N-叔-丁基氧羰基氨基KU-0058948 | 874116-49-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: N-叔-丁基氧羰基氨基KU-0058948
• 英文名称: tert-butyl 4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)-1,4-diazepane-1-carboxylate
• 英文别名: tert-butyl 4-[3-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-1,4-diazepane-1-carboxylate；N-tert-Butyloxycarbonylamino KU-0058948；tert-butyl 4-[2-fluoro-5-[(4-oxo-3H-phthalazin-1-yl)methyl]benzoyl]-1,4-diazepane-1-carboxylate
• CAS: 874116-49-1
• 化学式: C₂₆H₂₉FN₄O₄
• 分子量: 480.539
• InChiKey: GIMHNPLCMDJBSP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-叔-丁基氧羰基氨基KU-0058948 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 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 、 N,N-二甲基甲酰胺 为溶剂， 反应 74.0h， 生成 1-(4-(2-fluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoyl)-1,4-diazepan-1-yl)-2-(furan-2-yl)ethane-1,2-dione
  参考文献：
  名称：

  HETEROCYCLIC DERIVATES, PREPARATION PROCESSES AND MEDICAL USES THEREOF

  摘要：

  揭示了杂环衍生物，制备方法，含有它们的组合物以及它们的用途。特别地，揭示了它们作为PARP抑制剂的药用。

  公开号：

  US20130224107A1
• 作为产物：
  描述：

  3-溴-4-氟苯甲醛 在 盐酸 、 水 、 一水合肼 、 三乙胺 、 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 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 N-叔-丁基氧羰基氨基KU-0058948
  参考文献：
  名称：

  HETEROCYCLIC DERIVATES, PREPARATION PROCESSES AND MEDICAL USES THEREOF

  摘要：

  揭示了杂环衍生物，制备方法，含有它们的组合物以及它们的用途。特别地，揭示了它们作为PARP抑制剂的药用。

  公开号：

  US20130224107A1

文献信息

• [EN] HETEROCYCLIC DERIVATES,PREPARATION PROCESSES AND MEDICAL USES THEREOF<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES, LEURS PROCÉDÉS DE PRÉPARATION ET LEURS UTILISATIONS MÉDICALES
  申请人：SHANGHAI DE NOVO PHARMATECH CO LTD

  公开号：WO2012071684A1

  公开（公告）日：2012-06-07

  Disclosed are heterocyclic derivatives, methods for making them, compositions containing the same and uses thereof. Particularly, their pharmaceutical use as inhibitors of PARP is disclosed.

  揭示了杂环衍生物，制备它们的方法，含有它们的组合物以及它们的用途。特别地，揭示了它们作为PARP抑制剂的药用。
• Substituted phthalazin-1(2H)-ones, preparation processes and medical uses thereof
  申请人：Gao Daxin

  公开号：US08999985B2

  公开（公告）日：2015-04-07

  Disclosed are substituted phthalazin-1 (2H)-ones of the formula (IA), preparation processes and medical uses thereof, particularly related to the compositions containing the same and the uses thereof, more particularly related to their pharmaceutical use as inhibitors of PARP.

  本发明涉及一种式为（IA）的取代邻苯二酮类化合物，其制备方法和医药用途，特别涉及包含它们的组合物及其用途，更具体地涉及它们作为PARP抑制剂的药物用途。
• 4-[3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2<i>H</i>-phthalazin-1-one: A Novel Bioavailable Inhibitor of Poly(ADP-ribose) Polymerase-1
  作者：Keith A. Menear、Claire Adcock、Robert Boulter、Xiao-ling Cockcroft、Louise Copsey、Aaron Cranston、Krystyna J. Dillon、Jan Drzewiecki、Sheila Garman、Sylvie Gomez、Hashim Javaid、Frank Kerrigan、Charlotte Knights、Alan Lau、Vincent M. Loh、Ian T. W. Matthews、Stephen Moore、Mark J. O’Connor、Graeme C. M. Smith、Niall M. B. Martin

  DOI：10.1021/jm8001263

  日期：2008.10.23

  Poly(ADP-ribose) polymerase activation is an immediate cellular response to metabolic-, chemical-, or ionizing radiation-induced DNA damage and represents a new target for cancer therapy. In this article, we disclose a novel series of substituted 4-benzyl-2H-phthalazin-1-ones that possess high inhibitory enzyme and cellular potency for both PARP-1 and PARP-2. Optimized compounds from the series also demonstrate good pharmacokinetic profiles, oral bioavailability, and activity in vivo in an SW620 colorectal cancer xenograft model. 4-[3-(4-Cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one (KU-0059436, AZD2281) 47 is a single digit nanomolar inhibitor of both PARP-1 and PARP-2 that shows standalone activity against BRCA1-deficient breast cancer cell lines. Compound 47 is currently undergoing clinical development for the treatment of BRCA1- and BRCA2-defective cancers.
• Phthalazinones 2: Optimisation and synthesis of novel potent inhibitors of poly(ADP-ribose)polymerase
  作者：Xiao-ling Cockcroft、Krystyna J. Dillon、Lesley Dixon、Jan Drzewiecki、Frank Kerrigan、Vincent M. Loh、Niall M.B. Martin、Keith A. Menear、Graeme C.M. Smith

  DOI：10.1016/j.bmcl.2005.10.081

  日期：2006.2

  We have previously described the discovery of poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors based on a phthalazinone scaffold. Subsequent optimisation of inhibitory activity, metabolic stability and pharmacokinetic parameters has led to a novel series of meta-substituted 4-benzyl-2H-phthalazin-1-one PARP-1 inhibitors which retain low nM cellular activity and show good stability in vivo and efficacy in cell based models. (c) 2005 Elsevier Ltd. All rights reserved.
• HETEROCYCLIC DERIVATIVES, PREPARATION PROCESSES AND MEDICAL USES THEREOF
  申请人：Shanghai De Novo Pharmatech Co Ltd.

  公开号：EP2646428B1

  公开（公告）日：2016-06-01