[4-chloro-2-[[(3S)-3-methyl-1-piperazinyl]methyl]phenoxy]acetic acid 1,1-dimethylethyl ester trifluoroacetate | 888973-04-4

• 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: [4-chloro-2-[[(3S)-3-methyl-1-piperazinyl]methyl]phenoxy]acetic acid 1,1-dimethylethyl ester trifluoroacetate
• 英文别名: tert-butyl 2-[4-chloro-2-[[(3S)-3-methylpiperazin-1-yl]methyl]phenoxy]acetate;2,2,2-trifluoroacetic acid
• CAS: 888973-04-4
• 化学式: C₂HF₃O₂*C₁₈H₂₇ClN₂O₃
• 分子量: 468.901
• InChiKey: SGGIXIMBHPDKBR-ZOWNYOTGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.49
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  [4-chloro-2-[[(3S)-3-methyl-1-piperazinyl]methyl]phenoxy]acetic acid 1,1-dimethylethyl ester trifluoroacetate 在 碳酸氢钠 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 32.0h， 生成 2-[4-chloro-2-[[ (3S)-4-[2-(4-chlorophenyl)acetyl]-3-methyl-1-piperazinyl]methyl]phenoxy]acetic acid
  参考文献：
  名称：

  Zwitterionic CRTh2 Antagonists

  摘要：

  A novel series of zwitterions is reported that contains potent, selective antagonists of the chemoattractant receptor-homologous expressed on Th2 lymphocytes receptor (CRTh2 or DP2). A high quality lead compound 2 was discovered from virtual screening based on the pharmacophore features present in a literature compound 1. Lead optimization through side chain modification and preliminary changes around the acid are disclosed. Optimization of physicochemical properties (log D, MWt, and HBA) allowed maintenance of high CRTh2 potency while achieving low rates of metabolism and minimization of other potential concerns such as hERG channel activity and permeability. A step-change increase in potency was achieved through addition of a single methyl group onto the piperazine ring, which gave high quality compounds suitable for progression into in vivo studies.

  DOI：

  10.1021/jm1014549
• 作为产物：
  描述：

  (S)-1-N-Boc-2-甲基哌嗪 在 magnesium sulfate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 40.0h， 生成 [4-chloro-2-[[(3S)-3-methyl-1-piperazinyl]methyl]phenoxy]acetic acid 1,1-dimethylethyl ester trifluoroacetate
  参考文献：
  名称：

  Zwitterionic CRTh2 Antagonists

  摘要：

  A novel series of zwitterions is reported that contains potent, selective antagonists of the chemoattractant receptor-homologous expressed on Th2 lymphocytes receptor (CRTh2 or DP2). A high quality lead compound 2 was discovered from virtual screening based on the pharmacophore features present in a literature compound 1. Lead optimization through side chain modification and preliminary changes around the acid are disclosed. Optimization of physicochemical properties (log D, MWt, and HBA) allowed maintenance of high CRTh2 potency while achieving low rates of metabolism and minimization of other potential concerns such as hERG channel activity and permeability. A step-change increase in potency was achieved through addition of a single methyl group onto the piperazine ring, which gave high quality compounds suitable for progression into in vivo studies.

  DOI：

  10.1021/jm1014549