1-(2-aminopyrimidin-4-yl)-1H-indole-5-carbonitrile | 1428226-62-3

• 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: 1-(2-aminopyrimidin-4-yl)-1H-indole-5-carbonitrile
• 英文别名: 1-(2-Aminopyrimidin-4-yl)indole-5-carbonitrile；1-(2-aminopyrimidin-4-yl)indole-5-carbonitrile
• CAS: 1428226-62-3
• 化学式: C₁₃H₉N₅
• 分子量: 235.248
• InChiKey: FBOAGQYUFBMKEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-aminopyrimidin-4-yl)-1H-indole-5-carbonitrile 、 N¹-(4-bromo-5-methoxy-2-nitrophenyl)-N¹,N²,N²-trimethylethane-1,2-diamine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 甲苯 为溶剂， 反应 6.0h， 以200 mg的产率得到1-(2-((4-((2-(dimethylamino)ethyl)(methyl)amino)-2-methoxy-5-nitrophenyl)amino)pyrimidin-4-yl)-1H-indole-5-carbonitrile
  参考文献：
  名称：

  EP3345900

  摘要：

  公开号：
• 作为产物：
  描述：

  5-氰基吲哚 、 2-氨基-4-氯嘧啶 以 二甲基亚砜 为溶剂， 生成 1-(2-aminopyrimidin-4-yl)-1H-indole-5-carbonitrile
  参考文献：
  名称：

  N-substituted azaindoles as potent inhibitors of Cdc7 kinase

  摘要：

  Cdc7 kinase is responsible for the initiation and regulation of DNA replication and has been proposed as a target for cancer therapy. We have identified a class of Cdc7 inhibitors based on a substituted indole core. Synthesis of focused indole and azaindole analogs yielded potent and selective 5-azaindole Cdc7 inhibitors with improved intrinsic metabolic stability (ie 36). In parallel, quantum mechanical conformational analysis helped to rationalize SAR observations, led to a proposal of the preferred binding conformation in the absence of co-crystallography data, and allowed the design of 7-azaindole 37 as a second lead in this series. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.02.007

文献信息

• 2, 4-DI-(NITROGEN CONTAINING GROUP) SUBSTITUTED PYRIMIDINE COMPOUND AND PREPARATION METHOD AND USE THEREOF
  申请人：Guangzhou Bebetter Medicine Technology Co., Ltd.

  公开号：EP3345900A1

  公开（公告）日：2018-07-11

  Provided are a 2, 4-di-(nitrogen containing group) substituted pyrimidine compound represented by a general formula (I), a pharmaceutically acceptable salt and a stereoisomer thereof, a preparation method thereof, and a use thereof in preparation of anti-tumor drugs. The compound having a structural feature shown in the general formula (I) can selectively suppress activity of mutant epidermal growth factor receptors (EGFR), including single-mutant EGFR (T790M) and double-mutant EGFR (including L858R/T790M and ex19del/T790M), and can suppress activity of single gain-of-function mutant EGFR (including L858R and ex19del) as well. The compound has a weak suppression effect on wild-type EFGR and a very high selectivity, and thus it has a potential to be used in preparation of drugs for treating EGFR mutant tumors, especially non-small cell lung cancer (NSCLC) comprising a T790M EGFR mutation.

  本发明提供了通式（I）代表的2，4-二（含氮基团）取代的嘧啶化合物、其药学上可接受的盐和立体异构体、其制备方法以及其在制备抗肿瘤药物中的用途。具有通式（I）所示结构特征的化合物可以选择性地抑制突变型表皮生长因子受体（EGFR）的活性，包括单突变型表皮生长因子受体（T790M）和双突变型表皮生长因子受体（包括 L858R/T790M 和 ex19del/T790M），还可以抑制单功能增益突变型表皮生长因子受体（包括 L858R 和 ex19del）的活性。该化合物对野生型 EFGR 的抑制作用较弱，且具有极高的选择性，因此有望用于制备治疗表皮生长因子受体突变肿瘤的药物，尤其是治疗表皮生长因子受体 T790M 突变的非小细胞肺癌（NSCLC）。
• [EN] 2, 4-DI-(NITROGEN CONTAINING GROUP) SUBSTITUTED PYRIMIDINE COMPOUND AND PREPARATION METHOD AND USE THEREOF<br/>[FR] COMPOSÉ PYRIMIDINE À SUBSTITUTION 2,4-DI-(GROUPE AZOTÉ), SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] 2,4-二含氮基团取代嘧啶类化合物及其制备方法和应用
  申请人：GUANGZHOU KEGEN PHARMA CO LTD

  公开号：WO2017036263A1

  公开（公告）日：2017-03-09

  提供一种通式（I）所示的2,4-二含氮基团取代嘧啶类化合物、其药学上可接受的盐或立体异构体，以及其制备方法和在制备肿瘤药物中的用途。该类具有通式（I）结构特征的化合物能够选择性抑制突变型上皮生长因子受体（EGFR）的活性，包括单点突变T790M和双点突变如L858R/T790M，ex19del/T790M，同时对EGFR单点激活突变如L858R和ex19del亦有抑制活性。这类化合物对野生型EGFR抑制作用弱，具有非常高的选择性，有潜力成为用作EGFR突变的恶性肿瘤，尤其是携带T790M EGFR突变的非小细胞肺癌（NSCLC）治疗的药物。
• 2,4-BIS(NITROGEN-CONTAINING GROUP)-SUBSTITUTED PYRIMIDINE COMPOUND, PREPARATION METHOD AND USE THEREOF
  申请人：GUANGZHOU BEBETTER MEDICINE TECHNOLOGY CO., LTD.

  公开号：US20200165227A1

  公开（公告）日：2020-05-28

  Provided are a 2, 4-di-(nitrogen containing group) substituted pyrimidine compound represented by a general formula (I), a pharmaceutically acceptable salt and a stereoisomer thereof, a preparation method thereof, and a use thereof in preparation of anti-tumor drugs. The compound having a structural feature shown in the general formula (I) can selectively suppress activity of mutant epidermal growth factor receptors (EGFR), including single-mutant EGFR (T790M) and double-mutant EGFR (including L858R/T790M and ex19del/T790M), and can suppress activity of single gain-of-function mutant EGFR (including L858R and ex19del) as well. The compound has a weak suppression effect on wild-type EFGR and a very high selectivity, and thus it has a potential to be used in preparation of drugs for treating EGFR mutant tumors, especially non-small cell lung cancer (NSCLC) comprising a T790M EGFR mutation.