4-(2-chloroethyl)-3-(5-nitroindole-2-carboxamido)phenol | 413577-19-2

• 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: 4-(2-chloroethyl)-3-(5-nitroindole-2-carboxamido)phenol
• 英文别名: N-[2-(2-chloroethyl)-5-hydroxyphenyl]-5-nitro-1H-indole-2-carboxamide
• CAS: 413577-19-2
• 化学式: C₁₇H₁₄ClN₃O₄
• 分子量: 359.769
• InChiKey: KPUSFGRUUAWOOZ-UHFFFAOYSA-N

物化性质

• 沸点：
  555.8±50.0 °C(Predicted)
• 密度：
  1.529±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  111
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-chloroethyl)-3-(5-nitroindole-2-carboxamido)phenol 在 palladium on activated charcoal 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 4-(2-chloroethyl)-3-[[5-(4-bis-(2-chloroethyl)amino)benzamido]indole-2-carboxamido]phenol
  参考文献：
  名称：

  一类新型的CC-1065和duocarcincin的非手性类似物：设计，合成，DNA结合和抗癌特性。

  摘要：

  描述了CC-1065和双carocin的十五种非手性seco-环丙基二氢吲哚啉（或非手性seco-CI）类似物（5a-o）的合成，DNA结合特性以及体外和体内抗癌活性。非手性seco-CI类似物包含4-羟基苯乙基卤化物部分，该部分与各种吲哚，苯并咪唑，吡咯和含吡啶基的非共价结合组分相连。4-羟基苯乙基卤化物部分代表天然产物中存在的癸二环丙基吡咯并吲哚啉（seco-CPI）药效团的最简单模拟物，并且缺少手性中心。使用Taq DNA聚合酶终止测定和使用pBR322或pUC18质粒DNA片段的热诱导DNA切割实验确定了非手性化合物的序列和微小凹槽特异性。例如，seco-CI-InBf（5a）和seco-CI-TMI（5c）显示了对富含AT的序列的特异性，特别是通过与5'-AAAAA（865）-3'的下划线腺嘌呤-N3位置反应。这也是CC-1065和adozelesin偏爱烷基化的顺序。对非手性s

  DOI：

  10.1016/j.bmc.2004.08.051
• 作为产物：
  描述：

  4-benzyloxy-2-nitrophenylacetic acid 在 palladium on activated charcoal 四氯化碳 、 硼烷 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 4-(2-chloroethyl)-3-(5-nitroindole-2-carboxamido)phenol
  参考文献：
  名称：

  一类新型的CC-1065和duocarcincin的非手性类似物：设计，合成，DNA结合和抗癌特性。

  摘要：

  描述了CC-1065和双carocin的十五种非手性seco-环丙基二氢吲哚啉（或非手性seco-CI）类似物（5a-o）的合成，DNA结合特性以及体外和体内抗癌活性。非手性seco-CI类似物包含4-羟基苯乙基卤化物部分，该部分与各种吲哚，苯并咪唑，吡咯和含吡啶基的非共价结合组分相连。4-羟基苯乙基卤化物部分代表天然产物中存在的癸二环丙基吡咯并吲哚啉（seco-CPI）药效团的最简单模拟物，并且缺少手性中心。使用Taq DNA聚合酶终止测定和使用pBR322或pUC18质粒DNA片段的热诱导DNA切割实验确定了非手性化合物的序列和微小凹槽特异性。例如，seco-CI-InBf（5a）和seco-CI-TMI（5c）显示了对富含AT的序列的特异性，特别是通过与5'-AAAAA（865）-3'的下划线腺嘌呤-N3位置反应。这也是CC-1065和adozelesin偏爱烷基化的顺序。对非手性s

  DOI：

  10.1016/j.bmc.2004.08.051

文献信息

• Compositions and methods of the use thereof achiral analogues of CC-1065 and the duocarmycins
  申请人：——

  公开号：US20030073731A1

  公开（公告）日：2003-04-17

  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: 1 wherein X is a good leaving group, such as a 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. R 1 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. Examples of the DNA binders are given in Table 4. The preferred DNA binders are groups A, C, D, E, F, G. H and I. R 1 can also include the following: t-butoxy, benzyloxy, 9-fluorenylmethyloxy or other common protecting groups for amines wherein X is a good leaving group, such as a 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. R 1 is a suitable minor groove binding agent to enhance the interactions of the covalently reactive achiral seco-pharmacophore with specific sequences of DNA. Examples of the DNA binders are given in Table 4. The preferred DNA binders are groups A, C, D, E, F, G, H, I, J, K and L. R 2 and R 3 can be hydrogen or short chain alkyl (C1-C5) groups, preferably both being hydrogen atoms. The alkyl groups may be straight chain or branched and include such groups as ethyl, propyl, butyl, pentyl and hexyl. R 4 and R 5 can be hydrogen atoms, short alkyl groups, trifluoromethyl moieties, and alkyloxycarbonyl groups. The preferred R 4 and R 5 groups are methoxycarbonyl and trifluoromethyl. R can be either a benzyl, a benzyloxycarbonyl, a hydrogen atom, a 4-nitrobenzyloxycarbonyl, or a N′-methylpiperazinyl-N-carbonyl group wherein X is a good leaving group, R 1 is a minor groove binding agent, such as the binding units of adozelesin and duocarmycins, netropsin and bisbenzimide. R 2 and R 3 can be hydrogen or short-chain alkyl (C1-C5) groups. R 4 and R 5 can be hydrogen atoms, short alkyl groups, trifluoromethyl moieties, and alkyloxycarbonyl groups. R can be either a benzyl, a benzyloxycarbonyl, a hydrogen atom, a 4-nitrobenzyloxycarbonyl, or a N′-methylpiperazinyl-N-carbonyl group. The present invention is further directed to pharmaceutical compositions thereof, and as a method for treatment of cancer using the subject compounds.

