di-isopropylphosphonate anion

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: di-isopropylphosphonate anion
• 英文别名: Diisopropyl phosphate；dipropan-2-yl phosphate
• 化学式: C₆H₁₄O₄P
• 分子量: 181.149
• InChiKey: WZPMZMCZAGFKOC-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙酸铵 、 苯甲醛 、 di-isopropylphosphonate anion 在 ice water 、 乙醚 、 二氯甲烷 、 Brine 、 Sodium sulfate-III 、 diisopropyl [amino(phenyl)methyl]phosphonate 作用下， 以 乙醇 为溶剂， 反应 48.0h， 以to give the title compound, 6-b, (253.0 g, 41%)的产率得到diisopropyl [amino(phenyl)methyl]phosphonate
  参考文献：
  名称：

  Substituted pyrimidines

  摘要：

  本发明涉及替代嘧啶类化合物，可作为HIF脯氨酸羟化酶抑制剂用于治疗贫血和类似疾病。

  公开号：

  US09079930B2
• 作为产物：
  描述：

  3-氟-4-甲氧基苯乙酮 、 水 生成 di-isopropylphosphonate anion 、 氟离子（F-） 、 氢(+1)阳离子
  参考文献：
  名称：

  通过动力学研究，化学修饰和定点诱变，了解了来自Loligo vulgaris的二异丙基氟磷酸酶的反应机理。

  摘要：

  动力学测量，化学修饰和定点诱变已被用来深入了解寻常Loligo的二异丙基氟磷酸酶（DFPase）的反应机理。氟磷酸二异丙酯水解动力学的分析表明，在pH> / = 8、35摄氏度和500 mM NaCl的离子强度下，最佳的酶活性，其中k（cat）达到极限值526 s（-1）。pH速率曲线表明，在25摄氏度下，完全的催化活性需要使表观pK（a）为6.82，DeltaH（ion）为42 kJ / mol和DeltaS（ion）为9.8 J / mol K的可电离基团去质子化。天冬氨酸，谷氨酸，半胱氨酸，精氨酸，赖氨酸和酪氨酸残基的化学修饰表明这些氨基酸对于催化不是关键。DFPase中存在的六个组氨酸残基中没有一个与焦碳酸二乙酯（DEPC）发生反应，这表明DEPC无法接近组氨酸。因此，所有六个组氨酸残基已分别被天冬酰胺取代，以鉴定参与催化的残基。仅H287的取代使该酶催化上几乎无活性，残余活性为约

  DOI：

  10.1016/s0167-4838(01)00153-4

文献信息

• SUBSTITUTED PYRIMIDINES
  申请人：MERCK SHARP & DOHME CORP

  公开号：US20140349972A1

  公开（公告）日：2014-11-27

  The present invention relates to substituted pyrimidines useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.

  本发明涉及替代嘧啶类化合物，用于治疗贫血和类似疾病的HIF脯氨酸羟化酶抑制剂。
• Insights into the reaction mechanism of the diisopropyl fluorophosphatase from Loligo vulgaris by means of kinetic studies, chemical modification and site-directed mutagenesis
  作者：Judith Hartleib、Heinz Rüterjans

  DOI：10.1016/s0167-4838(01)00153-4

  日期：2001.4

  deprotonation of an ionizable group with an apparent pK(a) of 6.82, DeltaH(ion) of 42 kJ/mol and DeltaS(ion) of 9.8 J/mol K at 25 degrees C. Chemical modification of aspartate, glutamate, cysteine, arginine, lysine and tyrosine residues indicates that these amino acids are not critical for catalysis. None of the six histidine residues present in DFPase reacts with diethyl pyrocarbonate (DEPC), suggesting

