(2-bromo-5-fluorophenyl)(4-methoxyphenyl)methanone

• 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: (2-bromo-5-fluorophenyl)(4-methoxyphenyl)methanone
• 英文别名: (2-Bromo-5-fluorophenyl)-(4-methoxyphenyl)methanone
• 化学式: C₁₄H₁₀BrFO₂
• mdl: MFCD11545177
• 分子量: 309.135
• InChiKey: PSZWPCNISLYFOT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2-bromo-5-fluorophenyl)(4-methoxyphenyl)methanone 在 aluminum (III) chloride 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以56%的产率得到(2-bromo-5-fluorophenyl)(4-hydroxyphenyl)methanone
  参考文献：
  名称：

  Synthesis and biological evaluation of negative allosteric modulators of the Kv11.1(hERG) channel

  摘要：

  We synthesized and evaluated a series of compounds for their allosteric modulation at the K(v)11.1 (hERG) channel. Most compounds were negative allosteric modulators of [H-3]dofetilide binding to the channel, in particular 7f, 7h-j and 7p. Compounds 7f and 7p were the most potent negative allosteric modulators amongst all ligands, significantly increasing the dissociation rate of dofetilide in the radioligand kinetic binding assay, while remarkably reducing the affinities of dofetilide and astemizole in a competitive displacement assay. Additionally, both 7f and 7p displayed peculiar displacement characteristics with Hill coefficients significantly distinct from unity as shown by e.g., dofetilide, further indicative of their allosteric effects on dofetilide binding. Our findings in this investigation yielded several promising negative allosteric modulators for future functional and clinical research with respect to their antiarrhythmic propensities, either alone or in combination with known K(v)11.1 blockers. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.032
• 作为产物：
  描述：

  2-溴-5-氟苯甲酸 在 aluminum (III) chloride 、 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 生成 (2-bromo-5-fluorophenyl)(4-methoxyphenyl)methanone
  参考文献：
  名称：

  Synthesis and biological evaluation of negative allosteric modulators of the Kv11.1(hERG) channel

  摘要：

  We synthesized and evaluated a series of compounds for their allosteric modulation at the K(v)11.1 (hERG) channel. Most compounds were negative allosteric modulators of [H-3]dofetilide binding to the channel, in particular 7f, 7h-j and 7p. Compounds 7f and 7p were the most potent negative allosteric modulators amongst all ligands, significantly increasing the dissociation rate of dofetilide in the radioligand kinetic binding assay, while remarkably reducing the affinities of dofetilide and astemizole in a competitive displacement assay. Additionally, both 7f and 7p displayed peculiar displacement characteristics with Hill coefficients significantly distinct from unity as shown by e.g., dofetilide, further indicative of their allosteric effects on dofetilide binding. Our findings in this investigation yielded several promising negative allosteric modulators for future functional and clinical research with respect to their antiarrhythmic propensities, either alone or in combination with known K(v)11.1 blockers. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.10.032

文献信息

• Highly Enantioselective Synthesis of Chiral Benzhydrols via Manganese Catalyzed Asymmetric Hydrogenation of Unsymmetrical Benzophenones Using an Imidazole-Based Chiral PNN Tridentate Ligand
  作者：Fei Ling、Huacui Hou、Jiachen Chen、Sanfei Nian、Xiao Yi、Ze Wang、Dingguo Song、Weihui Zhong

  DOI：10.1021/acs.orglett.9b01056

  日期：2019.6.7

  A series of Mn(I) catalysts containing imidazole-based chiral PNN tridentate ligands with controllable “side arm” groups have been established, enabling the asymmetrical hydrogenation of unsymmetrical benzophenones with outstanding activity (up to 13 000 TON) and excellent enantioselectivity (up to >99% ee). This protocol uses K2CO3 as an industrially desirable base and features a wide substrate scope

  已经建立了一系列含有咪唑基手性PNN三齿配体和可控“侧臂”基团的Mn（I）催化剂，能够使不对称二苯甲酮进行不对称氢化，具有出色的活性（高达13000吨）和出色的对映选择性（高达> 99％ee）。该协议使用K 2 CO 3作为工业上可取的碱，并且具有广泛的底物范围和官能团耐受性。此外，催化剂中的亚胺基对于获得高活性和良好的对映选择性至关重要。
• Neue asymmetrische, halogenierte Benzophenone und Verfahren zu ihrer Herstellung
  申请人：HOECHST AKTIENGESELLSCHAFT

