tert-butyl 2-(2,4-dichlorobenzylidene)-3-oxobutanoate | 896459-74-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: tert-butyl 2-(2,4-dichlorobenzylidene)-3-oxobutanoate
• 英文别名: tert-butyl 2-[(2,4-dichlorophenyl)methylidene]-3-oxobutanoate
• CAS: 896459-74-8
• 化学式: C₁₅H₁₆Cl₂O₃
• 分子量: 315.196
• InChiKey: KDEXJMVQINWSRK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-(2,4-dichlorobenzylidene)-3-oxobutanoate 、 3-氨基吡唑 在 sodium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成
  参考文献：
  名称：

  Dihydropyrazolopyrimidine Inhibitors of KV1.5 (IKur)

  摘要：

  A series of dihydropyrazolopyrimidine inhibitors of K(V)1.5 (I-Kur) have been identified. The synthesis, structure-activity relationships and selectivity against several other ion channels are described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.099
• 作为产物：
  描述：

  乙酰乙酸叔丁酯 、 2,4-二氯苯甲醛 在 哌啶 、 溶剂黄146 作用下， 以 甲苯 为溶剂， 生成 tert-butyl 2-(2,4-dichlorobenzylidene)-3-oxobutanoate
  参考文献：
  名称：

  Dihydropyrazolopyrimidine Inhibitors of KV1.5 (IKur)

  摘要：

  A series of dihydropyrazolopyrimidine inhibitors of K(V)1.5 (I-Kur) have been identified. The synthesis, structure-activity relationships and selectivity against several other ion channels are described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.099

文献信息

• Azolopyrimidine-based inhibitors of dipeptidyl peptidase IV and methods
  申请人：Meng Wei

  公开号：US20060178377A1

  公开（公告）日：2006-08-10

  Compounds are provided having the formula (I) wherein R, X, Y, A and n are as defined herein.

  提供化合物的公式(I)，其中R、X、Y、A和n的定义如下。
• Discovery of 6-(Aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-<i>a</i>]pyrimidine-2-carboxamides as Potent, Selective Dipeptidyl Peptidase-4 (DPP4) Inhibitors
  作者：Wei Meng、Robert P. Brigance、Hannguang J. Chao、Aberra Fura、Thomas Harrity、Jovita Marcinkeviciene、Stephen P. O’Connor、James K. Tamura、Dianlin Xie、Yaqun Zhang、Herbert E. Klei、Kevin Kish、Carolyn A. Weigelt、Huji Turdi、Aiying Wang、Robert Zahler、Mark S. Kirby、Lawrence G. Hamann

  DOI：10.1021/jm100634a

  日期：2010.8.12

  Continued structure activity relationship (SA R) exploration within our previously disclosed azolopyrimidine containing dipeptidyl peptidase-4 (DPP4) inhibitors led us to focus on an imidazolopyrimidine series in particular. Further study revealed that by replacing the aryl substitution on the imidazole ring with a more polar carboxylic ester or amide, these compounds displayed not only increased DPP4 binding activity but also significantly reduced human ether-a-go-go related gene (hERG) and sodium channel inhibitory activities. Additional incremental adjustment of polarity led to permeable molecules which exhibited favorable pharmacokinetic (PK) profiles in preclinical animal species. The active site binding mode of these compounds was determined by X-ray crystallography as exemplified by amide 24c. A subsequent lead molecule from this series, (+)-6-(aminomethyl)-5-(2,4-dichlorophenyl)-N-(1-ethyl-1H-pyrazol-5-yl)-7-methylimidazo[1,2-c]pyrimidine-2-carboxamide (24s), emerged as a potent, selective DPP4 inhibitor that displayed excellent PK profiles and in vivo efficacy in ob/ob mice.
• WO2006/71752
  申请人：——

  公开号：——

  公开（公告）日：——
• Dihydropyrazolopyrimidine Inhibitors of KV1.5 (IKur)
  作者：Wayne Vaccaro、Tram Huynh、John Lloyd、Karnail Atwal、Heather J. Finlay、Paul Levesque、Mary Lee Conder、Tonya Jenkins-West、Hong Shi、Lucy Sun

  DOI：10.1016/j.bmcl.2008.10.099

  日期：2008.12

  A series of dihydropyrazolopyrimidine inhibitors of K(V)1.5 (I-Kur) have been identified. The synthesis, structure-activity relationships and selectivity against several other ion channels are described. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and SAR of azolopyrimidines as potent and selective dipeptidyl peptidase-4 (DPP4) inhibitors for type 2 diabetes
  作者：Robert P. Brigance、Wei Meng、Aberra Fura、Thomas Harrity、Aiying Wang、Robert Zahler、Mark S. Kirby、Lawrence G. Hamann

  DOI：10.1016/j.bmcl.2010.06.063

  日期：2010.8

  Several pyrazolo-, triazolo-, and imidazolopyrimidines were synthesized and evaluated as inhibitors of DPP4. Of these three classes of compounds, the imidazolopyrimidines displayed the greatest potency and demonstrated excellent selectivity over the other dipeptidyl peptidases. SAR evaluation for these scaffolds was described as they may represent potential treatments for type 2 diabetes. (C) 2010 Elsevier Ltd. All rights reserved.