methyl 2-chloro-6-fluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate | 1357384-85-0

• 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: methyl 2-chloro-6-fluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate
• 英文别名: 2-chloro-3-(Ν-(propylsulfonyl)propylsulfonamido)-6-fluorobenzoic acid methyl ester；Methyl 2-chloro-6-fluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate；methyl 3-[bis(propylsulfonyl)amino]-2-chloro-6-fluorobenzoate
• CAS: 1357384-85-0
• 化学式: C₁₄H₁₉ClFNO₆S₂
• 分子量: 415.891
• InChiKey: WTSUUCRXSCJHSE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  115
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 2-chloro-6-fluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate 在 水 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 16.0h， 以58%的产率得到2-chloro-6-fluoro-3-(propylsulfonamido)benzoic acid
  参考文献：
  名称：

  Pyrazolopyridine inhibitors of B-RafV600E. Part 3: An increase in aqueous solubility via the disruption of crystal packing

  摘要：

  A single crystal was obtained of a lead B-Raf(V600E) inhibitor with low aqueous solubility. The X-ray crystal structure revealed hydrogen-bonded head-to-tail dimers formed by the pyrazolopyridine and sulfonamide groups of a pair of molecules. This observation suggested a medicinal chemistry strategy to disrupt crystal packing and reduce the high crystal lattice energy of alternative inhibitors. Both a bulkier group at the interface of the dimer and an out-of-plane substituent were required to decrease the compound's melting point and increase aqueous solubility. These substituents were selected based on previously developed structure-activity relationships so as to concurrently maintain good enzymatic and cellular activity against B-Raf(V600E). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.030
• 作为产物：
  描述：

  丙基磺酰氯 、 3-氨基-2-氯-6-氟苯甲酸甲酯 生成 methyl 2-chloro-6-fluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate
  参考文献：
  名称：

  KINASE MODULATING COMPOUNDS, COMPOSITIONS CONTAINING THE SAME AND USE THEREOF

  摘要：

  本发明提供了一种由公式（I）所表示的化合物，该化合物可以调节激酶，以及其制备的药物组合物和预防或治疗蛋白激酶介导的疾病或病状的方法。

  公开号：

  US20140296261A1

文献信息

• [EN] KINASE MODULATING COMPOUNDS, COMPOSITIONS CONTAINING THE SAME AND USE THEREOF<br/>[FR] COMPOSÉS MODULANT UNE KINASE, COMPOSITIONS LES CONTENANT ET UTILISATION DE CEUX-CI
  申请人：CENTAURUS BIOPHARMA CO LTD

  公开号：WO2013071865A1

  公开（公告）日：2013-05-23

  The invention provides a compound represented by formula (I) which may modulate a kinase, and a pharmaceutical composition thereof, as well as the method for preventing or treating a protein kinase mediated disease or condition.

  该发明提供了一种由式(I)表示的化合物，可以调节激酶，以及其药物组合物，以及预防或治疗蛋白激酶介导的疾病或病况的方法。
• KINASE MODULATING COMPOUNDS, COMPOSITIONS CONTAINING THE SAME AND USE THEREOF
  申请人：CENTAURUS BIOPHARMA CO., LTD.

  公开号：US20140296261A1

  公开（公告）日：2014-10-02

  The invention provides a compound represented by formula (I) which may modulate a kinase, and a pharmaceutical composition thereof, as well as the method for preventing or treating a protein kinase mediated disease or condition.

  本发明提供了一种由公式（I）所表示的化合物，该化合物可以调节激酶，以及其制备的药物组合物和预防或治疗蛋白激酶介导的疾病或病状的方法。
• US9550781B2
  申请人：——

  公开号：US9550781B2

  公开（公告）日：2017-01-24
• Pyrazolopyridine inhibitors of B-RafV600E. Part 3: An increase in aqueous solubility via the disruption of crystal packing
  作者：Steve Wenglowsky、David Moreno、Joachim Rudolph、Yingqing Ran、Kateri A. Ahrendt、Alisha Arrigo、Ben Colson、Susan L. Gloor、Gregg Hastings

  DOI：10.1016/j.bmcl.2011.12.030

  日期：2012.1

  A single crystal was obtained of a lead B-Raf(V600E) inhibitor with low aqueous solubility. The X-ray crystal structure revealed hydrogen-bonded head-to-tail dimers formed by the pyrazolopyridine and sulfonamide groups of a pair of molecules. This observation suggested a medicinal chemistry strategy to disrupt crystal packing and reduce the high crystal lattice energy of alternative inhibitors. Both a bulkier group at the interface of the dimer and an out-of-plane substituent were required to decrease the compound's melting point and increase aqueous solubility. These substituents were selected based on previously developed structure-activity relationships so as to concurrently maintain good enzymatic and cellular activity against B-Raf(V600E). (C) 2011 Elsevier Ltd. All rights reserved.