Tert-butyl 4-[5-chloro-1-(3-chlorophenyl)-6-oxopyridazin-4-yl]piperazine-1-carboxylate | 1062052-14-5

• 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: Tert-butyl 4-[5-chloro-1-(3-chlorophenyl)-6-oxopyridazin-4-yl]piperazine-1-carboxylate
• CAS: 1062052-14-5
• 化学式: C₁₉H₂₂Cl₂N₄O₃
• 分子量: 425.315
• InChiKey: JLMBAFXZXUVANL-UHFFFAOYSA-N

物化性质

• 沸点：
  513.9±60.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  65.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Tert-butyl 4-[5-chloro-1-(3-chlorophenyl)-6-oxopyridazin-4-yl]piperazine-1-carboxylate 在 盐酸 、 sodium hexamethyldisilazane 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 5-(4-Benzylsulfonylpiperazin-1-yl)-2-(3-chlorophenyl)-4-(cyclopentoxy)pyridazin-3-one
  参考文献：
  名称：

  The optimization of pyridazinone series of glucan synthase inhibitors

  摘要：

  A detailed structure-activity relationship study of a novel series of pyridazine-based small molecule glucan synthase inhibitors is described. The optimization of the PK profile of this series led to the discovery of compound 11g, which demonstrated in vivo potency ip in a lethal fungal infection model. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.091
• 作为产物：
  描述：

  3-氯苯肼盐酸盐 在 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 Tert-butyl 4-[5-chloro-1-(3-chlorophenyl)-6-oxopyridazin-4-yl]piperazine-1-carboxylate
  参考文献：
  名称：

  The synthesis and structure–activity relationship of pyridazinones as glucan synthase inhibitors

  摘要：

  A structure-activity relationship study of the lead 5-[4-(benzylsulfonyl) piperazin-1-yl]-4-morpholino-2- phenyl-pyridazin-3(2H)-one 1 has resulted in the identification of 2-(3,5-difluorophenyl)-4-(3-fluorocyclopentyloxy)- 5-[4-(isopropylsulfonyl) piperazin-1-yl]-pyridazin-3(2H)-one 11c as a beta- 1,3-glucan synthase inhibitor. Compound 11c exhibited significant efficacy in an in vivo mouse model of Candida glabrata infection. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.058

文献信息

• Pyridazinone Derivatives Useful as Glucan Synthase Inhibitors
  申请人：Ting Pauline C.

  公开号：US20090170861A1

  公开（公告）日：2009-07-02

  In its many embodiments, the present invention provides -substituted pyridazinone compounds as glucan synthase inhibitors, methods of preparing such compounds, pharmaceutical including one or more of such compounds, methods of preparing pharmaceutical formulations including one or more such compounds or one or more such compounds along with other antifungal agents, and methods of treatment, prevention, inhibition, or amelioration of one or more fungal infections associated with glucan synthase using such compounds or pharmaceutical compositions.

  在其多种实施方式中，本发明提供了取代的吡啶嗪酮化合物作为葡聚糖合成酶抑制剂，制备这种化合物的方法，包括一种或多种这种化合物的制药物，制备包括一种或多种这种化合物或一种或多种这种化合物与其他抗真菌药物共同使用的制药配方的方法，以及使用这种化合物或制药组合物治疗、预防、抑制或改善与葡聚糖合成酶相关的一种或多种真菌感染的方法。
• The synthesis and structure–activity relationship of pyridazinones as glucan synthase inhibitors
  作者：Pauline C. Ting、Rongze Kuang、Heping Wu、Robert G. Aslanian、Jianhua Cao、David W. Kim、Joe F. Lee、John Schwerdt、Gang Zhou、Samuel Wainhaus、Todd A. Black、Anthony Cacciapuoti、Paul M. McNicholas、Yiming Xu、Scott S. Walker

  DOI：10.1016/j.bmcl.2011.01.058

  日期：2011.3

  A structure-activity relationship study of the lead 5-[4-(benzylsulfonyl) piperazin-1-yl]-4-morpholino-2- phenyl-pyridazin-3(2H)-one 1 has resulted in the identification of 2-(3,5-difluorophenyl)-4-(3-fluorocyclopentyloxy)- 5-[4-(isopropylsulfonyl) piperazin-1-yl]-pyridazin-3(2H)-one 11c as a beta- 1,3-glucan synthase inhibitor. Compound 11c exhibited significant efficacy in an in vivo mouse model of Candida glabrata infection. (C) 2011 Elsevier Ltd. All rights reserved.
• PYRIDAZINONE DERIVATIVES USEFUL AS GLUCAN SYNTHASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2137179B1

  公开（公告）日：2015-09-02
• US8232274B2
  申请人：——

  公开号：US8232274B2

  公开（公告）日：2012-07-31
• The optimization of pyridazinone series of glucan synthase inhibitors
  作者：Rongze Kuang、Heping Wu、Pauline C. Ting、Robert G. Aslanian、Jianhua Cao、David W. Kim、Joe F. Lee、John Schwerdt、Gang Zhou、R. Jason Herr、Andrew J. Zych、Jinhai Yang、Sang Q. Lam、David M. Jenkins、Samuel A. Sakwa、Samuel Wainhaus、Todd A. Black、Anthony Cacciapuoti、Paul M. McNicholas、Yiming Xu、Scott S. Walker

  DOI：10.1016/j.bmcl.2012.06.091

  日期：2012.8

  A detailed structure-activity relationship study of a novel series of pyridazine-based small molecule glucan synthase inhibitors is described. The optimization of the PK profile of this series led to the discovery of compound 11g, which demonstrated in vivo potency ip in a lethal fungal infection model. (c) 2012 Elsevier Ltd. All rights reserved.