8-isopropyl-2(1H)-quinolinone | 165592-47-2

• 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: 8-isopropyl-2(1H)-quinolinone
• 英文别名: 8-isopropylcarbostyril；8-propan-2-yl-1H-quinolin-2-one
• CAS: 165592-47-2
• 化学式: C₁₂H₁₃NO
• 分子量: 187.241
• InChiKey: WMUPNBGULQIPDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  8-isopropyl-2(1H)-quinolinone 在 palladium on activated charcoal 吡啶 、 三氯化铝 、 diethylphosphoryl cyanide 、 氢气 、 三乙胺 作用下， 以 二硫化碳 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 90.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 3,4-dihydro-8-isopropyl-6-(4-(N-methyl-2-phenylethyl)amino-1-piperidinyl)carbonyl-2(1H)-quinolinone
  参考文献：
  名称：

  Novel Selective Hindlimb Vasodilators:  Synthesis and Biological Activity of 1-Acyl-4-aminopiperidine Derivatives

  摘要：

  A series of 6-(4-amino-1-piperidinyl)carbonyl-2(1H)-quinolinones, and their open form derivatives, were synthesized and evaluated for their ability to stimulate femoral artery blood flow (FBF) in the canine hindlimb. All members of this series stimulated FBF, and subsequent experiments revealed that selected members of this series produced minimal changes in coronary blood flow or systemic blood pressure. Compound 25 was the most promising agent in this respect, and clinical trials are now ongoing to evaluate the effectiveness of this drug as a novel treatment for intermittent claudication and Raynaud's phenomenon.

  DOI：

  10.1021/jm020597o
• 作为产物：
  描述：

  2-异丙基苯胺 在 盐酸 、 sodium periodate 、 N-氯代丁二酰亚胺 、 乙醇 、 sodium ethanolate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 10.0h， 生成 8-isopropyl-2(1H)-quinolinone
  参考文献：
  名称：

  Novel Selective Hindlimb Vasodilators:  Synthesis and Biological Activity of 1-Acyl-4-aminopiperidine Derivatives

  摘要：

  A series of 6-(4-amino-1-piperidinyl)carbonyl-2(1H)-quinolinones, and their open form derivatives, were synthesized and evaluated for their ability to stimulate femoral artery blood flow (FBF) in the canine hindlimb. All members of this series stimulated FBF, and subsequent experiments revealed that selected members of this series produced minimal changes in coronary blood flow or systemic blood pressure. Compound 25 was the most promising agent in this respect, and clinical trials are now ongoing to evaluate the effectiveness of this drug as a novel treatment for intermittent claudication and Raynaud's phenomenon.

  DOI：

  10.1021/jm020597o

文献信息

• KRAS G12C INHIBITORS AND METHODS OF USING THE SAME
  申请人：AMGEN INC.

  公开号：US20180177767A1

  公开（公告）日：2018-06-28

  Provided herein are KRAS G12C inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.

  本文提供了KRAS G12C抑制剂，其组成，以及使用方法。这些抑制剂对治疗多种疾病有用，包括胰腺癌、结直肠癌和肺癌。
• Peripheral vasodilators
  申请人：Otsuka Pharmaceutical Co., Ltd.

  公开号：US05591751A1

  公开（公告）日：1997-01-07

  Peripheral vasodilating agents containing, as the active ingredient, carbostyril derivatives represented by the general formula: ##STR1## or a salt thereof; and novel carbostyril derivatives included within the scope of the above-mentioned general formula.

  含有周围血管扩张剂的药物，活性成分为一般式表示的卡波司烯衍生物，或其盐；以及包含在上述一般式范围内的新型卡波司烯衍生物。
• Methods and compositions for inhibition of Ras
  申请人：ARAXES PHARMA LLC

  公开号：US10011600B2

  公开（公告）日：2018-07-03

  Inhibitors of Ras protein, methods to modulate the activity of Ras protein, and methods of treatment of disorders mediated by Ras protein are provided. A method for regulating activity of a K-Ras, H-Ras or N-Ras mutant protein with a compound is described. Disorders that can be treated include cancer, such as hematological cancer, pancreatic cancer, MYH associated polyposis, colorectal cancer, or lung cancer.

  提供了 Ras 蛋白的抑制剂、调节 Ras 蛋白活性的方法以及治疗由 Ras 蛋白介导的疾病的方法。描述了一种用化合物调节 K-Ras、H-Ras 或 N-Ras 突变蛋白活性的方法。可治疗的疾病包括癌症，如血癌、胰腺癌、MYH 相关性息肉病、结直肠癌或肺癌。
• KRAS G12C inhibitors and methods of using the same
  申请人：Amgen Inc.

  公开号：US10519146B2

  公开（公告）日：2019-12-31

  Provided herein are KRAS G12C inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.

  本文提供了 KRAS G12C 抑制剂、其组合物以及使用方法。这些抑制剂可用于治疗多种疾病，包括胰腺癌、结直肠癌和肺癌。
• Substituted cinnolines as inhibitors of KRAS G12C
  申请人：Araxes Pharma LLC

  公开号：US10927125B2

  公开（公告）日：2021-02-23

  Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, tautomer, prodrug or stereoisomer thereof, wherein R1, R2a, R3a, R3b, R4a, R4b, G1, G2, L1, L2, m1, m2, A, B, W, X, Y, Z and E are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.

  本研究提供了具有抑制 G12C 突变 KRAS 蛋白活性的化合物。这些化合物具有以下结构 (I)： 或其药学上可接受的盐、同系物、原药或立体异构体，其中 R1、R2a、R3a、R3b、R4a、R4b、G1、G2、L1、L2、m1、m2、A、B、W、X、Y、Z 和 E 如本文所定义。还提供了与制备和使用此类化合物相关的方法、包含此类化合物的药物组合物以及调节 G12C 突变 KRAS 蛋白活性以治疗疾病（如癌症）的方法。