2-(4-((3'-amino[3,6'-biquinolin]-4'-yl)amino)phenyl)-2-methyl propanenitrile | 1201646-92-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-(4-((3'-amino[3,6'-biquinolin]-4'-yl)amino)phenyl)-2-methyl propanenitrile
• 英文别名: 2-[4-[(3-Amino-6-quinolin-3-ylquinolin-4-yl)amino]phenyl]-2-methylpropanenitrile
• CAS: 1201646-92-5
• 化学式: C₂₈H₂₃N₅
• 分子量: 429.524
• InChiKey: IUUGABSTPDZAPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  87.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-((3'-amino[3,6'-biquinolin]-4'-yl)amino)phenyl)-2-methyl propanenitrile 、 乙酰氯 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 N-(4'-((4-(2-cyanopropan-2-yl)phenyl)amino)[3,6'-biquinolin]-3'-yl)acetamide
  参考文献：
  名称：

  Novel quinoline-derived mTOR inhibitors with remarkable enzymatic and cellular activities: design, synthesis and biological evaluation

  摘要：

  通过环开放策略获得的化合物24，展现出比最初的引物9更具吸引力的mTOR效力和优越的细胞活性。

  DOI：

  10.1039/c5md00401b
• 作为产物：
  描述：

  4-chloro-6-iodo-3-nitroquinoline 在 四(三苯基膦)钯 、 铁粉 、 potassium carbonate 、 氯化铵 、 溶剂黄146 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 5.25h， 生成 2-(4-((3'-amino[3,6'-biquinolin]-4'-yl)amino)phenyl)-2-methyl propanenitrile
  参考文献：
  名称：

  Establishment of a Structure–Activity Relationship of 1H-Imidazo[4,5-c]quinoline-Based Kinase Inhibitor NVP-BEZ235 as a Lead for African Sleeping Sickness

  摘要：

  Compound NVP-BEZ235 (1) is a potent inhibitor of human phospoinositide-3-kinases and mammalian target of rapamycin (mTOR) that also showed high inhibitory potency against Trypanosoma brucei cultures. With an eye toward using 1 as a starting point for anti-trypanosomal drug discovery, we report efforts to reduce host cell toxicity, to improve the physicochemical properties, and to improve the selectivity profile over human kinases. In this work, we have developed structure-activity relationships for analogues of 1 and have prepared analogues of 1 with improved solubility properties and good predicted central nervous system exposure. In this way, we have identified 4e, 9, 16e, and 16g as the most promising leads to date. We also report cell phenotype and phospholipidomic studies that suggest that these compounds exert their anti-trypanosomal effects, at least in part, by inhibition of lipid kinases.

  DOI：

  10.1021/jm500361r

文献信息

• PHOSPHATIDYLINOSITOL 3 KINASE INHIBITORS
  申请人：QIAN Dapeng

  公开号：US20110212053A1

  公开（公告）日：2011-09-01

  Provided are compounds according to Formula (I): or stereoisomer, prodrug, polymorph, or pharmaceutically acceptable salt forms thereof, wherein X, Y, R 1 , R 6 , R 7 , and R 8 are as defined, and which compounds are effective inhibitors of PI3-kinase and/or other medically and clinically relevant kinases. Also provided are pharmaceutical compositions and methods of using the compounds and compositions as PI3-kinase and kinase inhibitors. More particularly, the compounds of the invention provide treatments and therapeutics for human diseases regulated by, or associated with, the activity of, PI3-kinases and/or protein kinases, or mutant or variant forms thereof.

  提供了以下式子(I)的化合物，或其立体异构体、前药、多晶形或药学上可接受的盐形式，其中X、Y、R1、R6、R7和R8如定义所述，这些化合物是有效的PI3-激酶和/或其他医学和临床相关的激酶抑制剂。还提供了制备这些化合物和组合物作为PI3-激酶和激酶抑制剂的制药组合物和使用方法。更具体地，本发明的化合物为通过PI3-激酶和/或蛋白激酶活性调节或相关联的人类疾病，或其突变或变异形式提供治疗和治疗方法。
• [EN] PHOSPHATIDYLINOSITOL 3 KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PHOSPHATIDYLINOSITOL 3 KINASE
  申请人：PROGENICS PHARM INC

  公开号：WO2009155527A9

  公开（公告）日：2010-05-06
• Establishment of a Structure–Activity Relationship of 1<i>H</i>-Imidazo[4,5-<i>c</i>]quinoline-Based Kinase Inhibitor NVP-BEZ235 as a Lead for African Sleeping Sickness
  作者：João D. Seixas、Sandra A. Luengo-Arratta、Rosario Diaz、Manuel Saldivia、Domingo I. Rojas-Barros、Pilar Manzano、Silvia Gonzalez、Manuela Berlanga、Terry K. Smith、Miguel Navarro、Michael P. Pollastri

  DOI：10.1021/jm500361r

  日期：2014.6.12

  Compound NVP-BEZ235 (1) is a potent inhibitor of human phospoinositide-3-kinases and mammalian target of rapamycin (mTOR) that also showed high inhibitory potency against Trypanosoma brucei cultures. With an eye toward using 1 as a starting point for anti-trypanosomal drug discovery, we report efforts to reduce host cell toxicity, to improve the physicochemical properties, and to improve the selectivity profile over human kinases. In this work, we have developed structure-activity relationships for analogues of 1 and have prepared analogues of 1 with improved solubility properties and good predicted central nervous system exposure. In this way, we have identified 4e, 9, 16e, and 16g as the most promising leads to date. We also report cell phenotype and phospholipidomic studies that suggest that these compounds exert their anti-trypanosomal effects, at least in part, by inhibition of lipid kinases.
• Novel quinoline-derived mTOR inhibitors with remarkable enzymatic and cellular activities: design, synthesis and biological evaluation
  作者：Xiao-Dong Ma、Ni Qiu、Bo Yang、Qiao-Jun He、Yong-Zhou Hu

  DOI：10.1039/c5md00401b

  日期：——

  Compound 24, obtained via a ring-opening strategy, exhibited both attractive mTOR potency and superior cellular activity to initial lead 9.

  通过环开放策略获得的化合物24，展现出比最初的引物9更具吸引力的mTOR效力和优越的细胞活性。