(S)-tert-butyl 4-(4-chlorophthalazin-1-yl)-3-methylpiperazine-1-carboxylate | 1228022-29-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (S)-tert-butyl 4-(4-chlorophthalazin-1-yl)-3-methylpiperazine-1-carboxylate
• 英文别名: tert-butyl (3S)-4-(4-chlorophthalazin-1-yl)-3-methylpiperazine-1-carboxylate
• CAS: 1228022-29-4
• 化学式: C₁₈H₂₃ClN₄O₂
• 分子量: 362.859
• InChiKey: FCBOLKCHKKSBFG-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 4-(4-chlorophthalazin-1-yl)-3-methylpiperazine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以100%的产率得到(R)-1-chloro-4-(2-methylpiperazin-1-yl)phthalazine
  参考文献：
  名称：

  Design of 1-piperazinyl-4-arylphthalazines as potent Smoothened antagonists

  摘要：

  The Hedgehog (Hh) signaling pathway regulates cell proliferation and differentiation in developing tissues, and abnormal activation of the Hh pathway has been linked to several tumor subsets. As a transducer of Hh signaling, the GPCR-like protein Smoothened (Smo) is a promising target for disruption of unregulated Hh signaling. A series of 1-amino-4-arylphthalazines was developed as potent and orally bioavailable inhibitors of Smo. A representative compound from this class demonstrated significant tumor volume reduction in a mouse medulloblastoma model. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.110
• 作为产物：
  描述：

  1,4-二氯酞嗪 、 (S)-4-N-叔丁氧羰基-2-甲基哌嗪 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 48.0h， 以33%的产率得到(S)-tert-butyl 4-(4-chlorophthalazin-1-yl)-3-methylpiperazine-1-carboxylate
  参考文献：
  名称：

  DISUBSTITUTED PHTHALAZINE HEDGEHOG PATHWAY ANTAGONISTS

  摘要：

  本发明提供了一种新型的1,4-二取代邻苯二酮刺猬途径拮抗剂，可用于治疗癌症。

  公开号：

  US20110190304A1

文献信息

• DISUBSTITUTED PHTHALAZINE HEDGEHOG PATHWAY ANTAGONISTS
  申请人：Bastian Jolie Anne

  公开号：US20110190304A1

  公开（公告）日：2011-08-04

  The present invention provides novel 1,4-disubstituted phthalazine hedgehog pathway antagonists useful in the treatment of cancer.

  本发明提供了一种新型的1,4-二取代邻苯二酮刺猬途径拮抗剂，可用于治疗癌症。
• Disubstituted phthalazine hedgehog pathway antagonists
  申请人：Bastian Jolie Anne

  公开号：US08404687B2

  公开（公告）日：2013-03-26

  The present invention provides novel 1,4-disubstituted phthalazine hedgehog pathway antagonists useful in the treatment of cancer.

  本发明提供了一种新型的1,4-二取代菲嗪刺猬途径拮抗剂，可用于治疗癌症。
• US8404687B2
  申请人：——

  公开号：US8404687B2

  公开（公告）日：2013-03-26
• [EN] DISUBSTITUTED PHTHALAZINE HEDGEHOG PATHWAY ANTAGONISTS<br/>[FR] ANTAGONISTES PHTALAZINE DISUBSTITUÉE DE LA VOIE DE SIGNALISATION HEDGEHOG
  申请人：LILLY CO ELI

  公开号：WO2010062507A1

  公开（公告）日：2010-06-03

  The present invention provides novel 1,4-disubstituted phthalazine hedgehog pathway antagonists useful in the treatment of cancer.
• Design of 1-piperazinyl-4-arylphthalazines as potent Smoothened antagonists
  作者：Brian S. Lucas、Wade Aaron、Songzhu An、Richard J. Austin、Matthew Brown、Hon Chan、Angela Chong、Randall Hungate、Tom Huang、Ben Jiang、Michael G. Johnson、Jacob A. Kaizerman、Gary Lee、Dustin L. McMinn、Jessica Orf、Jay P. Powers、Minqing Rong、Maria M. Toteva、Craig Uyeda、Dineli Wickramasinghe、Guifen Xu、Qiuping Ye、Wendy Zhong

  DOI：10.1016/j.bmcl.2010.04.110

  日期：2010.6

  The Hedgehog (Hh) signaling pathway regulates cell proliferation and differentiation in developing tissues, and abnormal activation of the Hh pathway has been linked to several tumor subsets. As a transducer of Hh signaling, the GPCR-like protein Smoothened (Smo) is a promising target for disruption of unregulated Hh signaling. A series of 1-amino-4-arylphthalazines was developed as potent and orally bioavailable inhibitors of Smo. A representative compound from this class demonstrated significant tumor volume reduction in a mouse medulloblastoma model. (C) 2010 Elsevier Ltd. All rights reserved.