  本发明涉及DNA次要沟槽和序列选择性烷基化剂（+）-CC1065和二聚卡霉素的新型无手性截断类似物，表示为一般的I、II、III、IV和V类：其中X是一个良好的离去基团，例如氯化物、溴化物、碘化物、甲磺酸酯、对甲苯磺酸酯、乙酸酯、季铵盐基团、巯基、烷基亚砜基或烷基砜基，最好是氯化物、溴化物或碘化物基团。R1是适合的次要沟槽结合剂，用于增强无手性截断环丙烯吲哚（CI）或无手性截断二聚卡霉素与DNA特定序列的相互作用。DNA结合剂的示例见表4。首选的DNA结合剂是A、C、D、E、F、G、H和I组。R1还可以包括以下内容：叔丁氧基、苄氧基、9-芴甲氧基或其他常见的胺保护基，其中X是一个良好的离去基团，例如氯化物、溴化物、碘化物、甲磺酸酯、对甲苯磺酸酯、乙酸酯、季铵盐基团、巯基、烷基亚砜基或烷基砜基，最好是氯化物、溴化物或碘化物基团。R1是适合的次要沟槽结合剂，用于增强共价反应性无手性截断药物基团与DNA特定序列的相互作用。DNA结合剂的示例见表4。首选的DNA结合剂是A、C、D、E、F、G、H、I、J、K和L组。R2和R3可以是氢或短链烷基（C1-C5）基团，最好两者都是氢原子。烷基基团可以是直链或支链，并包括乙基、丙基、丁基、戊基和己基等基团。R4和R5可以是氢原子、短烷基基团、三氟甲基基团和烷氧羰基基团。首选的R4和R5基团是甲氧羰基和三氟甲基。R可以是苄基、苄氧羰基、氢原子、4-硝基苄氧羰基或N'-甲基哌嗪基-N-羰基基团，其中X是一个良好的离去基团，R1是一个次要沟槽结合剂，例如阿多泽林和二聚卡霉素、奈曲霉素和双苯并咪啉的结合单元。R2和R3可以是氢或短链烷基（C1-C5）基团。R4和R5可以是氢原子、短烷基基团、三氟甲基基团和烷氧羰基基团。R可以是苄基、苄氧羰基、氢原子、4-硝基苄氧羰基或N'-甲基哌嗪基-N-羰基基团。本发明还涉及其制药组合物，以及使用所述化合物治疗癌症的方法。
• 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.
• A novel class of achiral seco-analogs of CC-1065 and the duocarmycins: design, synthesis, DNA binding, and anticancer properties
  作者：Stanley Kupchinsky、Sara Centioni、Tiffany Howard、John Trzupek、Shane Roller、Virginia Carnahan、Heather Townes、Bethany Purnell、Carly Price、Heather Handl、Kaitlin Summerville、Kimberly Johnson、James Toth、Stephen Hudson、Konstantinos Kiakos、John A. Hartley、Moses Lee

  DOI：10.1016/j.bmc.2004.08.051

  日期：2004.12

  The synthesis, DNA binding properties, and in vitro and in vivo anticancer activity of fifteen achiral seco-cyclopropylindoline (or achiral seco-CI) analogs (5a-o) of CC-1065 and the duocarmycins are described. The achiral seco-CI analogs contain a 4-hydroxyphenethyl halide moiety that is attached to a wide range of indole, benzimidazole, pyrrole, and pyridyl-containing noncovalent binding components

  描述了CC-1065和双carocin的十五种非手性seco-环丙基二氢吲哚啉（或非手性seco-CI）类似物（5a-o）的合成，DNA结合特性以及体外和体内抗癌活性。非手性seco-CI类似物包含4-羟基苯乙基卤化物部分，该部分与各种吲哚，苯并咪唑，吡咯和含吡啶基的非共价结合组分相连。4-羟基苯乙基卤化物部分代表天然产物中存在的癸二环丙基吡咯并吲哚啉（seco-CPI）药效团的最简单模拟物，并且缺少手性中心。使用Taq DNA聚合酶终止测定和使用pBR322或pUC18质粒DNA片段的热诱导DNA切割实验确定了非手性化合物的序列和微小凹槽特异性。例如，seco-CI-InBf（5a）和seco-CI-TMI（5c）显示了对富含AT的序列的特异性，特别是通过与5'-AAAAA（865）-3'的下划线腺嘌呤-N3位置反应。这也是CC-1065和adozelesin偏爱烷基化的顺序。对非手性s