2-bromothiophene-4-carboxylic acid phenyl ester | 866849-47-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: 2-bromothiophene-4-carboxylic acid phenyl ester
• 英文别名: 5-bromothiophene-3-carboxylic acid phenyl ester；phenyl 2-bromothiophene-4-carboxylate；phenyl 5-bromothiophene-3-carboxylate
• CAS: 866849-47-0
• 化学式: C₁₁H₇BrO₂S
• 分子量: 283.145
• InChiKey: KSUPOQXLCHINQX-UHFFFAOYSA-N

物化性质

• 沸点：
  376.3±27.0 °C(predicted)
• 密度：
  1.586±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-bromothiophene-4-carboxylic acid phenyl ester 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide sodium hydride 、 一水合肼 、 溶剂黄146 、 三乙胺 、 三苯基膦 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 生成 N,N-dimethyl-2-(3-(5-(3-phenoxyprop-1-ynyl)thiophen-3-yl)-1,4-dihydroindeno[1,2-c]pyrazol-6-yloxy)acetamide
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel

  摘要：

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

  DOI：

  10.1021/jm061223o
• 作为产物：
  描述：

  phenyl thiophene-3-carboxylate 在 N-溴代丁二酰亚胺(NBS) 、 溶剂黄146 作用下， 以 乙腈 为溶剂， 以60%的产率得到2-bromothiophene-4-carboxylic acid phenyl ester
  参考文献：
  名称：

  钯催化串联酯舞蹈/脱羰偶联反应

  摘要：

  芳环上的“舞蹈反应”是有机化学中转移芳烃支架上官能团的有效方法。值得注意的是，卤化物和拟卤化物的舞蹈反应在与过渡金属催化的偶联反应结合时，为取代（杂）芳族化合物的不同合成提供了独特的平台。在此，我们报告了由钯催化实现的酯舞和脱羰基偶联的串联反应。在该反应中，芳环上的酯部分发生 1,2-易位后，与亲核试剂发生脱羰偶联，从而能够在起始材料中与酯相邻的位置安装各种亲核试剂。

  DOI：

  10.1021/acs.orglett.2c01432

文献信息

• [EN] TRICYCLIC PYRAZOLE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASES A BASE DE TYRAZOLES TRICYCLIQUES
  申请人：ABBOTT LAB

  公开号：WO2005095387A1

  公开（公告）日：2005-10-13

  Compounds of the present invention are useful for inhibiting protein tyrosine kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  本发明的化合物对抑制蛋白酪氨酸激酶具有用处。还公开了制备这些化合物的方法、含有这些化合物的组合物以及使用这些化合物进行治疗的方法。
• Tricyclic pyrazole kinase inhibitors
  申请人：Arnold D. Lee

  公开号：US20060014816A1

  公开（公告）日：2006-01-19

  Compounds of the present invention are useful for inhibiting protein tyrosine kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  本发明的化合物可用于抑制蛋白酪氨酸激酶。还公开了制备该化合物的方法，含有该化合物的组合物，以及使用该化合物的治疗方法。
• TRICYCLIC PYRAZOLE KINASE INHIBITORS
  申请人：ABBOTT LABORATORIES

  公开号：EP1740579A1

  公开（公告）日：2007-01-10
• US7468371B2
  申请人：——

  公开号：US7468371B2

  公开（公告）日：2008-12-23
• 1,4-Dihydroindeno[1,2-<i>c</i>]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel
  作者：Jürgen Dinges、Daniel H. Albert、Lee D. Arnold、Kimba L. Ashworth、Irini Akritopoulou-Zanze、Peter F. Bousquet、Jennifer J. Bouska、George A. Cunha、Steven K. Davidsen、Gilbert J. Diaz、Stevan W. Djuric、Alan F. Gasiecki、Gary A. Gintant、Vijaya J. Gracias、Christopher M. Harris、Kathryn A. Houseman、Charles W. Hutchins、Eric F. Johnson、Hu Li、Patrick A. Marcotte、Ruth L. Martin、Michael R. Michaelides、Michelle Nyein、Thomas J. Sowin、Zhi Su、Paul H. Tapang、Zhiren Xia、Henry Q. Zhang

  DOI：10.1021/jm061223o

  日期：2007.5.1

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.