S-methyl-S-(4-nitrophenyl)-sulfoximine | 1173911-18-6

• 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: S-methyl-S-(4-nitrophenyl)-sulfoximine
• 英文别名: (R)-imino(methyl)(4-nitrophenyl)-λ⁶-sulfanone；Imino-methyl-(4-nitrophenyl)-oxo-lambda6-sulfane；imino-methyl-(4-nitrophenyl)-oxo-λ6-sulfane
• CAS: 1173911-18-6
• 化学式: C₇H₈N₂O₃S
• 分子量: 200.218
• InChiKey: OSHPSKAPWFEQST-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  95.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  大茴香酸 、 S-methyl-S-(4-nitrophenyl)-sulfoximine 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以74 %的产率得到4-methoxy-N-[methyl(4-nitrophenyl)(oxo)-λ⁶-sulfaneylidene]benzamide
  参考文献：
  名称：

  通过空间偏压氮烯转移铁催化硫化物的不对称酰亚胺化

  摘要：

  过渡金属催化的对映选择性氮宾转移到硫化物已成为快速构建对映体富集的硫酰亚胺的最有力的策略之一。然而，与贵金属相比，实现对地球丰富的高活性过渡金属氮烯中间体的立体控制仍然是一个艰巨的挑战。在此，我们公开了使用亚氨基碘烷作为氮宾前体的手性铁(II)/ N , N'-二氧化物催化的二烷基硫醚和烷基芳基硫醚的对映选择性酰亚胺化。以中等至良好的收率和高对映选择性获得了一系列手性磺酰亚胺（56 个实例，收率高达 99%，98:2 er）。通过复杂分子的后期修饰以及手性杀虫剂氟啶虫胺和相关生物活性化合物中间体的合成，证明了该方法的实用性。基于实验研究和理论计算，水键合的高自旋铁氮化物被确定为关键中间体。观察到的立体选择性源于手性洞穴中配体的酰胺单元与硫化物的大取代基之间的空间排斥。此外，二恶唑酮被证明是在铁(III)/ N , N'-二氧化物络合物存在下合适的酰基氮烯前体，导致形成对映选择性反转的硫酰亚

  DOI：

  10.1021/jacs.4c04855
• 作为产物：
  描述：

  1-甲基亚磺酰基-4-硝基苯 在 sodium azide 、 硫酸 作用下， 以 氯仿 、 水 为溶剂， 反应 24.0h， 生成 S-methyl-S-(4-nitrophenyl)-sulfoximine 、 S-methyl-S-(4-nitrophenyl)-sulfoximine
  参考文献：
  名称：

  Sulfoximine-substituted trifluoromethylpyrimidine analogs as inhibitors of proline-rich tyrosine kinase 2 (PYK2) show reduced hERG activity

  摘要：

  The synthesis, in vitro properties, and in vivo pharmacokinetics for a series of sulfoximine-substituted trifluoromethylpyrimidines as inhibitors of proline-rich tyrosine kinase, a target for the possible treatment of osteoporosis, are described. These compounds were prepared as surrogates of the corresponding sulfone compound 1. Sulfone 1 was an attractive PYK2 lead compound; however, subsequent studies determined this compound possessed high dofetilide binding, which is an early indicator of cardiovascular safety. Surprisingly, the corresponding sulfoximine analogs displayed significantly lower dofetilide binding, which, for N-methylsulfoximine (S)-14a, translated to lower activity in a patch clamp hERG K+ ion channel screen. In addition, compound (S)-14a shows good oral exposure in a rat pharmacokinetic model. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.04.093

文献信息

• TANK-BINDING KINASE INHIBITOR COMPOUNDS
  申请人：Gilead Sciences, Inc.

  公开号：US20160096827A1

  公开（公告）日：2016-04-07

  Compounds having the following formula (I) and methods of their use and preparation are disclosed:

  具有以下化学式（I）的化合物以及它们的使用和制备方法已被披露：
• Organocatalytic Kinetic Resolution of Sulfoximines
  作者：Shunxi Dong、Marcus Frings、Hanchao Cheng、Jian Wen、Duo Zhang、Gerhard Raabe、Carsten Bolm

  DOI：10.1021/jacs.6b00143

  日期：2016.2.24

  An efficient kinetic resolution of sulfoximines with enals was realized using chiral N-heterocyclic carbene (NHC) catalysts. The stereoselective amidation proceeds without additional acyl transfer agent. Both enantiomers of the sulfoximines can be obtained with excellent ee values (up to 99% ee and -97% ee, respectively). Performing the catalysis on a gram scale allowed using the recovered sulfoximine

  使用手性 N-杂环卡宾 (NHC) 催化剂实现了亚砜亚胺与烯醛的有效动力学拆分。立体选择性酰胺化无需额外的酰基转移剂即可进行。可以获得具有优异 ee 值的亚砜亚胺的两种对映异构体（分别高达 99% ee 和 -97% ee）。在 FXa 抑制剂 F 的不对称合成中使用回收的亚砜亚胺 (+)-1j 进行克级催化。
• AMINOTRIAZINE DERIVATIVES USEFUL AS TANK-BINDING KINASE INHIBITOR COMPOUNDS
  申请人：Gilead Sciences, Inc.

  公开号：EP3517536A1

  公开（公告）日：2019-07-31

  Compounds having the following formula (I) and methods of their use and preparation are disclosed:(I).

  公开了具有下式(I)的化合物及其使用和制备方法：(I).
• Tank-binding kinase inhibitor compounds
  申请人：Gilead Sciences, Inc.

  公开号：US10040781B2

  公开（公告）日：2018-08-07

  Compounds having the following formula (I) and methods of their use and preparation are disclosed:

  公开了具有下式（I）的化合物及其使用和制备方法：
• Sulfoximine-substituted trifluoromethylpyrimidine analogs as inhibitors of proline-rich tyrosine kinase 2 (PYK2) show reduced hERG activity
  作者：Daniel P. Walker、Michael P. Zawistoski、Molly A. McGlynn、Jian-Cheng Li、Daniel W. Kung、Peter C. Bonnette、Amy Baumann、Leonard Buckbinder、Janet A. Houser、Jason Boer、Anil Mistry、Seungil Han、Li Xing and Angel Guzman-Perez

  DOI：10.1016/j.bmcl.2009.04.093

  日期：2009.6

  The synthesis, in vitro properties, and in vivo pharmacokinetics for a series of sulfoximine-substituted trifluoromethylpyrimidines as inhibitors of proline-rich tyrosine kinase, a target for the possible treatment of osteoporosis, are described. These compounds were prepared as surrogates of the corresponding sulfone compound 1. Sulfone 1 was an attractive PYK2 lead compound; however, subsequent studies determined this compound possessed high dofetilide binding, which is an early indicator of cardiovascular safety. Surprisingly, the corresponding sulfoximine analogs displayed significantly lower dofetilide binding, which, for N-methylsulfoximine (S)-14a, translated to lower activity in a patch clamp hERG K+ ion channel screen. In addition, compound (S)-14a shows good oral exposure in a rat pharmacokinetic model. (C) 2009 Elsevier Ltd. All rights reserved.