[2H4]-塞来昔布 | 544686-20-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: [2H4]-塞来昔布
• 英文名称: 2,3,5,6-tetradeutero-4-[5-(4-methylbenzenyl)-3-trifluoromethyl-pyrazol-1-yl]benzenesulfonamide
• 英文别名: 2,3,5,6-tetradeutero-4-[5-(4-tolyl)-3-trifluoromethylpyrazol-1-yl]benzenesulfonamide；Tetradeutero-4-[5-(4-tolyl)-3-trifluoromethyl-pyrazol-1-yl]benzenesulfonamide；Celecoxib-d4；2,3,5,6-tetradeuterio-4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
• CAS: 544686-20-6
• 化学式: C₁₇H₁₄F₃N₃O₂S
• 分子量: 385.347
• InChiKey: RZEKVGVHFLEQIL-YKVCKAMESA-N

物化性质

• 熔点：
  157-159°C
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  86.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  塞来西布 在 氘 作用下， 生成 [2H4]-塞来昔布
  参考文献：
  名称：

  温度介导的氢同位素交换反应中铱（I）催化剂的比较。

  摘要：

  铱（I）催化的氢同位素交换（HIE）反应的反应性和选择性可以通过使用宽范围的反应温度来改变。在这里，我们已经做了与普通铱（I）催化剂（详细的比较研究1 - 6），这将有助于我们理解和优化方法无论是高选择性或最大的氘引入的。我们已经证明，这些研究的铱（I）催化剂的温度窗口令人惊讶地非常宽。这一原理在复杂药物分子的某些HIE反应中得到了进一步证明。

  DOI：

  10.1002/open.201900204

文献信息

• The Synthesis of Highly Active Iridium(I) Complexes and their Application in Catalytic Hydrogen Isotope Exchange
  作者：Jack A. Brown、Alison R. Cochrane、Stephanie Irvine、William J. Kerr、Bhaskar Mondal、John A. Parkinson、Laura C. Paterson、Marc Reid、Tell Tuttle、Shalini Andersson、Göran N. Nilsson

  DOI：10.1002/adsc.201400730

  日期：2014.11.24

  AbstractA series of robust iridium(I) complexes bearing a sterically encumbered N‐heterocyclic carbene ligand, alongside a phosphine ligand, has been synthesised and investigated in hydrogen isotope exchange processes. These complexes have allowed isotope incorporation over a range of substrates with the use of practically convenient deuterium and tritium gas. Moreover, these active catalysts are capable of isotope incorporation to particularly high levels, whilst employing low catalyst loadings and in short reaction times. In addition to this, these new catalyst species have shown flexible levels of chemoselectivity, which can be altered by simple manipulation of preparative approaches. Furthermore, a number of industrially‐relevant drug molecules has also been labelled, including the sulfonamide containing drug, Celecoxib. Alongside detailed NMR experiments, initial mechanistic investigations have also been performed, providing insight into both substrate binding energies, and, more importantly, relative energies of key steps in the mechanistic cycle as part of the overall exchange process.magnified image
• Iridium-Catalyzed C–H Activation and Deuteration of Primary Sulfonamides: An Experimental and Computational Study
  作者：William J. Kerr、Marc Reid、Tell Tuttle

  DOI：10.1021/cs5015755

  日期：2015.1.2

  Iridium-catalyzed C-H activation and ortho-hydrogen isotope exchange is an important technology for allowing access to labelled organic substrates and aromatic drug molecules, and for the development of further C-H activation processes in organic synthesis. The use of [(COD)Ir(NHC)Cl] complexes (NHC = N-heterocyclic carbene) in the ortho-deuteration of primary sulfonamides under ambient conditions is reported. This methodology has been applied to the deuteration of a series of substrates, including the COX-2 inhibitors Celecoxib and Mavacoxib, demonstrating selective complexation of the primary sulfonamide over a competing pyrazole moiety. The observed chemoselectivity can be reversed by employing more encumbered catalyst derivatives of the type [(COD)Ir(NHC)(PPh3)]PF6. Computational studies have revealed that, although C-H activation is rate-determining, substrate complexation or subsequent C-H activation can be product-determining depending on the catalyst employed.
• DEUTERIERTE SUBSTITUIERTE PYRAZOLYL-BENZOLSULFONAMIDE SOWIE DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL
  申请人：Turicum Drug Development AG

  公开号：EP1456179A1

  公开（公告）日：2004-09-15
• [DE] DEUTERIERTE SUBSTITUIERTE PYRAZOLYL-BENZOLSULFONAMIDE SOWIE DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL<br/>[EN] DEUTERATED SUBSTITUTED PYRAZOLYLBENZYLSULFONAMIDES AND MEDICAMENTS COMPRISING SAID COMPOUNDS<br/>[FR] PYRAZOLYL-BENZOLSULFONAMIDES SUBSTITUES DEUTERIES ET MEDICAMENTS CONTENANT CES COMPOSES
  申请人：BEROLINA DRUG DEV AB

  公开号：WO2003050091A1

  公开（公告）日：2003-06-19

  Die Erfindung betrifft deuterierte substituierte Pyrazolyl-Benzolsulfonamide sowie diese Verbindungen enthaltende Arzneimittel sowie diese Verbindungen enthaltende Arzneimittel. Weiterhin betrifft die Erfindung die Verwendung deuterierter substituierter Pyrazolyl-Benzolsulfonamide zur symptomatischen Behandlung von Osteoarthritis und rheumatoider Arthritis sowie zur Verhinderung und Behandlung von Neoplasie insbesondere adenomatöser colorektaler Polypen bei familiärer adenomatöser Polyposis, zur Behandlung von Schmerzen, inbesondere akute Schmerzen, und Dysmenorrhoe, insbesondere primäre Dysmenorrhoe. Ausserdem offenbart die Erfindung pharmazeutische Zusammensetzungen, welche deuterierte substituierte Pyrazolyl-Benzolsulfonamide sowie deren physiologisch verträgliche Salze, neben pharmazeutisch verträglichen Hilfs- und/oder Zusatzstoffen, zur symptomatischen Behandlung von Osteoarthritis und rheumatoider Arthritis sowie zur Verhinderung und Behandlung von Neoplasie insbesondere adenomatöser colorektaler Polypen bei familiärer adenomatöser Polyposis, zur Behandlung von Schmerzen, inbesondere akute Schmerzen, und Dysmenorrhoe, insbesondere primäre Dysmenorrhoe, enthalten.
• Comparison of Iridium(I) Catalysts in Temperature Mediated Hydrogen Isotope Exchange Reactions
  作者：Mégane Valero、Anurag Mishra、Jennifer Blass、Remo Weck、Volker Derdau

  DOI：10.1002/open.201900204

  日期：2019.9

  The reactivity and selectivity of iridium(I) catalysed hydrogen isotope exchange (HIE) reactions can be varied by using wide range of reaction temperatures. Herein, we have done a detailed comparison study with common iridium(I) catalysts (1–6) which will help us to understand and optimize the approaches of either high selectivity or maximum deuterium incorporation. We have demonstrated that the temperature

  铱（I）催化的氢同位素交换（HIE）反应的反应性和选择性可以通过使用宽范围的反应温度来改变。在这里，我们已经做了与普通铱（I）催化剂（详细的比较研究1 - 6），这将有助于我们理解和优化方法无论是高选择性或最大的氘引入的。我们已经证明，这些研究的铱（I）催化剂的温度窗口令人惊讶地非常宽。这一原理在复杂药物分子的某些HIE反应中得到了进一步证明。