2-(((1r,4r)-4-hydroxycyclohexyl)amino)-4-(3 ,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzamide | 908116-30-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(((1r,4r)-4-hydroxycyclohexyl)amino)-4-(3 ,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzamide
• 英文别名: 2-((4-hydroxycyclohexyl)amino)-4-(3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzamide；2-[(4-Hydroxycyclohexyl)amino]-4-(3,6,6-trimethyl-4-oxo-5,7-dihydroindazol-1-yl)benzamide
• CAS: 908116-30-3
• 化学式: C₂₃H₃₀N₄O₃
• 分子量: 410.516
• InChiKey: FMOSGTTYAFQMSD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(((1r,4r)-4-hydroxycyclohexyl)amino)-4-(3 ,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzamide 在 4-二甲氨基吡啶 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以73%的产率得到BJ-B11
  参考文献：
  名称：

  Synthesis and in vitro anti-HSV-1 activity of a novel Hsp90 inhibitor BJ-B11

  摘要：

  In this study, a novel Hsp90 inhibitor BJ-B11, was synthesized and evaluated for in vitro antiviral activity against several viruses. Possible anti-HSV-1 mechanisms were also investigated. BJ-B11 displayed no antiviral activity against coxsackievirus B-3 (CVB3), human respiratory syncytial virus (RSV) and influenza virus (H1N1), but exhibited potent anti-HSV-1 and HSV-2 activity with EC50 values of 0.42 +/- 0.18 mu M and 0.60 +/- 0.21 mu M, respectively. Additionally, the inhibitory effects of BJ-B11 against HSV-1 were likely to be introduced at early stage of infection. Our results indicate that BJ-B11 with alternative mechanisms of action is potent as an anti-HSV clinical trial candidate. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.098
• 作为产物：
  描述：

  4-hydrazino-2-(4-hydroxy-cyclohexylamino)-benzonitrile 在 双氧水 、 溶剂黄146 、 potassium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 生成 2-(((1r,4r)-4-hydroxycyclohexyl)amino)-4-(3 ,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indazol-1-yl)benzamide
  参考文献：
  名称：

  Synthesis and in vitro anti-HSV-1 activity of a novel Hsp90 inhibitor BJ-B11

  摘要：

  In this study, a novel Hsp90 inhibitor BJ-B11, was synthesized and evaluated for in vitro antiviral activity against several viruses. Possible anti-HSV-1 mechanisms were also investigated. BJ-B11 displayed no antiviral activity against coxsackievirus B-3 (CVB3), human respiratory syncytial virus (RSV) and influenza virus (H1N1), but exhibited potent anti-HSV-1 and HSV-2 activity with EC50 values of 0.42 +/- 0.18 mu M and 0.60 +/- 0.21 mu M, respectively. Additionally, the inhibitory effects of BJ-B11 against HSV-1 were likely to be introduced at early stage of infection. Our results indicate that BJ-B11 with alternative mechanisms of action is potent as an anti-HSV clinical trial candidate. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.01.098

文献信息

• [EN] COMPOUNDS AND METHODS FOR TARGETING HSP90<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LE CIBLAGE DE HSP90
  申请人：UNIV DUKE

  公开号：WO2014025395A1

  公开（公告）日：2014-02-13

  Described herein are compounds that may selectively bind to Hsp90, methods of using the compounds, and kits including the compounds. The compounds may include detection moieties such as fluorophores that may allow for selective detection of Hsp90 in a sample.

  本文描述了可能选择性结合到Hsp90的化合物，使用这些化合物的方法，以及包括这些化合物的试剂盒。这些化合物可能包括检测基团，如荧光团，可以允许在样本中选择性地检测Hsp90。
• NOVEL INHIBITORS OF TRANSFORMING GROWTH FACTOR KINASE AND METHODS OF USE THEREOF
  申请人：Duke University

  公开号：US20180105500A1

  公开（公告）日：2018-04-19

  The present invention provides novel inhibitors of TAK1 and methods of using such compounds to treat various diseases.

