Bromo-2-piperazin-1-ylpyrimidine | 1209528-23-3

• 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: Bromo-2-piperazin-1-ylpyrimidine
• 英文别名: 4-Bromo-2-piperazin-1-ylpyrimidine
• CAS: 1209528-23-3
• 化学式: C₈H₁₁BrN₄
• 分子量: 243.106
• InChiKey: UPYVVYJYSOBJAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Bromo-2-piperazin-1-ylpyrimidine 、 2,3-difluoro-5-((4-oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 以47%的产率得到4-(3-(4-(4-bromopyrimidin-2-yl)piperazine-1-carbonyl)-4,5-difluorobenzyl)phthalazin-1(2H)-one
  参考文献：
  名称：

  Discovery, mechanism and metabolism studies of 2,3-difluorophenyl-linker-containing PARP1 inhibitors with enhanced in vivo efficacy for cancer therapy

  摘要：

  Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially breast and ovarian cancers, and tumor cell lines deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition. In this study, with the help of molecular docking, we identified a novel series of 2,3-difluorophenyl-linker analogues (15-54) derived from olaparib (1) as PARPI inhibitors. Lead optimization led to the identification of 47, which showed high selectivity and high potency against PARP1 enzyme (IC50 = 13 nM), V-C8 cells (IC50 = 0.003 nM), Capan-1 cells (IC50 = 7.1 nM) and MDA-MB-436 cells (IC50 = 0.2 nM). Compound 47 had more potent PARPI-DNA trapping and double-strand breaks (DSBs)-induction activities than 1 and induced G2/M arrest and caspase-dependent apoptosis. Compound 47 (50 mg/kg, 94.2%) had a more beneficial effect on tumor growth inhibition than 1 (100 mg/kg, 65.0%) in a BRCA1-mutated xenograft model and significantly inhibited tumor growth (40 mg/kg, 48.1%) in a BRCA2-mutated xenograft model, with no negative influence on the body weight of the mice. Collectively, these data demonstrated that 47 might be an excellent drug candidate for the treatment of cancer, especially for BRCA-deficient tumors. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.053

文献信息

• [EN] DEUTERATED TANDOSPIRONE DERIVATIVES AS 5-HT1A RECEPTOR AGONISTS<br/>[FR] DÉRIVÉS DEUTÉRÉS DE TANDOSPIRONE CONVENANT COMME AGONISTES DU RÉCEPTEUR 5-HT1A
  申请人：CONRIG PHARMA APS

  公开号：WO2012016569A1

  公开（公告）日：2012-02-09

  The present invention relates to new deuterated derivatives of serotonin 5-HT1A receptor agonists of formula 1 and in particular to compositions and methods for therapeutic use.

  本发明涉及公式1的新的氘代衍生物，特别是用于治疗的组合物和方法。
• DEUTERATED 5-HT1A RECEPTOR AGONISTS
  申请人：Hansen John Bondo

  公开号：US20130303497A1

  公开（公告）日：2013-11-14

  The present invention relates to new deuterated derivatives of serotonin 5-HT1A receptor agonists of formula 1 and in particular to compositions and methods for therapeutic use.

  本发明涉及公式1的新的氘代衍生物，特别是涉及用于治疗的组合物和方法。
• DEUTERATED TANDOSPIRONE DERIVATIVES AS 5-HT1A RECEPTOR AGONISTS
  申请人：Conrig Pharma ApS

  公开号：EP2601187A1

  公开（公告）日：2013-06-12