N-{4-[4-(benzo[d][1,3]dioxol-5-yloxy)-2,6-dimethylphenyl]-thiazol-2-yl}pyridine-4-carboxamide | 1334921-14-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-{4-[4-(benzo[d][1,3]dioxol-5-yloxy)-2,6-dimethylphenyl]-thiazol-2-yl}pyridine-4-carboxamide
• 英文别名: N-(4-(4-(1,3-benzo[d]dioxol-5-yloxy)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide；N-(4-(4-(benzo[d][1,3]dioxol-5-yloxy)-2,6-dimethylphenyl)thiazol-2-yl)isonicotinamide；N-[4-[4-(1,3-benzodioxol-5-yloxy)-2,6-dimethylphenyl]-1,3-thiazol-2-yl]pyridine-4-carboxamide
• CAS: 1334921-14-0
• 化学式: C₂₄H₁₉N₃O₄S
• 分子量: 445.499
• InChiKey: WSHZTCRPQKJVTG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(4-氯-2,6-二甲基苯基)乙酮 在 4-二甲氨基吡啶 、 potassium phosphate 、 palladium diacetate 、 tetra-N-butylammonium tribromide 、 2-二-叔丁膦基-2',4',6'-三异丙基联苯 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 16.33h， 生成 N-{4-[4-(benzo[d][1,3]dioxol-5-yloxy)-2,6-dimethylphenyl]-thiazol-2-yl}pyridine-4-carboxamide
  参考文献：
  名称：

  Discovery of 4-Aryl-N-arylcarbonyl-2-aminothiazoles as Hec1/Nek2 Inhibitors. Part I: Optimization of in Vitro Potencies and Pharmacokinetic Properties

  摘要：

  A series of 4-aryl-N-arylcarbonyl-2-aminothiazoles of scaffold 4 was designed and synthesized as Hec1/Nek2 inhibitors. Structural optimization of 4 led to compound S 32 bearing C-4' 4-methoxyphenoxy and 4-(o-fluoropyridyl)-carbonyl groups that showed low nanomolar in vitro antiproliferative activity (IC50: 16.3-42.7 nM), high intravenous AUC (64.9 mu M.h, 2.0 mg/kg) in SD rats, and significant in vivo antitumor activity (T/C = 32%, 20 mg/kg, IV) in mice bearing human MDA-MB-231 xenografts. Cell responses resulting from Hec1/Nek2 inhibition were observed in cells treated with 32, including a reduced level of Hec1 coimmunoprecipitated with Nek2, degradation of Nek2, mitotic abnormalities, and apoptosis. Compound 32 showed selectivity toward cancer cells over normal phenotype cells and was inactive in a [H-3]astemizole competitive binding assay for hERG liability screening. Therefore, 32 is as a good lead toward the discovery of a preclinical candidate targeting Hec1/Nek2 interaction.

  DOI：

  10.1021/jm401990s

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。
• [EN] IMPROVED MODULATORS OF HEC1 ACTIVITY AND METHODS THEREFOR<br/>[FR] MODULATEURS AMÉLIORÉS DE L'ACTIVITÉ HEC1 ET PROCÉDÉS ASSOCIÉS
  申请人：TAIVEX THERAPEUTICS CORP

  公开号：WO2013082324A1

  公开（公告）日：2013-06-06

  Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Such compounds disrupt Nek2/Hec1 binding and may be useful as chemotherapeutic agents 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。这些化合物破坏了Nek2/Hec1的结合，并可能作为抗肿瘤疾病的化疗药物有用。
• MODULATORS OF HEC1 ACTIVITY AND METHODS THEREFOR
  申请人：HUANG Jiann-Jyh

  公开号：US20130190312A1

  公开（公告）日：2013-07-25

  Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Such compounds disrupt Nek2/Hec1 binding and may be useful as chemotherapeutic agents for neoplastic diseases.

  提供了调节Hec1/Nek2相互作用的化合物、组合物和方法。这些化合物破坏Nek2/Hec1结合，可能作为肿瘤治疗药物有用。
• Modulators of HEC1 activity and methods therefor
  申请人：TAIVEX THERAPEUTICS CORPORATION

  公开号：US10588909B2

  公开（公告）日：2020-03-17

  Compounds, compositions, and methods for modulation of Hec1/Nek2 interaction are provided. Such compounds disrupt Nek2/Hec1 binding and may be useful as chemotherapeutic agents for neoplastic diseases.

  本文提供了调节 Hec1/Nek2 相互作用的化合物、组合物和方法。这些化合物能破坏 Nek2/Hec1 的结合，可用作肿瘤疾病的化疗药物。
• IMPROVED MODULATORS OF HEC1 ACTIVITY AND METHODS THEREFOR
  申请人：Taivex Therapeutics Corporation

  公开号：EP2785714A1

  公开（公告）日：2014-10-08