N-[4-(2,4,6-三甲基苯基)-2-噻唑基]苯甲酰胺 | 1001753-24-7

• 物质功能分类: 生物化工 - 抑制剂 - 细胞骨架(Cytoskeletal Signaling)
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[4-(2,4,6-三甲基苯基)-2-噻唑基]苯甲酰胺
• 英文名称: INH-6
• 英文别名: N-(4-mesitylthiazol-2-yl)benzamide；N-[4-(2,4,6-trimethylphenyl)-1,3-thiazol-2-yl]benzamide
• CAS: 1001753-24-7
• 化学式: C₁₉H₁₈N₂OS
• 分子量: 322.431
• InChiKey: WCZLNJTXHZPHLM-UHFFFAOYSA-N

物化性质

• 熔点：
  192-193 °C
• 密度：
  1.216±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO 中≥32.2 mg/mL；不溶于水； ≥3.55 mg/mL，乙醇溶液，温和加热和超声波

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  70.2
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

INH6 是一种强效的 Hec1 抑制剂，能够特异性地破坏 Hec1/Nek2 的相互作用，并导致染色体排列异常。

体外研究

INH6 能有效作用于 Hec1/Nek2 复合物，使其降解。在 MDA-MB-231、MDA-MB-468、HeLa 和 K562 细胞系中，其表现出有效的细胞杀伤活性，IC50 值分别为 1.7 μM、2.1 μM、2.4 μM 和 2.5 μM。此外，INH6 还会引起 HeLa 细胞中的有丝分裂异常，并诱导细胞凋亡。

靶点

• IC50: HeLa (2.4 μM), MDA-MB-231 (1.7 μM), MDA-MB-468 (2.1 μM), K562 (2.5 μM)

反应信息

• 作为反应物：
  描述：

  1-azido-2-(2-(2-(2-iodoethoxy)ethoxy)ethoxy)ethane 、 N-[4-(2,4,6-三甲基苯基)-2-噻唑基]苯甲酰胺 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 以66%的产率得到N-(2-{2-[2-(2-azido-ethoxy)-ethoxy]-ethoxy}-ethyl)-N-[4-(2,4,6-trimethyl-phenyl)-thiazol-2-yl]benzamide
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Series of Novel Inhibitor of Nek2/Hec1 Analogues

  摘要：

  High expression in cancer 1 (Hec1) is an oncogene overly expressed in many human cancers. Small molecule inhibitor of Nek2/Hcc1 (INH) targeting the Heel and its regulator, Nek2, in the mitotic pathway, was identified to inactivate Hec1/Nek2 function mediated by protein degradation that subsequently leads to chromosome mis-segregation and cell death. To further improve the efficacy of INH, a series of INH analogues were designed, synthesized, and evaluated. Among these 33 newly synthesized analogues, three of them, 6, 13, and 21, have 6-8 fold more potent cell killing activity than the previous lead compound INH1. Compounds 6 and 21 were chosen for analyzing the underlying action mechanism. They target directly the Hec1/Nek2 pathway and cause chromosome mis-alignment as well as cell death, a mechanism similar to that of INH1, This initial exploration of structural/functional relationship of INH may advance the progress for developing clinically applicable INH analogue.

  DOI：

  10.1021/jm8015969
• 作为产物：
  描述：

  4-(2,4,6-三甲基苯基)-2-氨基噻唑 、 苯甲酰氯 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.5h， 以31%的产率得到N-[4-(2,4,6-三甲基苯基)-2-噻唑基]苯甲酰胺
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Series of Novel Inhibitor of Nek2/Hec1 Analogues

  摘要：

  High expression in cancer 1 (Hec1) is an oncogene overly expressed in many human cancers. Small molecule inhibitor of Nek2/Hcc1 (INH) targeting the Heel and its regulator, Nek2, in the mitotic pathway, was identified to inactivate Hec1/Nek2 function mediated by protein degradation that subsequently leads to chromosome mis-segregation and cell death. To further improve the efficacy of INH, a series of INH analogues were designed, synthesized, and evaluated. Among these 33 newly synthesized analogues, three of them, 6, 13, and 21, have 6-8 fold more potent cell killing activity than the previous lead compound INH1. Compounds 6 and 21 were chosen for analyzing the underlying action mechanism. They target directly the Hec1/Nek2 pathway and cause chromosome mis-alignment as well as cell death, a mechanism similar to that of INH1, This initial exploration of structural/functional relationship of INH may advance the progress for developing clinically applicable INH analogue.

  DOI：

  10.1021/jm8015969

文献信息

• Modulators Of HEC1 Activity And Methods Therefor
  申请人：Lau Johnson

  公开号：US20110230486A1

  公开（公告）日：2011-09-22

  Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Especially preferred compounds disrupt Nek2/Hec1 binding and are therefore useful as chemotherapeutic agent for neoplastic diseases.

  提供了用于调节Hec1/Nek2相互作用的化合物、组合物和方法。特别偏爱的化合物会破坏Nek2/Hec1的结合，因此可用作肿瘤疾病的化疗药物。
• MODULATORS OF HEC1 ACTIVITY AND METHODS THEREFOR
  申请人：Taivex Therapeutics, Inc.

  公开号：US20150057281A1

  公开（公告）日：2015-02-26

  Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Especially preferred compounds disrupt Nek2/Hec1 binding and are therefore useful as chemotherapeutic agent for neoplastic diseases.

  提供了调节Hec1/Nek2相互作用的化合物、组合物和方法。特别优选的化合物破坏Nek2/Hec1结合并因此可用作肿瘤疾病的化疗药物。
• COMBINATIONS OF THERAPEUTIC AGENTS FOR TREATING UVEAL MELANOMA
  申请人：Universiteit Gent

  公开号：US20220218734A1

  公开（公告）日：2022-07-14

  A combination of therapeutic compounds for treating cancer. More specifically, the present discloses that inhibition of the long non-coding RNA known as SAMMSON in combination with at least one of FDA-approved, anti-cancer compounds results in killing of uveal melanoma cells in a synergistic manner.
• US8946268B2
  申请人：——

  公开号：US8946268B2

  公开（公告）日：2015-02-03
• US9409902B2
  申请人：——

  公开号：US9409902B2

  公开（公告）日：2016-08-09