2-(1-甲基-1H-吡唑-4-基)-3-氧代丙腈 | 1039364-93-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-(1-甲基-1H-吡唑-4-基)-3-氧代丙腈
• 英文名称: 2-(1-Methyl-1H-pyrazol-4-YL)-3-oxopropanenitrile
• 英文别名: 2-(1-methylpyrazol-4-yl)-3-oxopropanenitrile
• CAS: 1039364-93-6
• 化学式: C₇H₇N₃O
• 分子量: 149.152
• InChiKey: OLHJDZJUPYTURE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  58.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(1-甲基-1H-吡唑-4-基)-3-氧代丙腈 在 N-溴代丁二酰亚胺(NBS) 、 盐酸肼 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 6-溴-3-(1-甲基-1H-吡唑-4-基)-5-(3R)-3-哌啶基吡唑并[1,5-A]嘧啶-7-胺
  参考文献：
  名称：

  CHK1抑制剂MK-8776（SCH 900776）的收敛制剂

  摘要：

  这封信描述了向CHK1抑制剂MK-8776汇聚，高效途径的发展。该合成方法依赖于双吡唑加合物10与光学纯的β-酮腈9的环化，以一步构建吡唑并[1，5- a ]嘧啶骨架。

  DOI：

  10.1016/j.tetlet.2016.04.102
• 作为产物：
  描述：

  1-甲基-1H-吡唑-4-甲醛 在 potassium tert-butylate 作用下， 以 乙二醇二甲醚 为溶剂， 生成 2-(1-甲基-1H-吡唑-4-基)-3-氧代丙腈
  参考文献：
  名称：

  CHK1抑制剂MK-8776（SCH 900776）的收敛制剂

  摘要：

  这封信描述了向CHK1抑制剂MK-8776汇聚，高效途径的发展。该合成方法依赖于双吡唑加合物10与光学纯的β-酮腈9的环化，以一步构建吡唑并[1，5- a ]嘧啶骨架。

  DOI：

  10.1016/j.tetlet.2016.04.102

文献信息

• [EN] COMPOSITIONS AND METHODS FOR TREATING CANCER<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DU CANCER
  申请人：MERCK SHARP & DOHME

  公开号：WO2013039854A1

  公开（公告）日：2013-03-21

  The instant invention provides a method of treating a cancer, selected from the group consisting of breast cancer, melanoma, colorectal cancer, non-small cell lung cancer and ovarian cancer, by administering a combination of a WEE1 inhibitor and a CHK1 inhibitor, wherein the WEE1 inhibitor is MK-1775 or a pharmaceutically acceptable salt thereof, or MK-3652 or a pharmaceutically acceptable salt thereof, and the CHK1 inhibitor is MK-8776 or a pharmaceutically acceptable salt thereof, or SCH900444 or a pharmaceutically acceptable salt thereof.

  该瞬时发明提供了一种治疗癌症的方法，所述癌症包括乳腺癌、黑色素瘤、结直肠癌、非小细胞肺癌和卵巢癌，通过给予一种WEE1抑制剂和一种CHK1抑制剂的组合，其中WEE1抑制剂为MK-1775或其药用盐，或MK-3652或其药用盐，CHK1抑制剂为MK-8776或其药用盐，或SCH900444或其药用盐。
• [EN] COMPOSITIONS AND METHODS FOR TREATING CANCER<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE TRAITEMENT DU CANCER
  申请人：MERCK SHARP & DOHME

  公开号：WO2014062454A1

  公开（公告）日：2014-04-24

  The instant invention relates to methods for the treatment of neuroblastoma by administering a combination of a WEE1 inhibitor and a CHK1 inhibitor, wherein the WEE1 inhibitor is WEE1-1 or a pharmaceutically acceptable salt thereof, or WEE1-2 or a pharmaceutically acceptable salt thereof, and the CHK1 inhibitor is CHK1-1 or a pharmaceutically acceptable salt thereof. In another embodiment, the invention relates to a method for treating a neuroblastoma patient, comprising administering a WEE1 inhibitor and a CHK1 inhibitor, wherein the cancer cells of said patient to be treated are characterized by amplified expression levels of MYCN.

  该瞬时发明涉及通过给予一种WEE1抑制剂和一种CHK1抑制剂的组合来治疗神经母细胞瘤的方法，其中WEE1抑制剂是WEE1-1或其药学上可接受的盐，或者是WEE1-2或其药学上可接受的盐，而CHK1抑制剂是CHK1-1或其药学上可接受的盐。在另一实施方案中，该发明涉及一种治疗神经母细胞瘤患者的方法，包括给予WEE1抑制剂和CHK1抑制剂，其中待治疗患者的癌细胞具有MYCN基因表达水平增高的特征。
• 7-Aminopyrazolo[1,5-<i>a</i>]pyrimidines as Potent Multitargeted Receptor Tyrosine Kinase Inhibitors
  作者：Robin R. Frey、Michael L. Curtin、Daniel H. Albert、Keith B. Glaser、Lori J. Pease、Niru B. Soni、Jennifer J. Bouska、David Reuter、Kent D. Stewart、Patrick Marcotte、Gail Bukofzer、Junling Li、Steven K. Davidsen、Michael R. Michaelides

  DOI：10.1021/jm701397k

  日期：2008.7

  7-Aminopyrazolo[1,5-a]pyrimidine urea receptor tyrosine kinase inhibitors have been discovered. Investigation of structure-activity relationships of the pyrazolo[1,5-a]pyrimidine nucleus led to a series of 6-(4-N,N'-diphenyl)ureas that potently inhibited a panel of vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) kinases. Several of these compounds, such as 34a, are potent inhibitors of kinase insert domain-containing receptor tyrosine kinase (KDR) both enzymatically (< 10 nM) and cellularly (< 10 nM). In addition, compound 34a possesses a favorable pharmacokinetic profile and demonstrates efficacy in the estradiol-induced murine uterine edema (UE) model (ED(50) = 1.4 mg/kg).
• Discovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: A template-based approach—Part 2
  作者：Marc Labroli、Kamil Paruch、Michael P. Dwyer、Carmen Alvarez、Kartik Keertikar、Cory Poker、Randall Rossman、Jose S. Duca、Thierry O. Fischmann、Vincent Madison、David Parry、Nicole Davis、Wolfgang Seghezzi、Derek Wiswell、Timothy J. Guzi

  DOI：10.1016/j.bmcl.2010.10.114

  日期：2011.1

  Previous efforts by our group have established pyrazolo[1,5-a]pyrimidine as a viable core for the development of potent and selective CDK inhibitors. As part of an effort to utilize the pyrazolo[1,5-a]pyrimidine core as a template for the design and synthesis of potent and selective kinase inhibitors, we focused on a key regulator in the cell cycle progression, CHK1. Continued SAR development of the pyrazolo [1,5-a]pyrimidine core at the C5 and C6 positions, in conjunction with previously disclosed SAR at the C3 and C7 positions, led to the discovery of potent and selective CHK1 inhibitors. (c) 2010 Elsevier Ltd. All rights reserved.
• WO2008/153870
  申请人：——

  公开号：——

  公开（公告）日：——