2-bromo-5-(2-methoxyethoxy)pyrazine | 1351523-79-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-bromo-5-(2-methoxyethoxy)pyrazine
• 英文别名: 2-Bromo-5-(2-methoxyethoxy)pyrazine
• CAS: 1351523-79-9
• 化学式: C₇H₉BrN₂O₂
• 分子量: 233.065
• InChiKey: VLRPMRIKPZZZMT-UHFFFAOYSA-N

物化性质

• 沸点：
  276.4±40.0 °C(Predicted)
• 密度：
  1.499±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-bromo-5-(2-methoxyethoxy)pyrazine 在 copper(l) iodide 、 sodium hydrosulfide hydrate 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 N-(4-{4-(5-(2-methoxyethoxy)pyrazin-2-ylsulfonyl)-2,6-dimethylphenyl}thiazol-2-yl)isonicotinamide
  参考文献：
  名称：

  [EN] IMPROVED MODULATORS OF HEC1 ACTIVITY AND METHODS THEREFOR
  [FR] MODULATEURS AMÉLIORÉS DE L'ACTIVITÉ HEC1 ET PROCÉDÉS ASSOCIÉS

  摘要：

  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。

  公开号：

  WO2013082324A1
• 作为产物：
  描述：

  2,5-二溴吡嗪 、 乙二醇甲醚 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 以88%的产率得到2-bromo-5-(2-methoxyethoxy)pyrazine
  参考文献：
  名称：

  [EN] IMPROVED MODULATORS OF HEC1 ACTIVITY AND METHODS THEREFOR
  [FR] MODULATEURS AMÉLIORÉS DE L'ACTIVITÉ HEC1 ET PROCÉDÉS ASSOCIÉS

  摘要：

  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。

  公开号：

  WO2013082324A1

文献信息

• [EN] NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITION AND METHODS FOR USE IN TREATING METABOLIC DISORDERS<br/>[FR] NOUVEAUX COMPOSÉS, LEURS COMPOSITIONS PHARMACEUTIQUES ET MÉTHODES D'UTILISATION DANS LE TRAITEMENT DE TROUBLES MÉTABOLIQUES
  申请人：EUROSCREEN SA

  公开号：WO2011151434A1

  公开（公告）日：2011-12-08

  The present invention is directed to novel compounds of formula (I) and their use in treating metabolic diseases.

  本发明涉及公式（I）的新化合物及其在治疗代谢性疾病中的应用。
• 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：US08999983B2

  公开（公告）日：2015-04-07

  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，可能作为治疗肿瘤疾病的化疗药物有用。
• 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。
• Discovery of T-1101 tosylate as a first-in-class clinical candidate for Hec1/Nek2 inhibition in cancer therapy
  作者：Shih-Hsien Chuang、Ying-Shuan E. Lee、Lynn Y.L. Huang、Chi-Kuan Chen、Chun-Liang Lai、Yu-Hsiang Lin、Ju-Ying Yang、Sheng-Chuan Yang、Lien-Hsiang Chang、Ching-Hui Chen、Chia-Wei Liu、Her-Sheng Lin、Yi-Ru Lee、Kuan Pin Huang、Kuo Chu Fu、Hsueh-Min Jen、Jun-Yu Lai、Pei-Shiou Jian、Yu-Chuan Wang、Wen-Yun Hsueh、Pei-Yi Tsai、Wan-Hua Hong、Chia-Chi Chang、Diana ZC. Wu、Jinn Wu、Meng-Hsin Chen、Kuo-Ming Yu、Ching Yuh Chern、Jia-Ming Chang、Johnson Y.N. Lau、Jiann-Jyh Huang

  DOI：10.1016/j.ejmech.2020.112118

  日期：2020.4

  Highly expressed in cancer 1 (Hec1) plays an essential role in mitosis and is correlated with cancer formation, progression, and survival. Phosphorylation of Hec1 by Nek2 kinase is essential for its mitotic function, thus any disruption of Hec1/Nek2 protein-protein interaction has potential for cancer therapy. We have developed T-1101 tosylate (9j tosylate, 9j formerly known as TAI-95), optimized from 4-aryl-N-pyridinylcarbonyl-2-aminothiazole of scaffold 9 by introducing various C-4' substituents to enhance potency and water solubility, as a first-in-class oral clinical candidate for Hec1 inhibition with potential for cancer therapy. T-1101 has good oral absorption, along with potent in vitro antiproliferative activity (IC50: 14.8-21.5 nM). It can achieve high concentrations in Huh-7 and MDA-MB-231 tumor tissues, and showed promise in antitumor activity in mice bearing human tumor xenografts of liver cancer (Huh-7), as well as of breast cancer (BT474, MDA-MB-231, and MCF7) with oral administration. Oral co-administration of T-1101 halved the dose of sorafenib (25 mg/kg to 12.5 mg/kg) required to exhibit comparable in vivo activity towards Huh-7 xenografts. Cellular events resulting from Hec1/Nek2 inhibition with T-1101 treatment include Nek2 degradation, chromosomal misalignment, and apoptotic cell death. A combination of T-1101 with either of doxorubicin, paclitaxel, and topotecan in select cancer cells also resulted in synergistic effects. Inactivity of T-1101 on non-cancerous cells, a panel of kinases, and hERG demonstrates cancer specificity, target specificity, and cardiac safety, respectively. Subsequent salt screening showed that T-1101 tosylate has good oral AUC (62.5 mu M.h), bioavailability (F = 77.4%), and thermal stability. T-1101 tosylate is currently in phase I clinical trials as an orally administered drug for cancer therapy. (c) 2020 Elsevier Masson SAS. All rights reserved.