1-(2-Chlorophenyl)octan-1-one | 948296-59-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(2-Chlorophenyl)octan-1-one
• CAS: 948296-59-1
• 化学式: C₁₄H₁₉ClO
• 分子量: 238.757
• InChiKey: OFUUZPCGGYYERJ-UHFFFAOYSA-N

物化性质

• 沸点：
  306.7±15.0 °C(predicted)
• 密度：
  1.029±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  三甲基氰硅烷 、 1-(2-Chlorophenyl)octan-1-one 在 potassium cyanide 、 18-冠醚-6 、 盐酸 作用下， 以 二氯甲烷 、 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 6.75h， 生成 2-(2-chloro-phenyl)-2-hydroxy-nonanoic acid amide
  参考文献：
  名称：

  Block of human NaV1.5 sodium channels by novel α-hydroxyphenylamide analogues of phenytoin

  摘要：

  Voltage-gated sodium (Na) channels are a critical component of electrically excitable cells. Phenytoin (diphenylhydantoin, DPH) is an established sodium channel blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain. In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit human Na(v)1.5 sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells. Phenyl ring substitutions were examined including para-methyl, para-fluoro, para-chloro, ortho-chloro and meta-chloro. We have found that phenyl ring substitutions with electron withdrawing properties resulted in compounds with greater activity. In comparison to diphenylhydantoin, the novel chloro-substituted (alpha-hydroxyphenylamide compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of Na(v)1.5 channels with an IC50 value of 14.5 muM. In addition, the chloro-substitutions have position specific state dependent blocking properties. The ortho-, ineta- and para-chloro substitutions have an 8-, 13- and 3-fold increased affinity for the inactivated state, respectively. Molecular modeling suggests that these differences in affinity are due to a direct interaction with the receptor. Comparing models of diphenylhydantoin to the novel alpha-hydroxyphenlyamide compound suggests that the increased activity may be due to an optimized phenyl ring position and increased molecular volume. This information may be useful in the development of more potent sodium channel blockers. (C) 2004 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2004.01.004
• 作为产物：
  描述：

  邻氯苯腈 、 HEPTYLMAGNESIUM BROMIDE 在 copper(I) bromide 、 硫酸 作用下， 以 乙醚 、 水 为溶剂， 反应 24.5h， 生成 1-(2-Chlorophenyl)octan-1-one
  参考文献：
  名称：

  Block of human NaV1.5 sodium channels by novel α-hydroxyphenylamide analogues of phenytoin

  摘要：

  Voltage-gated sodium (Na) channels are a critical component of electrically excitable cells. Phenytoin (diphenylhydantoin, DPH) is an established sodium channel blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain. In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit human Na(v)1.5 sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells. Phenyl ring substitutions were examined including para-methyl, para-fluoro, para-chloro, ortho-chloro and meta-chloro. We have found that phenyl ring substitutions with electron withdrawing properties resulted in compounds with greater activity. In comparison to diphenylhydantoin, the novel chloro-substituted (alpha-hydroxyphenylamide compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of Na(v)1.5 channels with an IC50 value of 14.5 muM. In addition, the chloro-substitutions have position specific state dependent blocking properties. The ortho-, ineta- and para-chloro substitutions have an 8-, 13- and 3-fold increased affinity for the inactivated state, respectively. Molecular modeling suggests that these differences in affinity are due to a direct interaction with the receptor. Comparing models of diphenylhydantoin to the novel alpha-hydroxyphenlyamide compound suggests that the increased activity may be due to an optimized phenyl ring position and increased molecular volume. This information may be useful in the development of more potent sodium channel blockers. (C) 2004 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejps.2004.01.004

文献信息

• TiCl₄-Catalyzed Indirect Anti-Markovnikov Hydration of Alkynes:  Application to the Synthesis of Benzo[<i>b</i>]furans
  作者：Lutz Ackermann、Ludwig T. Kaspar

  DOI：10.1021/jo070887i

  日期：2007.8.1

  An efficient methodology for the indirect anti-Markovnikov hydration of unsymmetrically substituted terminal and internal alkynes is based on TiCl4-catalyzed hydroamination reactions. Its application to ortho-alkynylhaloarenes, followed by a copper-catalyzed O-arylation, provides flexible access to substituted benzo[b]furans.

  一种不对称取代的末端和内部炔烃的间接反马氏水合的有效方法是基于TiCl 4催化的加氢胺化反应。其在邻炔基卤代芳烃上的应用，然后在铜催化的O-芳基化反应中，可以灵活地获得取代的苯并[ b ]呋喃。
• Block of human NaV1.5 sodium channels by novel α-hydroxyphenylamide analogues of phenytoin
  作者：Paul W. Lenkowski、Seong-Hoon Ko、James D. Anderson、Milton L. Brown、Manoj K. Patel

  DOI：10.1016/j.ejps.2004.01.004

  日期：2004.4

  Voltage-gated sodium (Na) channels are a critical component of electrically excitable cells. Phenytoin (diphenylhydantoin, DPH) is an established sodium channel blocker and is a useful anticonvulsant and class 1b antiarrhythmic, and has been effectively used in the treatment of neuropathic pain. In this study, we have synthesized novel alpha-hydroxyphenylamide analogues of diphenylhydantoin and examined their ability to inhibit human Na(v)1.5 sodium channels expressed in Chinese Hamster Ovary (CHO-K1) cells. Phenyl ring substitutions were examined including para-methyl, para-fluoro, para-chloro, ortho-chloro and meta-chloro. We have found that phenyl ring substitutions with electron withdrawing properties resulted in compounds with greater activity. In comparison to diphenylhydantoin, the novel chloro-substituted (alpha-hydroxyphenylamide compounds produced as much as a 20-fold greater tonic and frequency-dependent blockade of Na(v)1.5 channels with an IC50 value of 14.5 muM. In addition, the chloro-substitutions have position specific state dependent blocking properties. The ortho-, ineta- and para-chloro substitutions have an 8-, 13- and 3-fold increased affinity for the inactivated state, respectively. Molecular modeling suggests that these differences in affinity are due to a direct interaction with the receptor. Comparing models of diphenylhydantoin to the novel alpha-hydroxyphenlyamide compound suggests that the increased activity may be due to an optimized phenyl ring position and increased molecular volume. This information may be useful in the development of more potent sodium channel blockers. (C) 2004 Elsevier B.V. All rights reserved.