SDZ LAP 977 | 150779-71-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: SDZ LAP 977
• 英文别名: 5-[2-(2,5-dimethoxyphenyl)ethyl]-2-hydroxybenzoic acid methyl ester；Sdz-lap-977；methyl 5-[2-(2,5-dimethoxyphenyl)ethyl]-2-hydroxybenzoate
• CAS: 150779-71-8
• 化学式: C₁₈H₂₀O₅
• 分子量: 316.354
• InChiKey: GZOFTOHENYHNMS-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性

SDZ 281-977 是 EGF 受体酪氨酸激酶抑制剂 Lavendustin A 的衍生物。

体外研究

SDZ 281-977 对携带人肿瘤细胞系 A431（外阴癌细胞）、MIA PaCa-2（胰腺癌细胞）和 MDA-MB-231（乳腺癌细胞）的裸鼠的人类肿瘤模型进行了抗癌效果的研究。这些细胞系因其对 SDZ 281-977 的敏感性被选择使用。A431、MIA PaCa-2 和 MDA-MB-231 细胞的生长抑制 IC50 值分别为 0.21 μM、0.29 μM 和 0.43 μM。

体内研究

携带 A431 人外阴癌裸鼠接受 SDZ 281-977（1-10 mg/kg）的静脉注射，连续 4 周。这种治疗表现出剂量依赖性的肿瘤生长抑制作用。口服给药 SDZ 281-977（30 mg/kg），经过 3 周治疗后，可使 A431 肿瘤的增生减少 54%。采用上述给药方案，治疗过程耐受性良好，未见明显体重变化。

反应信息

• 作为反应物：
  描述：

  SDZ LAP 977 在 sodium hydroxide 、 三溴化硼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.17h， 生成 5-[2-(2,5-二羟基苯基)乙基]-2-羟基苯甲酸
  参考文献：
  名称：

  Novel Antiproliferative Agents Derived from Lavendustin A

  摘要：

  The active partial structure of the potent tyrosine kinase inhibitor lavendustin A was derivatized in the search for novel agents against cellular proliferation. The antiproliferative potential of the new derivatives was determined using the human keratinocyte cell line HaCaT as the primary test system. Whereas the lavendustin A partial structure is ineffective in inhibiting cell proliferation, esterification of its carboxylic acid function leads to measurable antiproliferative activity. Additional O-methylation of the 2,5-dihydroxyphenyl moiety yields activity in the micromolar range. Further substantial increases in activity are achieved by replacing the nitrogen with oxygen and carbon within the 2,5-dimethoxyphenyl series (but not within the 2,5-dihydroxyphenyl analogs) leading to 5-[2-(2,5-dimethoxyphenyl)ethyl]-2-hydroxybenzoic acid methyl ester (13) as the most potent analog identified to date. These increases in antiproliferative activity are paralleled, however, by the disappearance of activity against the epidermal growth factor receptor-associated tyrosine kinase, suggesting another mechanism of action.

  DOI：

  10.1021/jm00050a005
• 作为产物：
  描述：

  (2,5-dimethoxybenzyl)triphenylphosphonium bromide 在 palladium on activated charcoal 正丁基锂 、 氢气 、 二异丙胺 作用下， 以 乙酸乙酯 为溶剂， -70.0~25.0 ℃ 、98.06 kPa 条件下， 反应 34.0h， 生成 SDZ LAP 977
  参考文献：
  名称：

  Novel Antiproliferative Agents Derived from Lavendustin A

  摘要：

  The active partial structure of the potent tyrosine kinase inhibitor lavendustin A was derivatized in the search for novel agents against cellular proliferation. The antiproliferative potential of the new derivatives was determined using the human keratinocyte cell line HaCaT as the primary test system. Whereas the lavendustin A partial structure is ineffective in inhibiting cell proliferation, esterification of its carboxylic acid function leads to measurable antiproliferative activity. Additional O-methylation of the 2,5-dihydroxyphenyl moiety yields activity in the micromolar range. Further substantial increases in activity are achieved by replacing the nitrogen with oxygen and carbon within the 2,5-dimethoxyphenyl series (but not within the 2,5-dihydroxyphenyl analogs) leading to 5-[2-(2,5-dimethoxyphenyl)ethyl]-2-hydroxybenzoic acid methyl ester (13) as the most potent analog identified to date. These increases in antiproliferative activity are paralleled, however, by the disappearance of activity against the epidermal growth factor receptor-associated tyrosine kinase, suggesting another mechanism of action.

  DOI：

  10.1021/jm00050a005

文献信息

• Bis(phenyl)ethane derivatives
  申请人：Sandoz Ltd.

  公开号：US05488135A1

  公开（公告）日：1996-01-30

  The invention concerns the compounds of formula I ##STR1## wherein the substituents have various significances, in free form and, where such forms exist, in salt form. The compounds have potent antihyperproliferative/antiinflammatory and anticancer activity.

  本发明涉及公式I的化合物 ##STR1## 其中取代基具有各种意义，包括自由形式和盐形式（如果存在这些形式）。这些化合物具有强效的抗高增殖/抗炎和抗癌活性。
• Bis (phenyl)ethane derivatives
  申请人：SANDOZ LTD.

  公开号：EP0539326B1

  公开（公告）日：1996-04-10
• JPH05213828A
  申请人：——

  公开号：JPH05213828A

  公开（公告）日：1993-08-24
• US5488135A
  申请人：——

  公开号：US5488135A

  公开（公告）日：1996-01-30
• Novel Antiproliferative Agents Derived from Lavendustin A
  作者：Peter Nussbaumer、Anthony P. Winiski、Salvatore Cammisuli、Peter Hiestand、Gisbert Weckbecker、Anton Stuetz

  DOI：10.1021/jm00050a005

  日期：1994.11

  The active partial structure of the potent tyrosine kinase inhibitor lavendustin A was derivatized in the search for novel agents against cellular proliferation. The antiproliferative potential of the new derivatives was determined using the human keratinocyte cell line HaCaT as the primary test system. Whereas the lavendustin A partial structure is ineffective in inhibiting cell proliferation, esterification of its carboxylic acid function leads to measurable antiproliferative activity. Additional O-methylation of the 2,5-dihydroxyphenyl moiety yields activity in the micromolar range. Further substantial increases in activity are achieved by replacing the nitrogen with oxygen and carbon within the 2,5-dimethoxyphenyl series (but not within the 2,5-dihydroxyphenyl analogs) leading to 5-[2-(2,5-dimethoxyphenyl)ethyl]-2-hydroxybenzoic acid methyl ester (13) as the most potent analog identified to date. These increases in antiproliferative activity are paralleled, however, by the disappearance of activity against the epidermal growth factor receptor-associated tyrosine kinase, suggesting another mechanism of action.