2-methyl-N¹-(1-methylpiperidin-4-yl)benzene-1,4-diamine | 955369-23-0

• 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: 2-methyl-N¹-(1-methylpiperidin-4-yl)benzene-1,4-diamine
• 英文别名: 2-methyl-1-N-(1-methylpiperidin-4-yl)benzene-1,4-diamine
• CAS: 955369-23-0
• 化学式: C₁₃H₂₁N₃
• mdl: MFCD12167288
• 分子量: 219.33
• InChiKey: OWQBMWLTEDIMIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.538
• 拓扑面积：
  41.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-methyl-N¹-(1-methylpiperidin-4-yl)benzene-1,4-diamine 、 (R)-1-(2-bromopyridin-4-yl)-N-(4-(trifluoromethoxy)benzyl)piperidine-3-carboxamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以57%的产率得到(R)-1-(2-((3-methyl-4-((1-methylpiperidin-4-yl)amino)phenyl)amino)pyridin-4-yl)-N-(4-(trifluoromethoxy)benzyl)piperidine-3-carboxamide
  参考文献：
  名称：

  设计，合成和生物评价2-氨基-4-（1-哌啶）吡啶衍生物作为新型抗克唑替尼耐药ALK / ROS1双重抑制剂

  摘要：

  自从克唑替尼被临床用于治疗非小细胞肺癌以来，ALK和ROS1激酶已成为有希望的治疗靶标。为了探索新的有效抑制剂，在铅化合物A的基础上设计并合成了一系列2-氨基-4-（1-哌啶）吡啶衍生物，这些衍生物在ALK激酶域中稳定了新的DFG移位构象。评估强调，这些新化合物中的大多数也可以有效抑制ROS1激酶，从而成为有前景的针对ROS1和ALK的抑制剂。其中，代表性化合物2e对ALK上瘾的H3122和ROS1上瘾的HCC78细胞系（IC 50 分别为6.27μM和10.71μM）具有很强的抗增殖活性，与克唑替尼相当。而且2e对临床上耐克唑替尼的ALK L1196M表现出令人印象深刻的酶活性，IC 50值为41.3 nM，比克唑替尼的效价高约2倍。2e还显示出在含有ROS1 G2032R的Ba / F3细胞系中强效抑制活性比克唑替尼高约6倍（IC 50：104.7 nM对643.5 nM）。此外，分子

  DOI：

  10.1016/j.ejmech.2019.06.043

文献信息

• Dihydropyrazolopyrimidinone derivatives
  申请人：Sagara Takeshi

  公开号：US20070254892A1

  公开（公告）日：2007-11-01

  The invention relates to compounds of a general formula (I): wherein Ar 1 is an optionally-substituted aryl or heteroaromatic group; R 1 is an optionally-substituted lower alkyl, lower alkenyl, lower alkynyl or cyclo-lower alkyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R 2 is a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R 3 is a hydrogen atom or a lower alkyl group; R 4 is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a group of —N(R 1k )R 1m ; T and U are a nitrogen atom or a methine group, etc. The compounds of the invention have excellent Weel kinase-inhibitory effect and are therefore useful in the field of medicines, especially treatment of various cancers.

  该发明涉及一般式（I）的化合物，其中Ar1是可选择取代的芳基或杂环芳基；R1是可选择取代的较低烷基、较低烯烃基、较低炔烃基或环状较低烷基基团，或是具有取代基的芳基、芳基烷基或杂环芳基；R2是氢原子、较低烷基基团、较低烯烃基团或较低炔烃基团，或是具有取代基的芳基、芳基烷基或杂环芳基；R3是氢原子或较低烷基基团；R4是氢原子、卤素原子、羟基、较低烷基基团或—N(R1k)R1m基团；T和U是氮原子或亚甲基基团等。该发明的化合物具有出色的Weel激酶抑制作用，因此在药物领域中特别适用于治疗各种癌症。
• [EN] SUBSTITUTED N-PHENYLPYRIMIDIN-2-AMINE ANALOGS AS INHIBITORS OF THE AXL KINASE<br/>[FR] ANALOGUES DE N-PHÉNYLPYRIMIDINE-2-AMINE SUBSTITUÉS EN TANT QU'INHIBITEURS DE L'AXL KINASE
  申请人：UNIV UTAH RES FOUND