  本发明提供了新型TAK1抑制剂以及使用这类化合物治疗各种疾病的方法。
• Discovery of Novel 2-Aminobenzamide Inhibitors of Heat Shock Protein 90 as Potent, Selective and Orally Active Antitumor Agents
  作者：Kenneth H. Huang、James M. Veal、R. Patrick Fadden、John W. Rice、Jeron Eaves、Jon-Paul Strachan、Amy F. Barabasz、Briana E. Foley、Thomas E. Barta、Wei Ma、Melanie A. Silinski、Mei Hu、Jeffrey M. Partridge、Anisa Scott、Laura G. DuBois、Tiffany Freed、Paul M. Steed、Andy J. Ommen、Emilie D. Smith、Philip F. Hughes、Angela R. Woodward、Gunnar J. Hanson、W. Stephen McCall、Christopher J. Markworth、Lindsay Hinkley、Matthew Jenks、Lifeng Geng、Meredith Lewis、James Otto、Bert Pronk、Katleen Verleysen、Steven E. Hall

  DOI：10.1021/jm900230j

  日期：2009.7.23

  roxycyclohexyl)amino]benzamide (SNX-2112, 9) was identified as highly selective and potent (IC50 Her2 = 11 nM, HT-29 = 3 nM); its prodrug amino-acetic acid 4-[2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-phenylamino]-cyclohexyl ester methanesulfonate (SNX-5422, 10) was orally bioavailable and efficacious in a broad range of xenograft tumor models (e.g. 67% growth

  从无偏筛选中开发了一类新型的热休克蛋白90（Hsp90）抑制剂，以鉴定多种化合物文库的蛋白靶标。这些吲哚-4-酮和吲哚-4-酮衍生的2-氨基苯甲酰胺对Hsp90具有很强的结合亲和力，优化的类似物在多种癌细胞系中均表现出纳摩尔级的抗增殖活性。用抑制剂处理后，细胞中的热休克蛋白70（Hsp70）诱导和特定的客体蛋白降解支持Hsp90抑制作为作用机理。所选成员化合物的计算化学和X射线晶体学分析清楚地定义了蛋白质与抑制剂的相互作用，并有助于类似物的设计。4- [6,6-二甲基-4-氧代-3-（三氟甲基）-4,5,6,7-四氢-1 H-吲唑-1-基] -2 - [（反式-4-羟基环己基）氨基]苯甲酰胺（SNX-2112，9）被确定为高度选择性的和有效（IC 50的Her2 = 11纳米，HT-29 = 3 nM）的; 其前药氨基乙酸4- [2-氨基甲酰基-5-（6,6-二甲基-4-氧代-3-三氟甲基-4
• Cyclohexylamino Benzene, Pyridine, and Pyridazine Derivatives
  申请人：Huang He Kenneth

  公开号：US20070207984A1

  公开（公告）日：2007-09-06

  Disclosed are compounds and pharmaceutically acceptable salts of Formula (I), wherein Q 1 , Q 2 , R N , R 1 , R 2 , R 5 , R 6 , R 7 , R 8 , X 1 , X 2 , X 4 , and Y are as defined herein. Compounds of Formula (I) are useful in the treatment of diseases and/or conditions related to cell proliferation, such as cancer, inflammation, arthritis, angiogenesis, or the like. Also disclosed are pharmaceutical compositions comprising compounds of the invention and methods of treating the aforementioned conditions using such compounds.

  本文披露了公式(I)的化合物和药用盐，其中Q1、Q2、RN、R1、R2、R5、R6、R7、R8、X1、X2、X4和Y如本文所定义。公式(I)的化合物在治疗与细胞增殖相关的疾病和/或症状方面具有用途，例如癌症、炎症、关节炎、血管生成等。还披露了包括本发明的化合物的药物组合物以及使用这些化合物治疗上述疾病的方法。
• 一种合成四氢吲唑化合物的方法
  申请人：广州暨南生物医药研究开发基地有限公司

  公开号：CN109796409A

  公开（公告）日：2019-05-24

  本发明属于药物合成技术领域，具体涉及一种合成四氢吲唑化合物的方法。该合成方法包括5,5‑二甲基‑2‑乙酰基‑1,3‑环己二酮的合成、2‑氟‑4‑肼基苯甲腈的合成、2‑氟‑4‑(3,6,6‑三甲基‑4‑氧‑4,5,6,7‑四氢‑1H‑吲唑‑1‑)苯甲腈的合成、2‑(4‑羟基环己氨基)‑4‑(3,6,6‑三甲基‑4‑氧‑4,5,6,7‑四氢‑1H‑吲唑‑1‑)苯甲腈的合成和、2‑(4‑羟基环己氨基)‑4‑(3,6,6‑三甲基‑4‑氧‑4,5,6,7‑四氢‑1H‑吲唑‑1‑)苯甲酰胺的合成。中间物2‑氟‑4‑(3,6,6‑三甲基‑4‑氧‑4,5,6,7‑四氢‑1H‑吲唑‑1‑)苯甲腈的产率高达93％，纯度高，使制备得到的四氢吲唑化合物纯度高，适合大批量生产。