3-Diethoxyphosphoryl-3,3-difluoropropan-1-amine | 1408284-07-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: 3-Diethoxyphosphoryl-3,3-difluoropropan-1-amine
• 英文别名: 3-diethoxyphosphoryl-3,3-difluoropropan-1-amine
• CAS: 1408284-07-0
• 化学式: C₇H₁₆F₂NO₃P
• 分子量: 231.18
• InChiKey: NJAFMYBQYWFXEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2N-(N,N-dimethylaminomethylidene)-9-formyl-1N-(pivaloyloxy)methyl-9-deazaguanine 、 3-Diethoxyphosphoryl-3,3-difluoropropan-1-amine 在 溶剂黄146 、 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 39.5h， 以30.3 mg的产率得到9-{[N-[3'',3''-difluoro-3''-(diethylphosphono)propyl]amino]methyl}-2N-(N,N-dimethylaminomethylidene)-1N-(pivaloyloxy)methyl-9-deazaguanine
  参考文献：
  名称：

  Trimeric purine nucleoside phosphorylase: Exploring postulated one-third-of-the-sites binding in the transition state

  摘要：

  Transition-state analogue inhibitors, immucillins, were reported to bind to trimeric purine nucleoside phosphorylase (PNP) with the stoichiometry of one molecule per enzyme trimer [ Miles, R. W.; Tyler, P. C.; Furneaux, R. H.; Bagdassarian, C. K.; Schramm, V. L. Biochem. 1998, 37, 8615]. In attempts to observe and better understand the nature of this phenomenon we have conducted calorimetric titrations of the recombinant calf PNP complexed with immucillin H. However, by striking contrast to the earlier reports, we have not observed negative cooperativity and we got the stoichiometry of three immucillin molecules per enzyme trimer. Similar results were obtained from fluorimetric titrations, and for other inhibitors bearing features of the transition state. However, we observed apparent cooperativity between enzyme subunits and apparent lower stoichiometry when we used the recombinant enzyme not fully purified from hypoxanthine, which is moped from Escherichia coli cells. Results presented here prove that one-third-of-the-sites binding does not occur for trimeric PNP, and give the highly probable explanation why previous experiments were interpreted in terms of this phenomenon. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.08.045
• 作为产物：
  描述：

  diethyl 3-azido-1,1-difluoropropylphosphate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 3-Diethoxyphosphoryl-3,3-difluoropropan-1-amine
  参考文献：
  名称：

  Trimeric purine nucleoside phosphorylase: Exploring postulated one-third-of-the-sites binding in the transition state

  摘要：

  Transition-state analogue inhibitors, immucillins, were reported to bind to trimeric purine nucleoside phosphorylase (PNP) with the stoichiometry of one molecule per enzyme trimer [ Miles, R. W.; Tyler, P. C.; Furneaux, R. H.; Bagdassarian, C. K.; Schramm, V. L. Biochem. 1998, 37, 8615]. In attempts to observe and better understand the nature of this phenomenon we have conducted calorimetric titrations of the recombinant calf PNP complexed with immucillin H. However, by striking contrast to the earlier reports, we have not observed negative cooperativity and we got the stoichiometry of three immucillin molecules per enzyme trimer. Similar results were obtained from fluorimetric titrations, and for other inhibitors bearing features of the transition state. However, we observed apparent cooperativity between enzyme subunits and apparent lower stoichiometry when we used the recombinant enzyme not fully purified from hypoxanthine, which is moped from Escherichia coli cells. Results presented here prove that one-third-of-the-sites binding does not occur for trimeric PNP, and give the highly probable explanation why previous experiments were interpreted in terms of this phenomenon. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.08.045

文献信息

• [EN] NOVEL AROMATIC THIO COMPOUNDS AS RECEPTOR MODULATORS<br/>[FR] NOUVEAUX COMPOSÉS THIO AROMATIQUES UTILISÉS EN TANT QUE MODULATEURS DES RÉCEPTEURS
  申请人：ALLERGAN INC

  公开号：WO2014093253A1

  公开（公告）日：2014-06-19

  The present invention relates to novel aromatic thio derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors.
• Trimeric purine nucleoside phosphorylase: Exploring postulated one-third-of-the-sites binding in the transition state
  作者：Beata Wielgus-Kutrowska、Katarzyna Breer、Mariko Hashimoto、Sadao Hikishima、Tsutomu Yokomatsu、Marta Narczyk、Alicja Dyzma、Agnieszka Girstun、Krzysztof Staroń、Agnieszka Bzowska

  DOI：10.1016/j.bmc.2012.08.045

  日期：2012.11

  Transition-state analogue inhibitors, immucillins, were reported to bind to trimeric purine nucleoside phosphorylase (PNP) with the stoichiometry of one molecule per enzyme trimer [ Miles, R. W.; Tyler, P. C.; Furneaux, R. H.; Bagdassarian, C. K.; Schramm, V. L. Biochem. 1998, 37, 8615]. In attempts to observe and better understand the nature of this phenomenon we have conducted calorimetric titrations of the recombinant calf PNP complexed with immucillin H. However, by striking contrast to the earlier reports, we have not observed negative cooperativity and we got the stoichiometry of three immucillin molecules per enzyme trimer. Similar results were obtained from fluorimetric titrations, and for other inhibitors bearing features of the transition state. However, we observed apparent cooperativity between enzyme subunits and apparent lower stoichiometry when we used the recombinant enzyme not fully purified from hypoxanthine, which is moped from Escherichia coli cells. Results presented here prove that one-third-of-the-sites binding does not occur for trimeric PNP, and give the highly probable explanation why previous experiments were interpreted in terms of this phenomenon. (C) 2012 Elsevier Ltd. All rights reserved.