methyl 2-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)acetate | 1432910-06-9

• 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: methyl 2-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)acetate
• 英文别名: Methyl 2-[2-chloro-4-(6-methylpyrazin-2-yl)phenyl]acetate；methyl 2-[2-chloro-4-(6-methylpyrazin-2-yl)phenyl]acetate
• CAS: 1432910-06-9
• 化学式: C₁₄H₁₃ClN₂O₂
• 分子量: 276.722
• InChiKey: RUKSDFYJOVUAAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)acetate 在 potassium carbonate 、 三氯氧磷 作用下， 以 甲基萘 、 乙腈 为溶剂， 反应 18.0h， 生成 7-chloro-6-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)-2-(methylthio)pyrido[2,3-d]pyrimidine
  参考文献：
  名称：

  [EN] KINASE INHIBITORS AND USES THEREOF
  [FR] INHIBITEURS DE KINASE ET LEURS UTILISATIONS

  摘要：

  提供了环状亚胺吡啶二烷化合物及其双环衍生物，包括这些化合物的药物组合物，以及使用这些化合物或组合物的方法，例如治疗增殖紊乱疾病的方法，如癌症或肿瘤，或在某些情况下与激酶失调相关的疾病或紊乱，例如但不限于 MAPK、PDGFR、Src、PAKs、c-Kit、EphA2、EphB4、FGFR、Axl 和 c-Met。

  公开号：

  WO2022032071A1
• 作为产物：
  描述：

  2-氯-4-溴苯乙酸 在 盐酸 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 甲苯 为溶剂， 反应 18.0h， 生成 methyl 2-(2-chloro-4-(6-methylpyrazin-2-yl)phenyl)acetate
  参考文献：
  名称：

  An optimized synthesis of the potent and selective Pak1 inhibitor FRAX-1036

  摘要：

  FRAX-1036 is a p21-activated kinase I inhibitor of significant interest to cancer biologists yet no commercial providers or detailed procedures are available. In this Letter, we chronicle the optimized synthesis of FRAX-1036, one of the most specific Paid inhibitors known. We report a 65-fold increase in the overall yield of the seven-step sequence from 0.25% to 16.3%. Our improved route has provided gram quantities of FRAX-1036 for in vivo animal studies by the scientific community. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2015.12.059

文献信息

• SERINE/THREONINE KINASE INHIBITORS
  申请人：GENENTECH, INC.

  公开号：US20150031674A1

  公开（公告）日：2015-01-29

  Compounds having the formula I wherein R 1 , R 2 , R 3 , R 4 , R 5 , R a , R b , R c , R d , R e , n, r, s and t are as defined herein and which compounds are inhibitors of PAK1. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.

  具有公式I的化合物，其中R1、R2、R3、R4、R5、Ra、Rb、Rc、Rd、Re、n、r、s和t的定义如本文所述，并且这些化合物是PAK1的抑制剂。还公开了用于治疗癌症和过度增殖性疾病的组合物和方法。
• PAK INHIBITORS FOR THE TREATMENT OF CELL PROLIFERATIVE DISORDERS
  申请人：AFRAXIS, INC.

  公开号：US20130116263A1

  公开（公告）日：2013-05-09

  Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of cell proliferative disorders and/or CNS disorders.

  本文提供了PAK抑制剂以及利用PAK抑制剂治疗细胞增殖性疾病和/或中枢神经系统疾病的方法。
• [EN] PAK INHIBITORS FOR THE TREATMENT OF CELL PROLIFERATIVE DISORDERS<br/>[FR] INHIBITEURS DE PAK POUR LE TRAITEMENT DE TROUBLES DE PROLIFÉRATION CELLULAIRE
  申请人：AFRAXIS INC

  公开号：WO2013067423A1

  公开（公告）日：2013-05-10

  Provided herein are PAK inhibitors and methods of utilizing PAK inhibitors for the treatment of cell proliferative disorders and/or CNS disorders.

  本文提供PAK抑制剂和利用PAK抑制剂治疗细胞增殖性疾病和/或中枢神经系统疾病的方法。
• Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-p<i>K</i>_a Polar Moiety
  作者：Chudi O. Ndubaku、James J. Crawford、Joy Drobnick、Ignacio Aliagas、David Campbell、Ping Dong、Laura M. Dornan、Sergio Duron、Jennifer Epler、Lewis Gazzard、Christopher E. Heise、Klaus P. Hoeflich、Diana Jakubiak、Hank La、Wendy Lee、Baiwei Lin、Joseph P. Lyssikatos、Jasna Maksimoska、Ronen Marmorstein、Lesley J. Murray、Thomas O’Brien、Angela Oh、Sreemathy Ramaswamy、Weiru Wang、Xianrui Zhao、Yu Zhong、Elizabeth Blackwood、Joachim Rudolph

  DOI：10.1021/acsmedchemlett.5b00398

  日期：2015.12.10

  Signaling pathways intersecting with the p21-activated kinases (PAKs) play important roles in tumorigenesis and cancer progression. By recognizing that the limitations of FRAX1036 (1) were chiefly associated with the highly basic amine it contained, we devised a mitigation strategy to address several issues such as hERG activity. The 5-amino-1,3-dioxanyl moiety was identified as an effective means of reducing pK(a) and logP simultaneously. When positioned properly within the scaffold, this group conferred several benefits including potency, pharmacokinetics, and selectivity. Mouse xenograft PK/PD studies were carried out using an advanced compound, G-5555 (12), derived from this approach. These studies concluded that dose-dependent pathway modulation was achievable and paves the way for further in vivo investigations of PAK1 function in cancer and other diseases.
• [EN] PYRIMIDINE-PYRIDINONE SERINE/THREONINE KINASE INHIBITORS<br/>[FR] INHIBITEURS PYRIMIDINE-PYRIDINONE DE SÉRINE/THRÉONINE KINASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015011252A1

  公开（公告）日：2015-01-29

  Compounds having the formula (I) wherein R1, R2, R3, R4, R5, Ra, Rb, Rc, Rd, Re, n, r, s and t are as defined herein and which compounds are inhibitors of PAKl. Also disclosed are compositions and methods for treating cancer and hyperproliferative disorders.