phenyl N-(6-methoxy-4-methylpyridin-3-yl)carbamate | 1616415-81-6

• 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: phenyl N-(6-methoxy-4-methylpyridin-3-yl)carbamate
• CAS: 1616415-81-6
• 化学式: C₁₄H₁₄N₂O₃
• 分子量: 258.277
• InChiKey: KHNVCLGXXXBTIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  19.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  60.45
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  phenyl N-(6-methoxy-4-methylpyridin-3-yl)carbamate 、 7-(piperazin-1-yl)thiazolo[5,4-d]pyrimidin-5-ylamine hydrochloride 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 生成 4-(5-aminothiazolo[5,4-d]pyrimidin-7-yl)-N-(6-methoxy-4-methyl-3-pyridyl)piperazine-1-carboxamide
  参考文献：
  名称：

  Discovery of a Potent, Orally Bioavailable PI4KIIIβ Inhibitor (UCB9608) Able To Significantly Prolong Allogeneic Organ Engraftment in Vivo

  摘要：

  The primary target of a novel series of immunosuppressive 7-piperazin-1-ylthiazolo[5,4-d]pyrimidin-5-amines was identified as the lipid kinase, PI4KIII beta. Evaluation of the series highlighted their poor solubility and unwanted off-target activities. A medicinal chemistry strategy was put in place to optimize physicochemical properties within the series, while maintaining potency and improving selectivity over other lipid kinases. Compound 22 was initially identified and profiled in vivo, before further modifications led to the discovery of 44 (UCB9608), a vastly more soluble, selective compound with improved metabolic stability and excellent pharmacokinetic profile. A co-crystal structure of 44 with PI4KIII beta was solved, confirming the binding mode of this class of inhibitor. The much-improved in vivo profile of 44 positions it as an ideal tool compound to further establish the link between PI4KIII beta inhibition and prolonged allogeneic organ engraftment, and suppression of immune responses in vivo.

  DOI：

  10.1021/acs.jmedchem.8b00521
• 作为产物：
  描述：

  2-甲氧基-4-甲基-5-氨基吡啶 、 氯甲酸苯酯 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 phenyl N-(6-methoxy-4-methylpyridin-3-yl)carbamate
  参考文献：
  名称：

  Discovery of a Potent, Orally Bioavailable PI4KIIIβ Inhibitor (UCB9608) Able To Significantly Prolong Allogeneic Organ Engraftment in Vivo

  摘要：

  The primary target of a novel series of immunosuppressive 7-piperazin-1-ylthiazolo[5,4-d]pyrimidin-5-amines was identified as the lipid kinase, PI4KIII beta. Evaluation of the series highlighted their poor solubility and unwanted off-target activities. A medicinal chemistry strategy was put in place to optimize physicochemical properties within the series, while maintaining potency and improving selectivity over other lipid kinases. Compound 22 was initially identified and profiled in vivo, before further modifications led to the discovery of 44 (UCB9608), a vastly more soluble, selective compound with improved metabolic stability and excellent pharmacokinetic profile. A co-crystal structure of 44 with PI4KIII beta was solved, confirming the binding mode of this class of inhibitor. The much-improved in vivo profile of 44 positions it as an ideal tool compound to further establish the link between PI4KIII beta inhibition and prolonged allogeneic organ engraftment, and suppression of immune responses in vivo.

  DOI：

  10.1021/acs.jmedchem.8b00521