4-(4-甲基-1-哌嗪基)-N-[1,4,5,6-四氢-5-(2-甲氧基-2-苯基乙酰基)吡咯并[3,4-c]吡唑-3-基]苯甲酰胺 | 1044136-93-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 4-(4-甲基-1-哌嗪基)-N-[1,4,5,6-四氢-5-(2-甲氧基-2-苯基乙酰基)吡咯并[3,4-c]吡唑-3-基]苯甲酰胺
• 英文名称: danusertib
• 英文别名: N-(5-(2-methoxy-2-phenylacetyl)-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl)-4-(4-methylpiperazin-1-yl)benzamide；N-[5-(2-methoxy-2-phenylacetyl)-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide
• CAS: 1044136-93-7
• 化学式: C₂₆H₃₀N₆O₃
• 分子量: 474.563
• InChiKey: XKFTZKGMDDZMJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  93.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  DL-alpha-甲氧基苯乙酸 在 草酰氯 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 4-(4-甲基-1-哌嗪基)-N-[1,4,5,6-四氢-5-(2-甲氧基-2-苯基乙酰基)吡咯并[3,4-c]吡唑-3-基]苯甲酰胺
  参考文献：
  名称：

  The human Aurora kinase inhibitor danusertib is a lead compound for anti-trypanosomal drug discovery via target repurposing

  摘要：

  New drugs for neglected tropical diseases such as human African trypanosomiasis (HAT) are needed, yet drug discovery efforts are not often focused on this area due to cost. Target repurposing, achieved by the matching of essential parasite enzymes to those human enzymes that have been successfully inhibited by small molecule drugs, provides an attractive means by which new drug optimization programs can be pragmatically initiated. In this report we describe our results in repurposing an established class of human Aurora kinase inhibitors, typified by danusertib (1), which we have observed to be an inhibitor of trypanosomal Aurora kinase 1 (TbAUK1) and effective in parasite killing in vitro. Informed by homology modeling and docking, a series of analogs of I were prepared that explored the scope of the chemotype and provided a nearly 25-fold improvement in cellular selectivity for parasite cells over human cells. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.07.038

文献信息

• [EN] PROTEOLYSIS TARGETING CHIMERA COMPOUNDS AND METHODS OF PREPARING AND USING SAME<br/>[FR] COMPOSÉS CHIMÈRES DE CIBLAGE DE PROTÉOLYSE ET PROCÉDÉS DE PRÉPARATION ET D'UTILISATION DE CEUX-CI
  申请人：UNIV YALE

  公开号：WO2017079267A1

  公开（公告）日：2017-05-11

  The present invention includes novel compounds and methods for preventing or treating diseases associated with and/or caused by overexpression and/or uncontrolled activation of a tyrosine kinase in a subject in need thereof. In certain embodiments, the compounds of the present invention comprise a tyrosine kinase inhibitor, a linker and a ubiquitin ligase binder. The methods of the present invention comprise administering to the subject an pharmaceutically effective amount of at least one compound of the invention.

  本发明涉及新型化合物和方法，用于预防或治疗与主题需要的酪氨酸激酶过度表达和/或无控制激活相关和/或引起的疾病。在某些实施例中，本发明的化合物包括酪氨酸激酶抑制剂、连接剂和泛素连接酶结合剂。本发明的方法包括向主题给予本发明中至少一种化合物的药物有效量。
• CARBAMOYL DERIVATIVES OF BICYCLIC CARBONYLAMINO-PYRAZOLES AS PRODRUGS
  申请人：Pulici Maurizio

  公开号：US20110118278A1

  公开（公告）日：2011-05-19

  There are provided bicyclic carbonylamino-pyrazoles of formula (I), wherein the variables are as specified in the claims, for use as medicament, in particular for the treatment of diseases due to the malfunctioning of protein kinases (PKs), such as cancer, pharmaceutical compositions comprising such carbamoyl derivatives, and their use as prodrugs of therapeutically active agents. Method of treatment and some new bicyclic carbonylamino-pyrazoles are also object of the present invention.

  本发明提供了式(I)的双环羰基氨基吡唑化合物，其中变量如权利要求中所述，用作药物，特别是用于治疗由蛋白激酶（PKs）功能失调引起的疾病，如癌症，包含此类羰酰基衍生物的制药组合物，并将其用作治疗活性剂的前药。本发明还涉及治疗方法和一些新的双环羰基氨基吡唑化合物。
• Methods of treating cholangiocarcinoma
  申请人：FOUNDATION MEDICINE, INC.

  公开号：US10980804B2

  公开（公告）日：2021-04-20

  Methods and compositions for treating cholangiocarcinoma.

  治疗胆管癌的方法和组合物。
• Fusion molecules and uses thereof
  申请人：FOUNDATION MEDICINE, INC.

  公开号：US11230589B2

  公开（公告）日：2022-01-25

  Novel fusion molecules and uses are disclosed.

  公开了新型融合分子及其用途。
• NOVEL FUSION MOLECULES AND USES THEREOF
  申请人：Foundation Medicine, Inc.

  公开号：EP2914622A2

  公开（公告）日：2015-09-09