  动力学测量，化学修饰和定点诱变已被用来深入了解寻常Loligo的二异丙基氟磷酸酶（DFPase）的反应机理。氟磷酸二异丙酯水解动力学的分析表明，在pH> / = 8、35摄氏度和500 mM NaCl的离子强度下，最佳的酶活性，其中k（cat）达到极限值526 s（-1）。pH速率曲线表明，在25摄氏度下，完全的催化活性需要使表观pK（a）为6.82，DeltaH（ion）为42 kJ / mol和DeltaS（ion）为9.8 J / mol K的可电离基团去质子化。天冬氨酸，谷氨酸，半胱氨酸，精氨酸，赖氨酸和酪氨酸残基的化学修饰表明这些氨基酸对于催化不是关键。DFPase中存在的六个组氨酸残基中没有一个与焦碳酸二乙酯（DEPC）发生反应，这表明DEPC无法接近组氨酸。因此，所有六个组氨酸残基已分别被天冬酰胺取代，以鉴定参与催化的残基。仅H287的取代使该酶催化上几乎无活性，残余活性为约
• Column Chromatography-Free Solution-Phase Synthesis of a Natural Piper-Amide-like Compound Library
  作者：Sumin Kim、Chaemin Lim、Sukjin Lee、Seokwoo Lee、Hyunkyung Cho、Joo-Youn Lee、Dong Sup Shim、Hee Dong Park、Sanghee Kim

  DOI：10.1021/co400003d

  日期：2013.4.8

  We have achieved an efficient solution-phase parallel synthesis of a library of natural piper-amide-like compounds from the bifunctional beta-phosphono-N-hydroxy-succinimidyl ester intermediate. The primary important feature in our study is the construction of natural-product-like molecules through the adaptation of sophisticated organic reactions that create water-soluble byproducts for a chromatography-free purification. This simple and efficient method rapidly provides a combinatorial library of high yield and purity. The library was evaluated against GPCR targets to demonstrate its potential use as a tool for drug discovery and in chemical biology.
• Substituted pyrimidines
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US09079930B2

  公开（公告）日：2015-07-14

  The present invention relates to substituted pyrimidines useful as HIF prolyl hydroxylase inhibitors to treat anemia and like conditions.

  本发明涉及替代嘧啶类化合物，可作为HIF脯氨酸羟化酶抑制剂用于治疗贫血和类似疾病。
• Role of calcium ions in the structure and function of thedi-isopropylfluorophosphatase from Loligo vulgaris
  作者：Judith HARTLEIB、Stefan GESCHWINDNER、Eileen I. SCHARFF、Heinz RÜTERJANS

  DOI：10.1042/0264-6021:3530579

  日期：2001.2.1

  Di-isopropylfluorophosphatase (DFPase) is shown to contain two high-affinity Ca2+-binding sites, which are required for catalytic activity and stability. Incubation with chelating agents results in the irreversible inactivation of DFPase. From titrations with Quin 2[2-(2-[bis(carboxymethyl)amino]-5-methylphenoxy}-methyl)-6-methoxy-8-[bis(carboxymethyl)-amino]quinoline], a lower-affinity site with dissociation constants of 21 and 840 nM in the absence and the presence of 150 mM KCI respectively was calculated. The higher-affinity site was not accessible, indicating a dissociation constant of less than 5.3 nM. Stopped-flow experiments have shown that the dissociation of bound Ca2+ occurs in two phases, with rates of approx. 1.1 and 0.026 s(-1) corresponding to the dissociation from the low-affinity and high-affinity sites respectively. Dissociation rates depend strongly on temperature but not on ionic strength, indicating that Ca2+ dissociation is connected with conformational changes. Limited proteolysis, CD spectroscopy, dynamic light scattering and the binding of 8-anilino-1-naphthalenesulphonic acid have been combined to give a detailed picture of the conformational changes induced on the removal of Ca2+ from DFPase. The Ca2+ dissociation is shown to result in a primary, at least partly reversible, step characterized by a large decrease in DFPase activity and some changes in enzyme structure and shape. This step is followed by an irreversible denaturation and aggregation of the ape-enzyme. From the temperature dependence of Ca2+ dissociation and the denaturation results we conclude that the higher-affinity Ca2+ site is required for stabilizing DFPase's structure, whereas the lower-affinity site is likely to fulfil a catalytic function.