(+)-Methylphenyl-phosphoramidat

• 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: (+)-Methylphenyl-phosphoramidat
• 英文别名: [Amino(methoxy)phosphoryl]oxybenzene
• 化学式: C₇H₁₀NO₃P
• 分子量: 187.135
• InChiKey: QWXWDPJTNBTREP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 (+)-Methylphenyl-phosphoramidat
  参考文献：
  名称：

  Optically active alkyl phenyl phosphoramidates: Preparation and stereochemistry of acid-catalyzed alcoholysis.

  摘要：

  甲基（或乙基）苯基氨基磷酸酯（8, 13）的两种对映体均由相应的 L-苯丙氨酸酯（5, 10）的非对映异构体酰胺化物，通过涉及以下顺序的氨基转移反应制备：N-氯化，用甲醇钠处理，以及所得氨基缩醛的温和酸催化水解 (7, 12)。 H+- 和 BF3 催化的 8 和 13 醇解的立体化学研究表明，酸催化剂的性质对反应的空间过程具有深远的影响。在 H+ 催化中观察到的完全立体特异性归因于磷构型反转的直接置换（A-2 机制）。另一方面，同时产生转化（70％）和保留产物（30％）的BF3催化作用是根据（1）用于保留产物形成的五配位中间体机制和（2）双重机制（五配位中间体）来解释的。和直接位移A-2机构，用于反演产物形成。

  DOI：

  10.1248/cpb.27.1641

文献信息

• A reappraisal of the role of the E1cB mechanism of hydrolysis of phosphoramidic derivatives
  作者：Neil K. Hamer、Robert D. Tack

  DOI：10.1039/p29740001184

  日期：——

  lead to the conclusion that, despite considerable differences in rate with varying degree of N-substitution, there is no important contribution from an E1cB process such as operates for related phosphoramidic halides and acyl carbamates. On the basis of the results of studies on the relative rates and direction of cleavage in the basic solvolysis of some OS-dimethyl phosphoramidothioates and phosphoramidodithioates

  已测量了一系列芳基氨基氨基磷酸酯和硫代氨基磷酸酯的碱溶剂分解速率；结果得出的结论是，尽管速率随N取代程度的不同而有很大差异，但E 1cB工艺（例如对相关的磷酰胺卤化物和酰基氨基甲酸酯的操作）并没有重要的贡献。根据对某些OS-二甲基磷酰胺基硫代酸酯和磷酰胺基二硫代酸酯的基本溶剂分解中相对裂解速率和裂解方向的研究结果，与较早的建议相反，有人提出P-O和P-S裂解均主要发生亲核攻击引起的，尽管对后者的某些贡献可能是由消除机制引起的。
• Noncardiotoxic pharmaceutical compounds
  申请人：Barbeau L. Donald

  公开号：US20060035863A1

  公开（公告）日：2006-02-16

  The present invention relates to novel noncardiotoxic compounds and pharmaceutical compositions useful in the treatment of a variety of disorders including the treatment of depression, allergies, psychoses, cancer and gastrointestinal disorders. In particular, the present invention describes pharmaceutical compositions that mitigate life-threatening arrhythmias such as torsade de pointes. Torsade de pointes is a particular cardiac problem associated with many therapeutic agents and has been implicated as a possible cause of sudden death, particularly in those individuals with a past history of disturbances of cardiac rhythm, myocardial infarction, congenital repolarization abnormalities and cardiac risk factors such as hyperlipidemia and age. This arrhythmia is a variant of paroxysmal ventricular tachycardia associated with a prolonged QTc interval or prominent U waves on the ECG. Torsade de pointes is potentially lethal because it can progress to ventricular fibrillation, life-threatening arrhythmias or precipitate sudden death.

  本发明涉及新型无心脏毒性化合物和药物组合物，用于治疗包括抑郁症、过敏、精神病、癌症和胃肠道疾病在内的各种疾病。具体而言，本发明描述了可以缓解危及生命的心律失常，例如扭转型尖波。扭转型尖波是与许多治疗剂相关的一种特殊心脏问题，已被指认为可能导致猝死的原因，特别是在那些有心脏节律紊乱、心肌梗死、先天性复极异常和心脏危险因素（如高脂血症和年龄）的个体中。这种心律失常是一种与心电图上QTc间期延长或U波显著的室性心动过速变异有关的心律失常。扭转型尖波有潜在致命性，因为它可能发展为室颤、危及生命的心律失常或引发猝死。
• NONCARDIOTOXIC PHARMACEUTICAL COMPOUNDS
  申请人：Barbeau, Donald L.

  公开号：EP1778252A2

  公开（公告）日：2007-05-02
• US8088918B2
  申请人：——

  公开号：US8088918B2

  公开（公告）日：2012-01-03
• [EN] NONCARDIOTOXIC PHARMACEUTICAL COMPOUNDS<br/>[FR] COMPOSES PHARMACEUTIQUES NON CARDIOTOXIQUES
  申请人：BARBEAU DONALD L

  公开号：WO2006020573A2

  公开（公告）日：2006-02-23

  The present invention relates to novel noncardiotoxic compounds and pharmaceutical compositions useful in the treatment of a variety of disorders including the treatment of depression, allergies, psychoses, cancer and gastrointestinal disorders. In particular, the present invention describes pharmaceutical compositions that mitigate life-threatening arrhythmias such as torsade de pointes. Torsade de pointes is a particular cardiac problem associated with many therapeutic agents and has been implicated as a possible cause of sudden death, particularly in those individuals with a past history of disturbances of cardiac rhythm, myocardial infarction, congenital repolarization abnormalities and cardiac risk factors such as hyperlipidemia and age. This arrhythmia is a variant of paroxysmal ventricular tachycardia associated with a prolonged QTc interval or prominent U waves on the ECG. Torsade de pointes is potentially lethal because it can progress to ventricular fibrillation, life-threatening arrhythmias or precipitate sudden death.