  公开号：EP0600318A1

  公开（公告）日：1994-06-08

  Verbindungen der Formel worin R¹ bis R⁵ Wasserstoff-, Fluor-, Chlor- oder Bromatome bedeuten, wobei mindestens einer der Substituenten R¹ - R⁵ kein Wasserstoffatom darstellt, R⁶ bis R¹⁰ Wasserstoff-, Fluor-, Chlor- oder Bromatome, Nitro-, Alkyl(C₁-C₄)-, Alkoxy (C₁-C₄)-grupppen oder ggfs. substituierte Phenyl- oder Naphthylgruppen bedeuten, wobei bis zu 3 der Substituenten R⁶ - R¹⁰ Alkyl(C₁-C₄)-, Alkoxy-(C₁-C₄)- oder die genannten Arylgruppen und höchstens einer der Substituenten R⁶ - R¹⁰ eine Nitrogruppe darstellen können, und wobei die Zahl der Halogenatome und Nitrogruppen von R⁶ - R¹⁰, vermindert um die Zahl der Alkyl(C₁-C₄)-, Alkoxy-(C₁-C₄)- und Arylgruppen von R⁶ - R¹⁰, um mindestens 1 geringer ist als die Zahl der Halogenatome von R¹ bis R⁵, und Verfahren zu ihrer Herstellung, indem man entsprechende halogenierte Benzole mit entsprechenden substituierten Benzoylhalogeniden in Gegenwart eines Katalysators bei 0° bis 230°C acyliert und die erhaltenen Benzophenone ggfs. bei 120°C bis 280°C mit KF, RbF oder CsF umsetzt (fluoriert).

  式中的化合物 其中 R¹ 至 R⁵ 为氢、氟、氯或溴原子，取代基 R¹ - R⁵ 中至少有一个不是氢原子、R⁶至 R¹⁰ 为氢、氟、氯或溴原子、硝基、烷基（C₁-C₄）、烷氧基（C₁-C₄）基团或（如适当）取代苯基或萘基。取代苯基或萘基，其中最多 3 个取代基为 R⁶ - R¹⁰ 烷基（C₁-C₄）-、烷氧基-(C₁-C₄)-或上述芳基，取代基R⁶ - R¹⁰中最多有一个可以代表硝基，其中R⁶ - R¹⁰的卤素原子和硝基的数目减去烷基-(C₁-C₄)-的数目、R⁶-R¹⁰的烷氧基(C₁-C₄)和芳基的数目至少比R¹至R⁵的卤原子数目少1个，以及它们的制备工艺：在催化剂存在下，在0°至230°C下用相应的取代苯甲酰基卤酰化相应的卤代苯，并酌情在120°C至280°C下用K-乙酰胺反应所得的二苯甲酮。在 120°C 至 280°C 下与 KF、RbF 或 CsF 反应（氟化）。
• Synthesis and biological evaluation of negative allosteric modulators of the Kv11.1(hERG) channel
  作者：Zhiyi Yu、Jacobus P.D. van Veldhoven、Ingrid M.E. 't Hart、Adrian H. Kopf、Laura H. Heitman、Adriaan P. IJzerman

  DOI：10.1016/j.ejmech.2015.10.032

  日期：2015.12

  We synthesized and evaluated a series of compounds for their allosteric modulation at the K(v)11.1 (hERG) channel. Most compounds were negative allosteric modulators of [H-3]dofetilide binding to the channel, in particular 7f, 7h-j and 7p. Compounds 7f and 7p were the most potent negative allosteric modulators amongst all ligands, significantly increasing the dissociation rate of dofetilide in the radioligand kinetic binding assay, while remarkably reducing the affinities of dofetilide and astemizole in a competitive displacement assay. Additionally, both 7f and 7p displayed peculiar displacement characteristics with Hill coefficients significantly distinct from unity as shown by e.g., dofetilide, further indicative of their allosteric effects on dofetilide binding. Our findings in this investigation yielded several promising negative allosteric modulators for future functional and clinical research with respect to their antiarrhythmic propensities, either alone or in combination with known K(v)11.1 blockers. (C) 2015 Elsevier Masson SAS. All rights reserved.