2-amino-5-(4-aminophenoxy)-1H-indole-3-carbonitrile | 378236-97-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-amino-5-(4-aminophenoxy)-1H-indole-3-carbonitrile
• 英文别名: 5-(4-aminophenoxy)-2-amino-1H-indole-3-carbonitrile
• CAS: 378236-97-6
• 化学式: C₁₅H₁₂N₄O
• 分子量: 264.286
• InChiKey: LPSILDFVHUZUPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-5-(4-aminophenoxy)-1H-indole-3-carbonitrile 以72%的产率得到5-[4-({N-benzyloxycarbonylalanyl}amino)phenoxy]-2-amino-1H-indole-3-carbonitrile
  参考文献：
  名称：

  Indole derivatives with vascular damaging activity

  摘要：

  该发明提供了一个化合物，其化学式为（I），其中：R1和R2分别选自氢、卤素、—CN、烃基团或化学式（II）的基团；其中W为芳基或杂环基团，R4独立选择自氢、卤素、—OH、氨基、烷酰胺基、—OPO3H2或烃基团，其中氨基团可选择性地被氨基酸残基取代，羟基可选择性酯化，或两个R4基团共同形成一个可选择性取代的环状或杂环基团；X选自$M(y)S+—、+—O—+、—+S(O)+—、—+S(O2)+—和—+NH—；p为0至4之间的整数；q为1至4之间的整数；R3和R10独立选择自氢、较低烷基或化学式（IV）的基团：其中Y选自+NH+—、—$M(Y)O$M(Y)—或键；Z选自+NH+—、—+O&ngr;—、—+C(O)+—或键；r为0至4之间的整数；t为0或1之间的整数；R6为氢、烃基团或化学式（V）的基团：其中n为1至6之间的整数；R7和R8独立选择自氢或烃基团；R11为氢或较低烷基；或其盐或溶剂化合物；但要求：I）当R1为未取代的苯硫基团（Ph—S—）时，R2为H，R10为H且R11为H，则R3既不是H也不是—C(O)—O—CH2CH3；和II）R1、R2和R3不全为氢。预测这类化合物可能导致肿瘤血管的选择性破坏。因此，它们可以用于抑制和/或逆转和/或缓解血管生成及/或与血管生成相关的任何疾病状态的症状。

  公开号：

  US20030216356A1
• 作为产物：
  描述：

  对乙酰氨基酚 在 盐酸 、 sodium hydride 、 溶剂黄146 、 sodium hydroxide 、 sodium nitrite 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 N,N-二甲基乙酰胺 、 水 、 mineral oil 为溶剂， 反应 33.75h， 生成 2-amino-5-(4-aminophenoxy)-1H-indole-3-carbonitrile
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3

  摘要：

  A weak screening hit with suboptimal physicochemical properties was optimized against PFKFB3 kinase using critical structure-guided insights. The resulting compounds demonstrated high selectivity over related PFKFB isoforms and modulation of the target in a cellular context. A selected example demonstrated exposure in animals following oral dosing. Examples from this series may serve as useful probes to understand the emerging biology of this metabolic target.

  DOI：

  10.1021/acs.jmedchem.5b00352

文献信息

• INDOLE DERIVATIVES WITH VASCULAR DAMAGING ACTIVITY
  申请人：AstraZeneca AB

  公开号：EP1289952A1

  公开（公告）日：2003-03-12
• THE USE OF STAR-BRANCHED POLYMERS IN PRESSURE SENSITIVE ADHESIVES
  申请人：National Starch and Chemical Investment Holding Corporation

  公开号：EP1290102A1

  公开（公告）日：2003-03-12
• US6177540B1
  申请人：——

  公开号：US6177540B1

  公开（公告）日：2001-01-23
• US7030123B2
  申请人：——

  公开号：US7030123B2

  公开（公告）日：2006-04-18
• [EN] INDOLE DERIVATIVES WITH VASCULAR DAMAGING ACTIVITY<br/>[FR] DERIVES D'INDOLE POSSEDANT UNE ACTIVITE ENDOMMAGEANT LES VAISSEAUX SANGUINS
  申请人：ASTRAZENECA AB

  公开号：WO2001092224A1

  公开（公告）日：2001-12-06

  The invention provides a compound of Formula (I) wherein: R?1 and R2¿ are independently selected from hydrogen, halogen, -CN, a hydrocarbyl group or a group of Formula (II); wherein W is aryl or a heterocyclic group, R4 is independently selected from hydrogen, halogen, -OH, amino, alkanoylamino, -OPO¿3?H2, or a hydrocarbyl group, wherein the amino group is optionally substituted by an amino acid residue and the hydroxy group is optionally esterified or two R?4¿ groups together form an optionally substituted cyclic or heterocyclic group; X is selected from $M(y) S -, -O- , - S(O) -, - S(O¿2?) - and - NH -; p is an integer from 0 to 4; and q is an integer from 1 to 4; R?3 and R10¿ are independently selected from hydrogen, lower alkyl or a group of Formula (IV): wherein Y is selected from NH -, - $M(Y)O$M(Y)- or a bond; Z is selected from NH -, - Oω-, - C(O) - or a bond; r is an integer from 0 to 4; t is an integer from 0 to 1; R6 is hydrogen, a hydrocarbyl group or a group of Formula (V): wherein n is an integer of from 1 to 6, and; R?7 and R8¿ are independently selected from hydrogen or a hydrocarbyl group; and R11 is hydrogen or lower alkyl; or a salt or solvate thereof; provided that: I) when R1 is an unsubstituted phenylthio group (Ph-S-), R2 is H, R10 is H and R11 is H then R3 is neither H nor- C(O)-O-CH¿2?CH3; and ii) R?1, R2 and R3¿ are not all hydrogen. Such compounds are predicted to cause the selective destruction of tumour vasculature. They may therefore be used to inhibit and/or reverse, and/or alleviate symptoms of angiogenesis and/or any disease state associated with angiogenesis.