA小槽和序列选择性烷基化剂的二级类似物，包括一般的I、II、III、IV和V类，如(+) -CC1065和duocarmycins，其中X是良好的离去基团，例如氯化物、溴化物、碘化物、甲磺酸盐、对甲苯磺酸盐、乙酸盐、季铵基团、巯基、烷基硫氧基或烷基磺酰基，优选氯化物、溴化物或碘化物基团。R1是适当的小槽结合剂，以增强非手性的二级环丙烷吲哚(Cl)或非手性的二级duocarmycin与DNA特定序列的相互作用。

  公开号：

  US06660742B2
• 作为产物：
  描述：

  氯硝萘 在 platinum(IV) oxide 吡啶 、 盐酸 、 sodium sulfide 、 硫酸 、 氢气 、 二异丁基氢化铝 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 60.0 ℃ 、379.21 kPa 条件下， 反应 196.83h， 生成 [4-benzyloxy-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl chloride
  参考文献：
  名称：

  A Novel Class of in Vivo Active Anticancer Agents:  Achiral seco-Amino- and seco-Hydroxycyclopropylbenz[e]indolone (seco-CBI) Analogues of the Duocarmycins and CC-1065

  摘要：

  One achiral seco-hydroxycyclopropylbenz[e]indolone (seco-CBI) (12) and seven achiral seco-amino-CBI (11a-g) analogues of CC-1065 and the duocarmycins were designed, synthesized and evaluated for their DNA-binding and anticancer properties. These compounds contain a core 2-chloroethylnaphthalene structure and they do not have a stereocenter. From thermal cleavage gel analyses, compounds 11a-g and 12 demonstrated similar covalent sequence specificity to adozelesin 3 and the racemic seco-CBI-TMI 4 for binding to the 5'-AAAAA(865)-3' site. Continuous exposure of human (K562) and murine (B16, L1210 and P815) cancer cell lines to the compounds demonstrated their significant cytotoxicity, with IC50 values in the sub-micromolar range. Generally, a good leaving group on the ethyl moiety and a free amino or hydroxyl group on the naphthyl moiety are essential for activity. According to NCI's cytotoxicity screen, compounds 11a and 12 were active against human cancer cell lines derived from lung, colon, melanoma, renal system, and breast. At the respective doses of 15 and 20 mg/kg (administered via an ip route), compounds 11a and 12 inhibited the growth of murine B16-F0 melanoma in C57BL/6 mice, with minimal toxicity, and 11a gave a significant anticancer effect. The in vivo anticancer activity of compound 11a was confirmed in a human tumor xenograft study (advanced stage SC-OVCAR-3 ovarian cancer growing in scid mice). Finally, compound 11a was not toxic to murine bone marrow cell growth in culture at a dose that was toxic for the previously reported compound 4.

  DOI：

  10.1021/jm050179u

文献信息

• Efficient Synthesis of Achiral <i>s</i><i>eco</i>-Cyclopropylbenz[2,3-<i>e</i>]indoline Analogues:  [4-Amino-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl Chloride and [4-Hydroxy-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl Chloride
  作者：Atsushi Sato、Adrienne Scott、Tetsuji Asao、Moses Lee

  DOI：10.1021/jo060501o

  日期：2006.6.1

  Achiral seco-aminocyclopropylbenz[ 2,3-e] indoline and secohydroxycyclopropylbenz[ 2,3-e] indoline ( seco-CBI) analogues of the duocarmycins and CC-1065, e. g., 7 and 8, are potent anticancer agents. This paper describes significantly improved synthetic strategies for preparing these compounds. Starting from Martius acid ( 9), the new strategy gave a 13-fold increase in the overall yield of 7, and the use of ditertbutyl malonate was economically beneficial. For compound 8, the new strategy employed an Emmons-Horner reaction, followed by a Stobbe condensation, and the overall yield was improved 15-fold.
• COMPOSITIONS AND METHODS OF THE USE THEREOF ACHIRAL ANALOGUES OF CC-1065 AND THE DUOCARMYCINS
  申请人：Lee, Moses

  公开号：EP1320522B8

  公开（公告）日：2006-02-01
• US6660742B2
  申请人：——

  公开号：US6660742B2

  公开（公告）日：2003-12-09
• [EN] COMPOSITIONS AND METHODS OF THE USE THEREOF ACHIRAL ANALOGUES OF CC-1065 AND THE DUOCARMYCINS<br/>[FR] COMPOSITIONS ET LEURS METHODES D'UTILISATION, ANALOGUES ACHIRAUX DE CC-1065 ET DE DUOCARMYCINES
  申请人：TAIHO PHARMACEUTICAL CO LTD

  公开号：WO2002030894A2

  公开（公告）日：2002-04-18

  The present invention relates to novel achiral seco-analogues of the DNA minor groove and sequence-selective alkylating agents (+)-CC1065 and the duocarmycins, depicted as general class (I), (II), (III), (IV) and (V) wherein X is a good leaving group, such as chloride, a bromide, an iodide, a mesylate, a tosylate, an acetate, a quaternary ammonium moiety, a mercaptan, an alkylsulfoxyl, or an alkylsulfonyl group, preferably either a chloride, a bromide, or an iodide group. R1 is a suitable minor groove binding agent to enhance the interactions of the achiral seco-cyclopropaneindole (CI) or an achiral seco-duocarmycin with specific sequences of DNA. R and R2-R5 are defined in claim 1.