5-(hydroxymethyl)-1-phenylpyrrolidin-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 5-(hydroxymethyl)-1-phenylpyrrolidin-2-one
• 英文别名: (±)-5-(hydroxymethyl)-1-phenylpyrrolidin-2-one；5-(Hydroxymethyl)-1-phenylpyrrolidin-2-one
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: OJRTXCFQOCTOOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(hydroxymethyl)-1-phenylpyrrolidin-2-one 在 sodium hydride 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.5h， 生成 (±)-methyl 2-((5-(allyloxymethyl)-1-phenylpyrrolidin-2-ylidene)amino)-5-methylbenzoate
  参考文献：
  名称：

  Synthesis of C-ring-modified blebbistatin derivatives and evaluation of their myosin II ATPase inhibitory potency

  摘要：

  (S)-Blebbistatin is a micromolar myosin II ATPase inhibitor that is extensively used in research. In search of analogs with improved potency, we have synthesized for the first time C-ring modified analogs. We introduced hydroxymethyl or allyloxymethyl functionalities in search of additional favorable interactions and a more optimal filling of the binding pocket. Unfortunately, the resulting compounds did not significantly inhibit the ATPase activity of rabbit skeletal-muscle myosin II. This and earlier reports suggest that rational design of potent myosin II inhibitors based on the architecture of the blebbistatin binding pocket is an ineffective strategy.

  DOI：

  10.1016/j.bmcl.2018.05.041
• 作为产物：
  描述：

  DL-焦谷氨酸 在 sodium tetrahydroborate 、 氯化亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 72.5h， 生成 5-(hydroxymethyl)-1-phenylpyrrolidin-2-one
  参考文献：
  名称：

  Synthesis of C-ring-modified blebbistatin derivatives and evaluation of their myosin II ATPase inhibitory potency

  摘要：

  (S)-Blebbistatin is a micromolar myosin II ATPase inhibitor that is extensively used in research. In search of analogs with improved potency, we have synthesized for the first time C-ring modified analogs. We introduced hydroxymethyl or allyloxymethyl functionalities in search of additional favorable interactions and a more optimal filling of the binding pocket. Unfortunately, the resulting compounds did not significantly inhibit the ATPase activity of rabbit skeletal-muscle myosin II. This and earlier reports suggest that rational design of potent myosin II inhibitors based on the architecture of the blebbistatin binding pocket is an ineffective strategy.

  DOI：

  10.1016/j.bmcl.2018.05.041

文献信息

• Synthesis of 5-(Hydroxymethyl)pyrrolidin-2-ones by Cyclization of Amide Dianions with Epibromohydrin
  作者：Peter Langer、Ilia Freifeld、Holger Armbrust

  DOI：10.1055/s-2006-942354

  日期：2006.6

  The reaction of amide and thioamide dianions with epibromohydrin resulted in regioselective formation of 5-(hydroxy-methyl)pyrrolidin-2-ones (pyroglutaminols) and -thiones. The cyclization of the dianion of N-(2-tert-butylphenyl)acetamide with epibromohydrin afforded racemic axially chiral 1-(2-tert-butylphenyl)-5-(hydroxymethyl)pyrrolidin-2-one with high diastereoselectivity.

  酰胺和硫代酰胺双阴离子与表溴醇的反应导致区域选择性形成 5-(羟基-甲基)吡咯烷-2-酮 (焦谷氨酰胺) 和 - 硫酮。N-(2-叔丁基苯基)乙酰胺的双阴离子与表溴醇环合得到具有高非对映选择性的外消旋轴向手性1-(2-叔丁基苯基)-5-(羟甲基)吡咯烷-2-酮。
• COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN
  申请人：Global Blood Therapeutics, Inc.

  公开号：US20170174654A1

  公开（公告）日：2017-06-22

  Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

  本文提供的是适用于调节血红蛋白的化合物和药物组合物，它们的制备方法和中间体，以及在治疗由血红蛋白介导的疾病和需要组织和/或细胞氧合的疾病中使用它们的方法。
• Compounds and uses thereof for the modulation of hemoglobin
  申请人：Global Blood Therapeutics, Inc.

  公开号：US10017491B2

  公开（公告）日：2018-07-10

  Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

  本文提供了适合作为血红蛋白调节剂的化合物和药物组合物、制备它们的方法和中间体，以及将它们用于治疗由血红蛋白介导的疾病和可从组织和/或细胞氧合中获益的疾病的方法。
• US9981939B2
  申请人：——

  公开号：US9981939B2

  公开（公告）日：2018-05-29
• Synthesis of C-ring-modified blebbistatin derivatives and evaluation of their myosin II ATPase inhibitory potency
  作者：Bart I. Roman、Sigrid Verhasselt、Christophe W. Mangodt、Olivier De Wever、Christian V. Stevens

  DOI：10.1016/j.bmcl.2018.05.041

  日期：2018.7

  (S)-Blebbistatin is a micromolar myosin II ATPase inhibitor that is extensively used in research. In search of analogs with improved potency, we have synthesized for the first time C-ring modified analogs. We introduced hydroxymethyl or allyloxymethyl functionalities in search of additional favorable interactions and a more optimal filling of the binding pocket. Unfortunately, the resulting compounds did not significantly inhibit the ATPase activity of rabbit skeletal-muscle myosin II. This and earlier reports suggest that rational design of potent myosin II inhibitors based on the architecture of the blebbistatin binding pocket is an ineffective strategy.