trans-5'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2',3'-dihydrospiro[cyclohexane-1,1'-indene]-4-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: trans-5'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2',3'-dihydrospiro[cyclohexane-1,1'-indene]-4-carboxylic acid
• 英文别名: 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)spiro[1,2-dihydroindene-3,4'-cyclohexane]-1'-carboxylic acid
• 化学式: C₂₁H₂₉BO₄
• 分子量: 356.27
• InChiKey: MJJXJHCLOYUPNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.44
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans-5'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2',3'-dihydrospiro[cyclohexane-1,1'-indene]-4-carboxylic acid 在 叠氮基三甲基硅烷 、 偶氮二甲酸二异丙酯 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 89.03h， 生成 3-{5-[trans-5'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2',3'-dihydrospiro[cyclohexane-1,1'-inden]-4-yl]-1H-tetrazol-1-yl}propanenitrile
  参考文献：
  名称：

  Design and Optimization of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase 1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide Phenylcyclohexylacetic Acid (AZD7687)

  摘要：

  A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.

  DOI：

  10.1021/jm301296t
• 作为产物：
  描述：

  5-bromo-1-(methoxymethylene)-2,3-dihydro-1H-indene 在 4-二甲氨基吡啶 、 1,1'-双(二苯基膦)二茂铁 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 Oxone 、 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 potassium acetate 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 、 叔丁醇 为溶剂， 反应 116.17h， 生成 trans-5'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2',3'-dihydrospiro[cyclohexane-1,1'-indene]-4-carboxylic acid
  参考文献：
  名称：

  Design and Optimization of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase 1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide Phenylcyclohexylacetic Acid (AZD7687)

  摘要：

  A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.

  DOI：

  10.1021/jm301296t

文献信息

• Design and Optimization of Pyrazinecarboxamide-Based Inhibitors of Diacylglycerol Acyltransferase 1 (DGAT1) Leading to a Clinical Candidate Dimethylpyrazinecarboxamide Phenylcyclohexylacetic Acid (AZD7687)
  作者：Jonas G. Barlind、Udo A. Bauer、Alan M. Birch、Susan Birtles、Linda K. Buckett、Roger J. Butlin、Robert D. M. Davies、Jan W. Eriksson、Clare D. Hammond、Ragnar Hovland、Petra Johannesson、Magnus J. Johansson、Paul D. Kemmitt、Bo T. Lindmark、Pablo Morentin Gutierrez、Tobias A. Noeske、Andreas Nordin、Charles J. O’Donnell、Annika U. Petersson、Alma Redzic、Andrew V. Turnbull、Johanna Vinblad

  DOI：10.1021/jm301296t

  日期：2012.12.13

  A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.