5-(4,4,5,5-四甲基-1,3,2-二氧硼杂戊环-2-基)呋喃-2-甲腈 | 1111096-21-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 硼酸衍生物
• 中文名称: 5-(4,4,5,5-四甲基-1,3,2-二氧硼杂戊环-2-基)呋喃-2-甲腈
• 英文名称: 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)furan-2-carbonitrile
• CAS: 1111096-21-9
• 化学式: C₁₁H₁₄BNO₃
• 分子量: 219.048
• InChiKey: FJXFCIJNLDIHNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.45
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(4,4,5,5-四甲基-1,3,2-二氧硼杂戊环-2-基)呋喃-2-甲腈 、 5-溴[1,2,4]三唑并[1,5-a]吡啶 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 2.0h， 以25 mg的产率得到5-{[1,2,4]triazolo[1,5-a]pyridin-5-yl}furan-2-carbonitrile
  参考文献：
  名称：

  1,2,4-Triazolo-[1,5-a]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) Inhibitors With a Novel Monodentate Binding Interaction

  摘要：

  Herein we describe the identification of 4-{[1,2,4]triazolo[1,5-a]pyridin-5-yl}benzonitrile-based inhibitors of the hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme. These inhibitors were shown to possess a novel binding mode by X-ray crystallography, in which the triazolo N1 atom coordinates in a hitherto unreported monodentate interaction with the active site Fe2+ ion, while the benzonitrile group accepts a hydrogen -bonding interaction from the side chain residue of Asn315. Further optimization led to potent PHD-1 inhibitors with good physicochemical and pharmacokinetic properties.

  DOI：

  10.1021/acs.jmedchem.7b00352
• 作为产物：
  描述：

  5-溴呋喃-2-甲腈 、 联硼酸频那醇酯 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 生成 5-(4,4,5,5-四甲基-1,3,2-二氧硼杂戊环-2-基)呋喃-2-甲腈
  参考文献：
  名称：

  1,2,4-Triazolo-[1,5-a]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) Inhibitors With a Novel Monodentate Binding Interaction

  摘要：

  Herein we describe the identification of 4-{[1,2,4]triazolo[1,5-a]pyridin-5-yl}benzonitrile-based inhibitors of the hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme. These inhibitors were shown to possess a novel binding mode by X-ray crystallography, in which the triazolo N1 atom coordinates in a hitherto unreported monodentate interaction with the active site Fe2+ ion, while the benzonitrile group accepts a hydrogen -bonding interaction from the side chain residue of Asn315. Further optimization led to potent PHD-1 inhibitors with good physicochemical and pharmacokinetic properties.

  DOI：

  10.1021/acs.jmedchem.7b00352

文献信息

• [EN] NEW THIENOPYRIMIDINE DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM<br/>[FR] NOUVEAUX DÉRIVÉS DE THIÉNOPYRIMIDINE, PROCÉDÉ POUR LEUR PRÉPARATION ET COMPOSITIONS PHARMACEUTIQUES LES CONTENANT
  申请人：SERVIER LAB

  公开号：WO2015097123A1

  公开（公告）日：2015-07-02

  Compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, R12, X, A and n are as defined in the description.

  式（I）的化合物：其中R1、R2、R3、R4、R5、R6、R7、R12、X、A和n的定义如描述中所述。
• 1,2,4-Triazolo-[1,5-<i>a</i>]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) Inhibitors With a Novel Monodentate Binding Interaction
  作者：Saleh Ahmed、Andrew Ayscough、Greg R. Barker、Hannah E. Canning、Richard Davenport、Robert Downham、David Harrison、Kerry Jenkins、Natasha Kinsella、David G. Livermore、Susanne Wright、Anthony D. Ivetac、Robert Skene、Steven J. Wilkens、Natalie A. Webster、Alan G. Hendrick

  DOI：10.1021/acs.jmedchem.7b00352

  日期：2017.7.13

  Herein we describe the identification of 4-[1,2,4]triazolo[1,5-a]pyridin-5-yl}benzonitrile-based inhibitors of the hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme. These inhibitors were shown to possess a novel binding mode by X-ray crystallography, in which the triazolo N1 atom coordinates in a hitherto unreported monodentate interaction with the active site Fe2+ ion, while the benzonitrile group accepts a hydrogen -bonding interaction from the side chain residue of Asn315. Further optimization led to potent PHD-1 inhibitors with good physicochemical and pharmacokinetic properties.