1-bromo-2-chloro(²H₄)ethane | 1219795-52-4

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 卤代烷
• 英文名称: 1-bromo-2-chloro(²H₄)ethane
• 英文别名: 1-Bromo-2-chloroethane-d4；1-bromo-2-chloro-1,1,2,2-tetradeuterioethane
• CAS: 1219795-52-4
• 化学式: C₂H₄BrCl
• 分子量: 147.379
• InChiKey: IBYHHJPAARCAIE-LNLMKGTHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  4
• 可旋转键数：
  1
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

反应信息

• 作为反应物：
  描述：

  4-氯喹唑啉-6,7-二醇 、 1-bromo-2-chloro(²H₄)ethane 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 19.08h， 以49%的产率得到4-chloro(7,7,8,8-²H₄)-7,8-dihydro[1,4]dioxino[2,3-g]quinazoline
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR TREATING CANCER
  [FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DU CANCER

  摘要：

  本公开涉及能够穿透血脑屏障以调节EGFR酪氨酸激酶活性的化合物。该公开进一步涉及治疗胶质母细胞瘤和其他EGFR介导的癌症的方法。该公开还涉及治疗已确定在抑制剂存在下具有改变葡萄糖代谢的胶质母细胞瘤和其他EGFR介导的癌症的方法。本公开还提供了向受试者施用葡萄糖代谢抑制剂和细胞质p53稳定剂的方法。

  公开号：

  WO2019067543A1

文献信息

• [EN] 1,3-SUBSTITUED PYRAZOLE COMPOUNDS USEFUL FOR REDUCTION OF VERY LONG CHAIN FATTY ACIC LEVELS<br/>[FR] COMPOSÉS PYRAZOLE 1,3-SUBSTITUÉS UTILES POUR LA RÉDUCTION DE NIVEAUX D'ACIDES GRAS À CHAÎNE TRÈS LONGUE
  申请人：VERTEX PHARMA

  公开号：WO2018107056A1

  公开（公告）日：2018-06-14

  Disclosed are chemical entities which are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein Formula (I) has the structure: R1a, R1b, R2, R3, R4a, R4b and Y are as defined herein. These chemical entities are useful for reduction of very long chain fatty acid levels. These chemical entities and pharmaceutically acceptable compositions comprising such chemical entities can be useful for treating various diseases, disorders and conditions, such as adrenoleukodystrophy (ALD).

  揭示了化学实体，它们是具有式（I）的化合物及其药学上可接受的盐，其中式（I）具有结构：R1a，R1b，R2，R3，R4a，R4b和Y如本文所定义。这些化学实体对于降低非常长链脂肪酸水平是有用的。这些化学实体和包括这些化学实体的药学上可接受的组合物可用于治疗各种疾病、疾病和症状，如肾上腺白质脑白质营养不良（ALD）。
• WO2020/190765
  申请人：——

  公开号：——

  公开（公告）日：——
• Development of a Potent Brain-Penetrant EGFR Tyrosine Kinase Inhibitor against Malignant Brain Tumors
  作者：Jonathan E. Tsang、Lorenz M. Urner、Gyudong Kim、Kingsley Chow、Lynn Baufeld、Kym Faull、Timothy F. Cloughesy、Peter M. Clark、Michael E. Jung、David A. Nathanson

  DOI：10.1021/acsmedchemlett.9b00599

  日期：2020.10.8

  The epidermal growth factor receptor (EGFR) is genetically altered in nearly 60% of glioblastoma tumors; however, tyrosine kinase inhibitors (TKIs) against EGFR have failed to show efficacy for patients with these lethal brain tumors. This failure is attributed to the inability of clinically tested EGFR TKIs to cross the blood-brain barrier (BBB) and achieve adequate pharmacological levels to inhibit various oncogenic forms of EGFR that drive glioblastoma. Through SAR analysis, we developed compound 5 (JCN037) from an anilinoquinazoline scaffold by ring fusion of the 6,7-dialkoxy groups to reduce the number of rotatable bonds and polar surface area and by introduction of an orthofluorine and meta-bromine on the aniline ring for improved potency and BBB penetration. Relative to the conventional EGFR TKIs erlotinib and lapatinib, JCN037 displayed potent activity against EGFR amplified/mutant patient-derived cell cultures, significant BBB penetration (2:1 brain-to-plasma ratio), and superior efficacy in an EGFR-driven orthotopic glioblastoma xenograft model.