2-bromo-1-(4'-methoxyphenyl)-4-methylpentan-1-one | 33720-04-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-bromo-1-(4'-methoxyphenyl)-4-methylpentan-1-one
• 英文别名: 2-Bromo-1-(4-methoxyphenyl)-4-methyl-1-pentanone；2-bromo-1-(4-methoxyphenyl)-4-methylpentan-1-one
• CAS: 33720-04-6
• 化学式: C₁₃H₁₇BrO₂
• 分子量: 285.181
• InChiKey: LHNNMWLCWUEDOQ-UHFFFAOYSA-N

物化性质

• 沸点：
  350.8±17.0 °C(predicted)
• 密度：
  1.267±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-bromo-1-(4'-methoxyphenyl)-4-methylpentan-1-one 在 sodium azide 、 水 、 三苯基膦 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 2,5-bis-isobutyl-3,6-bis-(4'-methoxyphenyl)-pyrazine
  参考文献：
  名称：

  Estrogenic diazenes: heterocyclic non-steroidal estrogens of unusual structure with selectivity for estrogen receptor subtypes

  摘要：

  Estrogens regulate many biological functions, often acting in a tissue-selective manner. Their tissue-selective action is believed to involve differential estrogen action through the two estrogen receptor (ER) subtypes, ERalpha and ERbeta, as well as differential interaction of the ligand-receptor complexes with promoters and coregulator proteins. In the latter case, selectivity is based on the induction of specific conformations of the ligand-ER complex, conformations that are influenced by the structure of the ligand. Estrogen pharmaceuticals having an ideal balance of tissue-selective activity are being sought for menopausal hormone replacement, breast cancer prevention and therapy, and other actions. To expand on the structural diversity of ER ligands that might show such tissue selectivity, we have prepared a series of diazenes (pyrazines, pyrimidines, and pyridazines) substituted with two to four aryl groups and various short-chain aliphatic substituents. All of the pyrazine and pyrimidines bind to ER, some with high affinity and with a considerable degree of preferential binding to either ERalpha or ERbeta. One pyrimidine and one pyrazine have ERalpha affinity preferences as high as 23 and 9, respectively, and one pyrimidine has an ERP affinity preference of 8. The pyridazines, by contrast, are quite polar and have only very low binding affinity for the ER. In cell-based transcription assays, several of the pyrimidines and a pyrazine were found to be considerably more agonistic on ERalpha than on ERbeta. Because these triaryl diazenes have the largest volumes among the ER ligands so far investigated, their high affinity demonstrates the flexibility of the ligand binding pocket of the ERs and its tolerance for large substituents. Thus, these novel heterocyclic ligands expand the repertoire of chemical structures that bind to the estrogen receptor, and they could prove to be useful in elucidating the biological behavior of the two ER subtypes and in forming the basis for new estrogen pharmaceuticals having desirable tissue selectivity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00309-7
• 作为产物：
  描述：

  1-(4-甲氧基苯基)-4-甲基戊-1-酮 在 溴 、 溶剂黄146 作用下， 以 乙醚 为溶剂， 以93%的产率得到2-bromo-1-(4'-methoxyphenyl)-4-methylpentan-1-one
  参考文献：
  名称：

  Estrogenic diazenes: heterocyclic non-steroidal estrogens of unusual structure with selectivity for estrogen receptor subtypes

  摘要：

  Estrogens regulate many biological functions, often acting in a tissue-selective manner. Their tissue-selective action is believed to involve differential estrogen action through the two estrogen receptor (ER) subtypes, ERalpha and ERbeta, as well as differential interaction of the ligand-receptor complexes with promoters and coregulator proteins. In the latter case, selectivity is based on the induction of specific conformations of the ligand-ER complex, conformations that are influenced by the structure of the ligand. Estrogen pharmaceuticals having an ideal balance of tissue-selective activity are being sought for menopausal hormone replacement, breast cancer prevention and therapy, and other actions. To expand on the structural diversity of ER ligands that might show such tissue selectivity, we have prepared a series of diazenes (pyrazines, pyrimidines, and pyridazines) substituted with two to four aryl groups and various short-chain aliphatic substituents. All of the pyrazine and pyrimidines bind to ER, some with high affinity and with a considerable degree of preferential binding to either ERalpha or ERbeta. One pyrimidine and one pyrazine have ERalpha affinity preferences as high as 23 and 9, respectively, and one pyrimidine has an ERP affinity preference of 8. The pyridazines, by contrast, are quite polar and have only very low binding affinity for the ER. In cell-based transcription assays, several of the pyrimidines and a pyrazine were found to be considerably more agonistic on ERalpha than on ERbeta. Because these triaryl diazenes have the largest volumes among the ER ligands so far investigated, their high affinity demonstrates the flexibility of the ligand binding pocket of the ERs and its tolerance for large substituents. Thus, these novel heterocyclic ligands expand the repertoire of chemical structures that bind to the estrogen receptor, and they could prove to be useful in elucidating the biological behavior of the two ER subtypes and in forming the basis for new estrogen pharmaceuticals having desirable tissue selectivity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00309-7

文献信息

• Optimization of pyrazole-containing 1,2,4-triazolo-[3,4-b]thiadiazines, a new class of STAT3 pathway inhibitors
  作者：Matthew G. LaPorte、Zhuzhu Wang、Raffaele Colombo、Atefeh Garzan、Vsevolod A. Peshkov、Mary Liang、Paul A. Johnston、Mark E. Schurdak、Malabika Sen、Daniel P. Camarco、Yun Hua、Netanya I. Pollock、John S. Lazo、Jennifer R. Grandis、Peter Wipf、Donna M. Huryn

  DOI：10.1016/j.bmcl.2016.06.017

  日期：2016.8

  studies of a 1,2,4-triazolo-[3,4-b]thiadiazine scaffold, identified in an HTS campaign for selective STAT3 pathway inhibitors, determined that a pyrazole group and specific aryl substitution on the thiadiazine were necessary for activity. Improvements in potency and metabolic stability were accomplished by the introduction of an α-methyl group on the thiadiazine. Optimized compounds exhibited anti-proliferative

  在1,2-，3,4-三唑并[3,4- b ]噻二嗪支架上的结构-活性关系研究在针对选择性STAT3途径抑制剂的HTS运动中确定，确定吡唑基和噻二嗪上的特定芳基取代是必要的活动。通过在噻二嗪上引入α-甲基来实现效力和代谢稳定性的改善。优化的化合物表现出抗增殖活性，磷酸化的STAT3水平降低以及对STAT3目标基因的影响。这些化合物代表了针对STAT3途径的进一步药物发现努力的起点。
• [EN] EIF4E INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'EIF4E ET LEURS UTILISATIONS
  申请人：[en]PIC THERAPEUTICS, INC.

  公开号：WO2023028235A1

  公开（公告）日：2023-03-02

  The present invention provides compounds inhibiting eIF4E activity, and compositions and methods of using thereof.