(4-amino-3-chlorophenyl)(S,S-dioxothiomorpholino)methanone | 1400287-09-3

• 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-amino-3-chlorophenyl)(S,S-dioxothiomorpholino)methanone
• 英文别名: (4-amino-3-chlorophenyl)(S,S-dioxo-thiomorpholino)methanone；(4-Amino-3-chlorophenyl)-(1,1-dioxo-1,4-thiazinan-4-yl)methanone
• CAS: 1400287-09-3
• 化学式: C₁₁H₁₃ClN₂O₃S
• mdl: MFCD20159211
• 分子量: 288.755
• InChiKey: USJBBWBDVIPXEQ-UHFFFAOYSA-N

物化性质

• 沸点：
  596.3±50.0 °C(predicted)
• 密度：
  1.478±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  88.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (4-amino-3-chlorophenyl)(S,S-dioxothiomorpholino)methanone 、 tert-butyl-6-bromo-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxyla 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 N,N-二甲基乙酰胺 为溶剂， 反应 3.0h， 以62%的产率得到tert-butyl 6-(2-chloro-4-(S,S-dioxo-thiomorpholine-4-carbonyl)phenylamino)-2-(1-methyl-1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridine-1-carboxylate
  参考文献：
  名称：

  Structure-Based Design of Orally Bioavailable 1H-Pyrrolo[3,2-c]pyridine Inhibitors of Mitotic Kinase Monopolar Spindle 1 (MPS1)

  摘要：

  The protein kinase MPS1 is a crucial component of the spindle assembly checkpoint signal and is aberrantly over-expressed in many human cancers. MPS1 is one of the top 25 genes overexpressed in tumors with chromosomal instability and aneuploidy. PTEN-deficient breast tumor cells are particularly dependent upon MPS1 for their survival, making it a target of significant interest in oncology. We report the discovery and optimization of potent and selective MPS1 inhibitors based on the 1H-pyrrolo[3,2-c]pyridine scaffold, guided by structure-based design and cellular characterization of MPS1 inhibition, leading to 65 (CCT251455). This potent and selective chemical tool stabilizes an inactive conformation of MPS1 with the activation loop ordered in a manner incompatible with ATP and substrate-peptide binding; it displays a favorable oral pharmacokinetic profile, shows dose-dependent inhibition of MPS1 in an HCT116 human tumor xenograft model, and is an attractive tool compound to elucidate further the therapeutic potential of MPS1 inhibition.

  DOI：

  10.1021/jm401395s
• 作为产物：
  描述：

  硫代吗啉-1,1-二氧化物 、 3-氯-4-氨基苯甲酸 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以63%的产率得到(4-amino-3-chlorophenyl)(S,S-dioxothiomorpholino)methanone
  参考文献：
  名称：

  Structure-Based Design of Orally Bioavailable 1H-Pyrrolo[3,2-c]pyridine Inhibitors of Mitotic Kinase Monopolar Spindle 1 (MPS1)

  摘要：

  The protein kinase MPS1 is a crucial component of the spindle assembly checkpoint signal and is aberrantly over-expressed in many human cancers. MPS1 is one of the top 25 genes overexpressed in tumors with chromosomal instability and aneuploidy. PTEN-deficient breast tumor cells are particularly dependent upon MPS1 for their survival, making it a target of significant interest in oncology. We report the discovery and optimization of potent and selective MPS1 inhibitors based on the 1H-pyrrolo[3,2-c]pyridine scaffold, guided by structure-based design and cellular characterization of MPS1 inhibition, leading to 65 (CCT251455). This potent and selective chemical tool stabilizes an inactive conformation of MPS1 with the activation loop ordered in a manner incompatible with ATP and substrate-peptide binding; it displays a favorable oral pharmacokinetic profile, shows dose-dependent inhibition of MPS1 in an HCT116 human tumor xenograft model, and is an attractive tool compound to elucidate further the therapeutic potential of MPS1 inhibition.

  DOI：

  10.1021/jm401395s

文献信息

• PYRROLOPYRIDINEAMINO DERIVATIVES AS MPS1 INHIBITORS
  申请人：Cancer Research Technology Ltd

  公开号：EP2686318B1

  公开（公告）日：2016-03-09
• US9371319B2
  申请人：——

  公开号：US9371319B2

  公开（公告）日：2016-06-21