  公开号：WO2012135800A1

  公开（公告）日：2012-10-04

  In one aspect, the invention relates to substituted N-phenylpyrimidin-2-amine analogs, derivatives thereof, and related compounds, which are useful as inhibitors of Axl kinase; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of using the compounds and compositions for treating disorders associated with dysfunction of the Axl kinase. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  该发明涉及替代的N-苯基嘧啶-2-胺类似物、其衍生物和相关化合物，它们可作为Axl激酶的抑制剂；合成这些化合物的方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与Axl激酶功能障碍相关的疾病的方法。本文摘要旨在作为在特定领域搜索的工具，并不意味着对本发明的限制。
• DIHYDROPYRAZOLOPYRIMIDINONE DERIVATIVES
  申请人：Sagara Takeshi

  公开号：US20110189130A1

  公开（公告）日：2011-08-04

  The invention relates to compounds of a general formula (I): wherein Ar 1 is an optionally-substituted aryl or heteroaromatic group; R 1 is an optionally-substituted lower alkyl, lower alkenyl, lower alkynyl or cyclo-lower alkyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R 2 is a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R 3 is a hydrogen atom or a lower alkyl group; R 4 is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a group of —N(R 1k )R 1m ; T and U are a nitrogen atom or a methine group, etc. The compounds of the invention have excellent Weel kinase-inhibitory effect and are therefore useful in the field of medicines, especially treatment of various cancers.

  本发明涉及一般式(I)的化合物：其中Ar1是可选取代的芳基或杂环芳基基团；R1是可选取代的低碳基、低烯基、低炔基或环-低碳基基团，或是带有取代基的芳基、芳基烷基或杂环芳基基团；R2是氢原子、低碳基、低烯基或低炔基，或是带有取代基的芳基、芳基烷基或杂环芳基基团；R3是氢原子或低碳基；R4是氢原子、卤素原子、羟基、低碳基或—N(R1k)R1m基团；T和U是氮原子或甲基基团等。该发明的化合物具有出色的Weel激酶抑制作用，因此在药物领域，特别是治疗各种癌症方面非常有用。
• Dihydropyrazolopyrimidinone Derivatives
  申请人：Sakamoto Toshihiro

  公开号：US20100063024A1

  公开（公告）日：2010-03-11

  The invention relates to compounds of a general formula (I): wherein Ar 1 is an optionally-substituted aryl or heteroaromatic group; R 1 is an optionally-substituted lower alkyl, lower alkenyl, lower alkynyl or cyclo-lower alkyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R 2 is a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group, or is an aryl, aralkyl or heteroaromatic group optionally having a substituent; R 3 is a hydrogen atom or a lower alkyl group; R 4 is a hydrogen atom, a halogen atom, a hydroxyl group, a lower alkyl group or a group of —N(R 1k )R 1m ; T and U are a nitrogen atom or a methine group, etc. The compounds of the invention have excellent Weel kinase-inhibitory effect and are therefore useful in the field of medicines, especially treatment of various cancers.

  本发明涉及一般式（I）的化合物：其中Ar1是可选取取代基的芳基或杂环芳基基团；R1是可选取取代基的低碳基、低烯基、低炔基或环低碳基基团，或是带取代基的芳基、芳基烷基或杂环芳基基团；R2是氢原子、低碳基、低烯基或低炔基，或是带取代基的芳基、芳基烷基或杂环芳基基团；R3是氢原子或低碳基；R4是氢原子、卤素原子、羟基、低碳基或-N（R1k）R1m基团；T和U是氮原子或甲基烷基等。本发明的化合物具有出色的Weel激酶抑制作用，因此在药物领域中特别适用于治疗各种癌症。
• COMPOUNDS FOR TREATING NEUROPSYCHIATRIC CONDITIONS
  申请人：Campbell David

  公开号：US20120046283A1

  公开（公告）日：2012-02-23

  Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of neuropsychiatric conditions.

  本文提供了PAK抑制剂及其在治疗神经精神疾病方面的应用方法。