2-(bromomethyl)-1,3-dichloro-4-methoxybenzene | 886615-66-3

• 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: 2-(bromomethyl)-1,3-dichloro-4-methoxybenzene
• 英文别名: 2-Bromomethyl-1,3-dichloro-4-methoxy-benzene
• CAS: 886615-66-3
• 化学式: C₈H₇BrCl₂O
• 分子量: 269.953
• InChiKey: SFPDZTWZALNDEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(bromomethyl)-1,3-dichloro-4-methoxybenzene 在 2,3-二氯-5,6-二氰基-1,4-苯醌 、 tin(ll) chloride 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 环己烷 、 甲苯 、 苯 为溶剂， 反应 93.25h， 生成 4-(2,6-dichloro-3-methoxyphenyl)-9-methoxypyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione
  参考文献：
  名称：

  4-Phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-dione Inhibitors of the Checkpoint Kinase Wee1. Structure−Activity Relationships for Chromophore Modification and Phenyl Ring Substitution

  摘要：

  High-throughput screening has identified a novel class of inhibitors of the checkpoint kinase Wee1, which have potential for use in cancer chemotherapy. These inhibitors are based on a 4-phenylpyrrolo[3,4-c]carbazole- 1,3(2H,6H)-dione template and have been shown by X-ray crystallography to bind at the ATP site of the enzyme. An extensive study of the effects of substitution around this template has been carried out, which has identified substituents which lead to improvements in potency and selectivity for Wee1. While retention of the maleimide ring and pendant 4-phenyl group is necessary for potency, replacement of the carbazole nitrogen by oxygen is well tolerated and results in improved Wee1 selectivity against the related checkpoint kinase Chk1. Wee1 potency and selectivity are also enhanced by the incorporation of lipophilic functionality at the 2'-position of the 4-phenyl ring, and Wee1 selectivity against Chk1 is favored by C3-C5 alkyl substitution of the carbazole nitrogen. These studies provide a basis for the design of active analogues of the pyrrolocarbazole lead with improved physical properties.

  DOI：

  10.1021/jm0512591
• 作为产物：
  描述：

  (2,6-dichloro-3-methoxyphenyl)methanol 在 三溴化磷 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 以57%的产率得到2-(bromomethyl)-1,3-dichloro-4-methoxybenzene
  参考文献：
  名称：

  WO2006/49952

  摘要：

  公开号：

文献信息

• 2-Aminopyrimidine Derivatives as New Selective Fibroblast Growth Factor Receptor 4 (FGFR4) Inhibitors
  作者：Cheng Mo、Zhang Zhang、Christopher P. Guise、Xueqiang Li、Jinfeng Luo、Zhengchao Tu、Yong Xu、Adam V. Patterson、Jeff B. Smaill、Xiaomei Ren、Xiaoyun Lu、Ke Ding

  DOI：10.1021/acsmedchemlett.7b00091

  日期：2017.5.11

  A series of 2-aminopyrimidine derivatives were designed and synthesized as highly selective FGFR4 inhibitors. One of the most promising compounds 2n tightly bound FGFR4 with a Kd value of 3.3 nM and potently inhibited its enzymatic activity with an IC50 value of 2.6 nM, but completely spared FGFR1/2/3. The compound selectively suppressed proliferation of breast cancer cells harboring dysregulated FGFR4

  设计并合成了一系列2-氨基嘧啶衍生物，作为高选择性FGFR4抑制剂。最有希望的化合物2n紧密结合FGFR4，其Kd值为3.3 nM，并以2.6 nM的IC50值有效抑制其酶促活性，但完全避免了FGFR1 / 2/3。该化合物选择性抑制带有FGFR4信号传导失调的乳腺癌细胞的增殖，IC50值为0.38μM。此外，2n在针对468个激酶的全基因组筛选中显示出非凡的靶标特异性，在1.0μM时S（35）和S（10）的选择性得分分别为0.01和0.007。
• Cycloalkyl Lactam Derivatives as Inhibitors of 11-Beta-Hydroxysteroid Dehydrogenase 1
  申请人：Aicher Thomas Daniel

  公开号：US20080275043A1

  公开（公告）日：2008-11-06

  The present invention discloses compounds of Formula I: (I) having 11beta-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as the use of the Fomula I and compositions as medicaments to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, Syndrome X, and other conditions associated with hyperglycemia.

  本发明公开了具有11beta-HSD type 1拮抗活性的化合物的公式I：（I），以及制备这种化合物的方法。在另一实施例中，本发明公开了包含公式I化合物的制药组合物，以及将公式I和组合物用作药物治疗糖尿病，高血糖，肥胖症，高血压，高脂血症，综合征X和与高血糖有关的其他疾病的用途。
• CYCLOALKYL LACTAM DERIVATIVES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE 1
  申请人：AICHER Thomas Daniel

  公开号：US20100184764A1

  公开（公告）日：2010-07-22

  The present invention discloses compounds of Formula I: (I) having 11beta-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as the use of the Formula I and compositions as medicaments to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, Syndrome X, and other conditions associated with hyperglycemia.

  本发明揭示了具有11beta-HSD type 1拮抗活性的I式化合物：（I），以及制备这种化合物的方法。在另一种实施方式中，本发明揭示了包括I式化合物的制药组合物，以及将I式和组合物用作药物治疗糖尿病，高血糖，肥胖症，高血压，高脂血症，X综合症和其他与高血糖有关的疾病的用途。
• Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1
  申请人：Eli Lilly and Company

  公开号：US07713979B2

  公开（公告）日：2010-05-11

  The present invention discloses compounds of Formula I: (I) having 11beta-HSD type 1 antagonist activity, as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I, as well as the use of the Formula I and compositions as medicaments to treat diabetes, hyperglycemia, obesity, hypertension, hyperlipidemia, Syndrome X, and other conditions associated with hyperglycemia.

  本发明公开了具有11beta-HSD类型1拮抗活性的I式化合物(I)，以及制备这些化合物的方法。在另一实施例中，本发明公开了包含I式化合物的药物组合物，以及将I式化合物和组合物用作药物治疗糖尿病、高血糖、肥胖症、高血压、高脂血症、X综合症以及与高血糖相关的其他病症的用途。
• US7713979B2
  申请人：——

  公开号：US7713979B2

  公开（公告）日：2010-05-11