5-[(1-苯并呋喃-2-基羰基)氨基]-1H-吲哚-2-羧酸 | 110314-42-6

• 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
• 中文名称: 5-[(1-苯并呋喃-2-基羰基)氨基]-1H-吲哚-2-羧酸
• 英文名称: 5-(benzofuran-2-carboxamido)indole-2-carboxylic acid
• 英文别名: 5-(benzofuran-2-ylcarbonyl)amino-1H-indole-2-carboxylic acid；1H-Indole-2-carboxylic acid, 5-[(2-benzofuranylcarbonyl)amino]-；5-(1-benzofuran-2-carbonylamino)-1H-indole-2-carboxylic acid
• CAS: 110314-42-6
• 化学式: C₁₈H₁₂N₂O₄
• 分子量: 320.304
• InChiKey: BYSRZPAQWYCFMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  95.3
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  5-[(1-苯并呋喃-2-基羰基)氨基]-1H-吲哚-2-羧酸 在 palladium on activated charcoal 吡啶 、 甲酸铵 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 红铝 、 lithium chloride 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 adozelesin
  参考文献：
  名称：

  Coupling of cyclopropapyrroloindole (CPI) derivatives. The preparation of CC-1065, ent-CC-1065, and analogs

  摘要：

  DOI：

  10.1021/ja00256a041
• 作为产物：
  描述：

  ethyl 5-(1-benzofuran-2-carbonylamino)-1H-indole-2-carboxylate 以80%的产率得到
  参考文献：
  名称：

  WARPEHOSKI, M. A.;GEBHARD, I.;KELLY, R. C.;KRUEGER, W. C.;LI, L. H.;MCGOV+, J. MED. CHEM., 31,(1988) N 3, 590-603

  摘要：

  DOI：

文献信息

• 5-Amino-1-(chloromethyl)-1,2-dihydro-3<i>H</i>-benz[<i>e</i>]indoles:  Relationships between Structure and Cytotoxicity for Analogues Bearing Different DNA Minor Groove Binding Subunits
  作者：Graham J. Atwell、Jared J. B. Milbank、William R. Wilson、Alison Hogg、William A. Denny

  DOI：10.1021/jm990136b

  日期：1999.8.1

  relationships for the cytotoxicity of side chain analogues. Compounds were prepared by coupling 1-(chloromethyl)-5-nitro-1, 2-dihydro-3H-benz[e]indole to appropriate carboxylic acids, followed by nitro group reduction, or by coupling suitable 5-amino-protected indolines to alpha,beta-unsaturated acids, followed by deblocking. These AT-specific DNA alkylating agents were evaluated for cytotoxicity in a series

  制备了一系列5-氨基-seco-CBI化合物，设计用作前药的效应子，以研究结构-活性关系对侧链类似物的细胞毒性。通过将1-（氯甲基）-5-硝基-1，2-二氢-3H-苯并[e]吲哚与合适的羧酸偶联，然后进行硝基还原，或通过将合适的5-氨基保护的二氢吲哚偶联至化合物来制备化合物。 α，β-不饱和酸，然后脱保护。在一系列肿瘤细胞系（AA8，UV4，EMT6，SKOV3）中评估了这些AT特异的DNA烷基化剂的细胞毒性。对于那些带有吲哚羰基侧链的类似物，5'-甲氧基衍生物具有最高的细胞毒性（AA8细胞中IC（50）1.3 nM，暴露4 h），与亲本CBI-TMI（5'，6' ，7'-三甲氧基吲哚）衍生物（IC（50）0。在上述测定中为46 nM）。带有O（CH（2））（2）NMe（2）取代基的增溶衍生物的子集的效力降低了约10倍。对于在侧链中含有丙烯酰基接头的化合物，证明4'-甲氧基肉桂酰基衍生物具
• Conjugates between minor groove binders and Zn(II)-tach complexes: Synthesis, characterization, and interaction with plasmid DNA
  作者：Claudia Sissi、Luca Dovigo、Maria Laura Greco、Antonella Ciancetta、Stefano Moro、Jakub W. Trzciński、Fabrizio Mancin、Paola Rossi、Giampiero Spalluto、Paolo Tecilla

  DOI：10.1016/j.tet.2017.04.013

  日期：2017.5

  of conjugates between a Zn(II)-tach complex and (indole)2 or benzofuran-indole amide minor groove binders connected through alkyl or oxyethyl linkers of different lengths has been prepared. The conjugates bind strongly to DNA. However, the complexation to DNA to promote the Zn(II) catalyzed hydrolytic cleavage of the DNA results instead in its inhibition. This inhibition effect has been confirmed also

  Zn（II）-tach络合物和（吲哚）2之间的新的共轭物家族已经制备了通过不同长度的烷基或氧乙基接头连接的苯并呋喃-吲哚酰胺或苯并呋喃-吲哚酰胺小沟粘合剂。结合物与DNA牢固结合。但是，与DNA的络合促进了Zn（II）催化的DNA的水解裂解，反而导致了对DNA的抑制。使用Cu（II）也已经证实了这种抑制作用。建模研究表明，在最稳定的复合物构象中，小沟结合剂和接头位于小沟中，阻碍了金属配合物与DNA磷酸盐骨架之间的相互作用。因此，小沟槽粘合剂-连接剂-金属络合物的线性排列似乎对于确保紧密结合是有效的，但是从水解的观点来看是无效的。
• 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。
• Trifluoromethylpyrroloindolecarboxylic acid ester and process for
  申请人：Kyorin Pharmaceutical Co., Ltd.

  公开号：US05629430A1

  公开（公告）日：1997-05-13

  Trifluoromethylpyrroloindolecarboxylic acid ester derivatives, and optical isomers and pharmaceutically acceptable salts thereof are provided which are represented by the general formula (1): ##STR1## or the general formula (2): ##STR2## The compounds are antineoplastic agents which are selective to cancer cells, effective also to solid cancer, and less toxic.

  提供了三氟甲基吡咯吲哌酮酸酯衍生物，以及它们的光学异构体和药学上可接受的盐，其通式表示为（1）： ##STR1## 或通式（2）： ##STR2## 这些化合物是选择性作用于癌细胞的抗肿瘤剂，对实体癌也有效，并且毒性较小。
• Novel tumor-selective chemotherapeutic agents
  申请人：Wang Yuqiang

  公开号：US20050239864A1

  公开（公告）日：2005-10-27

  The present invention relates to novel CC-1065 derivatives that bind to albumin in vitro and in vivo forming albumin-drug conjugates, and their methods of preparation and use as antitumor agents.

  本发明涉及新型CC-1065衍生物，其在体外和体内与白蛋白结合形成白蛋白-药物结合物，并且它们的制备方法和用作抗肿瘤剂的方法。