ethyl 5-bromo-6-bromomethyl-2-methoxybenzoate | 133379-05-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 5-bromo-6-bromomethyl-2-methoxybenzoate
• 英文别名: ethyl 3-bromo-2-(bromomethyl)-6-methoxybenzoate
• CAS: 133379-05-2
• 化学式: C₁₁H₁₂Br₂O₃
• 分子量: 352.022
• InChiKey: ADIIVKVDUDCWPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 5-bromo-6-bromomethyl-2-methoxybenzoate 在 氨 、 氢溴酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 64.0h， 生成 4-溴-7-羟基异吲哚啉-1-酮
  参考文献：
  名称：

  Design and Synthesis of Pyrrolo[3,2-d]pyrimidine Human Epidermal Growth Factor Receptor 2 (HER2)/Epidermal Growth Factor Receptor (EGFR) Dual Inhibitors: Exploration of Novel Back-Pocket Binders

  摘要：

  To develop novel human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) kinase inhibitors, we explored pyrrolo[3,2-d]pyrimidine derivatives bearing bicyclic fused rings designed to fit the back pocket of the HER2/EGFR proteins. Among them, the 1,2-benzisothiazole (42m) ring was selected as a suitable back pocket binder because of its potent HER2/EGFR binding and cell growth inhibitory (GI) activities and pseudoirreversibility (PI) profile as well as good bioavailability (BA). Ultimately, we arrived at our preclinical candidate 51m by optimization of the N-5 side chain to improve CYP inhibition and metabolic stability profiles without a loss of potency (HER2/EGFR inhibitory activity, IC50, 0.98/2.5 nM; and GI activity BT-474 cells, GI(50), 2.0 nM). Reflecting the strong in vitro activities, 51m exhibited potent tumor regressive efficacy against both HER2- and EGFR-overexpressing tumor (4-1ST and CAL27) xenograft models in mice at oral doses of 50 mg/kg and 100 mg/kg.

  DOI：

  10.1021/jm300185p
• 作为产物：
  描述：

  2-甲氧基-6-甲基苯甲酸乙酯 在 溴 作用下， 以 四氯化碳 为溶剂， 反应 17.0h， 以54%的产率得到ethyl 5-bromo-6-bromomethyl-2-methoxybenzoate
  参考文献：
  名称：

  Islam, Md. Rabiul; Joule, John A., Journal of Chemical Research, Miniprint, 1991, # 2, p. 367 - 378

  摘要：

  DOI：

文献信息

• [EN] METHODS AND COMPOUNDS FOR RESTORING MUTANT p53 FUNCTION<br/>[FR] MÉTHODES ET COMPOSÉS DESTINÉS À LA RESTAURATION D'UNE FONCTION DE MUTANTS DE P53
  申请人：PMV PHARMACEUTICALS INC

  公开号：WO2021262684A1

  公开（公告）日：2021-12-30

  Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods that restore DNA binding affinity of p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

  癌基因和肿瘤抑制基因的突变促成了癌症的发展和进展。本公开披露描述了一种恢复p53突变体DNA结合亲和力的化合物和方法。本公开披露的化合物可以结合突变型p53，并恢复p53突变体结合DNA并激活参与肿瘤抑制的下游效应子的能力。披露的化合物可用于减少含有p53突变的癌症的进展。
• NITROGEN-CONTAINING HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2921480B1

  公开（公告）日：2017-10-11
• Islam, Md. Rabiul; Joule, John A., Journal of Chemical Research, Miniprint, 1991, # 2, p. 367 - 378
  作者：Islam, Md. Rabiul、Joule, John A.

  DOI：——

  日期：——
• ISLAM, MD. RABIUL;JOULE, JOHN A.
  作者：ISLAM, MD. RABIUL、JOULE, JOHN A.

  DOI：——

  日期：——
• US9777005B2
  申请人：——

  公开号：US9777005B2

  公开（公告）日：2017-10-03