1-(2,3-Dichloro-4-methoxy-phenyl)-2-methylene-butan-1-one | 59043-82-2

• 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: 1-(2,3-Dichloro-4-methoxy-phenyl)-2-methylene-butan-1-one
• 英文别名: 1-(2,3-Dichloro-4-methoxyphenyl)-2-methylidenebutan-1-one
• CAS: 59043-82-2
• 化学式: C₁₂H₁₂Cl₂O₂
• 分子量: 259.132
• InChiKey: ZXIMVQPKWOKVHA-UHFFFAOYSA-N

物化性质

• 熔点：
  46-48 °C
• 沸点：
  370.3±42.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  1-(2,3-Dichloro-4-methoxy-phenyl)-2-methylene-butan-1-one 在 sodium hydroxide 、 硫酸 、 吡啶盐酸盐 、 苄基三甲基氢氧化铵 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 34.0h， 生成 5,6-dichloro-9a-ethyl-1,2,9,9a-tetrahydro-7-hydroxy-3H-fluoren-3-one
  参考文献：
  名称：

  Agents for the treatment of brain edema. 2. [(2,3,9,9a-Tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]alkanoic acids and some of their analogs

  摘要：

  Our initial paper discussed brain edema resulting from traumatic head injury and the need for specific and effective agents to treat the disorder and disclosed a novel approach for the discovery of a drug of this kind. The current study describes the synthesis of a series of [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]alk anoic acids and their analogues. These compounds were evaluated in an in vitro cerebrocortical tissue slice assay for their relative potencies in inhibiting K+ + HCO3- induced swelling. Structural modification at a number of sites in the "lead" compound revealed that significant biological activity was inherent only within a very narrow range of structural types. The observation that nearly all the biological activity resided in one of the two enantiomers demonstrated the marked stereospecificity of the most active compounds. One of the most potent compounds, (R)-(+)-[(5,6-dichloro-2,3,9,9a-tetrahydro-3-oxo-9a-propyl-1H-fluoren -7-yl) oxy]acetic acid ((+)-5c), exhibited a dose-response relationship in the in vivo acceleration/deceleration brain edema assay, and the data from the two highest doses were statistically significant. Electron microscopic examination demonstrated that the perivascular astroglial swelling that arises from this procedure is abolished in the animals treated with (+)-5c. This compound is currently being evaluated for its clinical efficacy and safety in the treatment of traumatic head injury.

  DOI：

  10.1021/jm00155a038
• 作为产物：
  描述：

  2,3-二氯茴香醚 在 三氯化铝 、 乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 1-(2,3-Dichloro-4-methoxy-phenyl)-2-methylene-butan-1-one
  参考文献：
  名称：

  Agents for the treatment of brain edema. 2. [(2,3,9,9a-Tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]alkanoic acids and some of their analogs

  摘要：

  Our initial paper discussed brain edema resulting from traumatic head injury and the need for specific and effective agents to treat the disorder and disclosed a novel approach for the discovery of a drug of this kind. The current study describes the synthesis of a series of [(2,3,9,9a-tetrahydro-3-oxo-9a-substituted-1H-fluoren-7-yl)oxy]alk anoic acids and their analogues. These compounds were evaluated in an in vitro cerebrocortical tissue slice assay for their relative potencies in inhibiting K+ + HCO3- induced swelling. Structural modification at a number of sites in the "lead" compound revealed that significant biological activity was inherent only within a very narrow range of structural types. The observation that nearly all the biological activity resided in one of the two enantiomers demonstrated the marked stereospecificity of the most active compounds. One of the most potent compounds, (R)-(+)-[(5,6-dichloro-2,3,9,9a-tetrahydro-3-oxo-9a-propyl-1H-fluoren -7-yl) oxy]acetic acid ((+)-5c), exhibited a dose-response relationship in the in vivo acceleration/deceleration brain edema assay, and the data from the two highest doses were statistically significant. Electron microscopic examination demonstrated that the perivascular astroglial swelling that arises from this procedure is abolished in the animals treated with (+)-5c. This compound is currently being evaluated for its clinical efficacy and safety in the treatment of traumatic head injury.

  DOI：

  10.1021/jm00155a038

文献信息

• Compound I and compound II as well as preparation methods therefor and application thereof
  申请人：SHENZHEN UNIVERSITY

  公开号：US10711005B2

  公开（公告）日：2020-07-14

  Compound I and a compound II as well as preparation methods therefor and use thereof are disclosed. A newly synthesized compound of formula I is capable of stimulating congenital immunity and cellular immunity for tumor resistance while greatly improving the antitumor effect of ethacrynic acid (EA), and thus an integrated synergistic anti-tumor dual-immunity drug design is explored. The immune response mechanism for resisting melanoma of the compound as shown in the formula I is demonstrated. A compound that is as shown in a formula II and is prepared from the compound of formula I and ROR1 by means of covalency markedly slows down the growth of subcutaneously transplanted mammary cancer tumor, such that the immune response mechanism, for treating the mammary cancer, of the compound as shown in the formula II is demonstrated.

  本研究公开了化合物 I 和化合物 II 及其制备方法和用途。一种新合成的式 I 化合物能够刺激先天免疫和细胞免疫以抵抗肿瘤，同时大大提高了乙酰丙酸（EA）的抗肿瘤效果，从而探索了一种综合协同的抗肿瘤双重免疫药物设计。如式 I 所示的化合物抵抗黑色素瘤的免疫应答机制得到了证实。由式 I 化合物和 ROR1 通过共价作用制备的如式 II 所示的化合物明显减缓了皮下移植的乳腺癌肿瘤的生长，从而证明了如式 II 所示的化合物治疗乳腺癌的免疫应答机制。
• Extended release microparticles and suspensions thereof for medical therapy
  申请人：Graybug Vision, Inc.

  公开号：US11160870B2

  公开（公告）日：2021-11-02

  An improved microparticle or lyophilized or otherwise reconstitutable microparticle composition thereof for medical therapy, including ocular therapy.

  一种用于医疗（包括眼科治疗）的改良微粒或冻干或可重组微粒组合物。
• CRAGOE E. J.;WOLTERSDORF O. W.;GOULD N. P.;PIETRUSZKIEWICZ A. M.;ZIEGLER +, J. MED. CHEM., 1986, 29, N 5, 825-841
  作者：CRAGOE E. J.、WOLTERSDORF O. W.、GOULD N. P.、PIETRUSZKIEWICZ A. M.、ZIEGLER +

  DOI：——

  日期：——
• WOLTERSDORF O. W. JR.; SOLMS S. J. DE; SCHULTZ E. M.; CRAGOE E. J. JR., J. MED. CHEM. <JMCM-AR>, 1977, 20, NO 11, 1400-1408
  作者：WOLTERSDORF O. W. JR.、 SOLMS S. J. DE、 SCHULTZ E. M.、 CRAGOE E. J. JR.

  DOI：——

  日期：——
• AMIDE DERIVATIVES OF ETHACRYNIC ACID
  申请人：Carson Dennis A.

  公开号：US20110306671A1

  公开（公告）日：2011-12-15

  The invention provides ethacrynic acid derivatives useful to prevent, inhibit or treat a variety of disorders or diseases including cancer and inflammatory disorders.