tert-butyl (4-chloro-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate | 1240286-90-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl (4-chloro-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate
• 英文别名: Tert-butyl{4-chloro-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate；tert-butyl 2-[4-chloro-2-[2-(3-propylsulfonylphenyl)ethynyl]phenoxy]acetate
• CAS: 1240286-90-1
• 化学式: C₂₃H₂₅ClO₅S
• 分子量: 448.967
• InChiKey: IWRCDTAPNHDPHZ-UHFFFAOYSA-N

物化性质

• 沸点：
  612.5±55.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-chloro-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate 在 盐酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 {4-chloro-2-[(3-propylsulfonylphenyl)ethynyl]phenoxy}acetic acid
  参考文献：
  名称：

  Discovery of Potent, Selective, and Orally Bioavailable Alkynylphenoxyacetic Acid CRTH2 (DP2) Receptor Antagonists for the Treatment of Allergic Inflammatory Diseases

  摘要：

  New phenoxyacetic acid antagonists of CRTH2 are described. Following the discovery of a hit compound by a focused screening, high protein binding was identified as its main weakness. Optimization aimed at reducing serum protein binding led to the identification of several compounds that showed not only excellent affinities for the receptor (41 compounds with K-i < 10 nM) but also excellent potencies in a human whole blood assay (IC50 < 100 nM; PGD2-induced eosinophil shape change). Additional optimization of the PK characteristics led to the identification of several compounds suitable for in vivo testing. Of these, 19k and 19s were tested in two different pharmacological models (acute FITC-mediated contact hypersensitivity and ovalbumin-induced eosinophilia models) and found to be active after oral dosing (10 and 30 mg/kg).

  DOI：

  10.1021/jm200866y
• 作为产物：
  描述：

  2-溴-4-氯苯酚 在 哌啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 trans-bis(triphenylphosphine)palladium dichloride 、 四丁基氟化铵 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 64.34h， 生成 tert-butyl (4-chloro-2-{[3-(propylsulfonyl)phenyl]ethynyl}phenoxy)acetate
  参考文献：
  名称：

  Discovery of Potent, Selective, and Orally Bioavailable Alkynylphenoxyacetic Acid CRTH2 (DP2) Receptor Antagonists for the Treatment of Allergic Inflammatory Diseases

  摘要：

  New phenoxyacetic acid antagonists of CRTH2 are described. Following the discovery of a hit compound by a focused screening, high protein binding was identified as its main weakness. Optimization aimed at reducing serum protein binding led to the identification of several compounds that showed not only excellent affinities for the receptor (41 compounds with K-i < 10 nM) but also excellent potencies in a human whole blood assay (IC50 < 100 nM; PGD2-induced eosinophil shape change). Additional optimization of the PK characteristics led to the identification of several compounds suitable for in vivo testing. Of these, 19k and 19s were tested in two different pharmacological models (acute FITC-mediated contact hypersensitivity and ovalbumin-induced eosinophilia models) and found to be active after oral dosing (10 and 30 mg/kg).

  DOI：

  10.1021/jm200866y

文献信息

• [EN] PHENOXY ACETIC ACID DERIVATIVES<br/>[FR] DÉRIVÉS D'ACIDE PHÉNOXYACÉTIQUE
  申请人：MERCK SERONO SA

  公开号：WO2010092043A1

  公开（公告）日：2010-08-19

  The present invention provides phenoxyacetic acid derivatives of Formula (I) for the treatment of CRTH2 related disorders and disease selected from asthma, atopic dermatitis and inflammatory dermatoses.

  本发明提供了用于治疗与CRTH2相关的疾病和疾病（包括哮喘、特应性皮炎和炎症性皮肤病）的Formula（I）的苯氧乙酸衍生物。
• PHENOXY ACETIC ACID DERIVATIVES
  申请人：Crosignani Stefano

  公开号：US20110288066A1

  公开（公告）日：2011-11-24

  The present invention provides phenoxyacetic acid derivatives of Formula (I) for the treatment of CRTH2 related disorders and disease selected from asthma, atopic dermatitis and inflammatory dermatoses.

  本发明提供了公式(I)的苯氧乙酸衍生物，用于治疗与CRTH2相关的疾病和疾病，包括哮喘，特应性皮炎和炎症性皮肤病。
• Phenoxy acetic acid derivatives
  申请人：Merck Serono SA

  公开号：US08273769B2

  公开（公告）日：2012-09-25

  The present invention provides phenoxyacetic acid derivatives of Formula (I) for the treatment of CRTH2 related disorders and disease selected from asthma, atopic dermatitis and inflammatory dermatoses.

  本发明提供了式（I）的苯氧乙酸衍生物，用于治疗与CRTH2相关的疾病和疾病，包括哮喘、特应性皮炎和炎症性皮肤病。
• US8273769B2
  申请人：——

  公开号：US8273769B2

  公开（公告）日：2012-09-25