1-benzo[b]thiophen-3-yl-ethanone oxime | 1131-05-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 1-benzo[b]thiophen-3-yl-ethanone oxime
• 英文别名: 1-Benzo[b]thiophen-3-yl-aethanon-oxim；3-Acetoxybenzothiophenoxim；3-Acetylbenzothiophenoxim；(NE)-N-[1-(1-benzothiophen-3-yl)ethylidene]hydroxylamine
• CAS: 1131-05-1
• 化学式: C₁₀H₉NOS
• 分子量: 191.254
• InChiKey: UAFWAHGCQKEDOA-YRNVUSSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-benzo[b]thiophen-3-yl-ethanone oxime 在 盐酸 、 吡啶硼烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 2.17h， 生成 N-hydroxy-N-(1-benzo[b]thien-3-ylethyl) urea
  参考文献：
  名称：

  Structure−Activity Relationships of N-Hydroxyurea 5-Lipoxygenase Inhibitors

  摘要：

  The discovery of second generation N-hydroxyurea 5-lipoxygenase inhibitors was accomplished through the development of a broad structure-activity relationship (SAR) study. This study identified requirements for improving potency and also extending duration by limiting metabolism. Potency could be maintained by the incorporation of heterocyclic templates substituted with selected lipophilic substituents. Duration of inhibition after oral administration was optimized by identification of structural features in the proximity of the N-hydroxyurea which correlated to low in vitro glucuronidation rates. Furthermore, the rate of in vitro glucuronidation was shown to be stereoselective for certain analogs. (R)-N-[3-[5-(4-Fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]-N-hy- droxyurea (17c) was identified and selected for clinical development.

  DOI：

  10.1021/jm9700474
• 作为产物：
  描述：

  3-乙酰硫茚 在 吡啶 、 盐酸羟胺 作用下， 生成 1-benzo[b]thiophen-3-yl-ethanone oxime
  参考文献：
  名称：

  发现二氧代-苯并 [b] 噻吩衍生物作为治疗乳腺癌的有效 YAP-TEAD 相互作用抑制剂

  摘要：

  转录增强因子 (TEA) 结构域（TEAD；一种转录因子）与其共激活因子 Yes 相关蛋白 (YAP)/具有 PDZ 结合基序的转录共激活因子 (TAZ) 之间的蛋白质-蛋白质相互作用的破坏是一个潜在的针对各种类型的实体瘤的治疗策略。基于命中化合物8和9a，设计了与二氧代苯并[ d ]异噻唑（9b-n）和肟酯（10a-s）或酰胺衍生物（11a-r）与二氧代苯并[ b ]噻吩的腙衍生物，并合成为新型 TEAD-YAP 相互作用抑制剂。酰胺衍生物11q在抑制 TEAD-YAP 报告基因表达活性 (IC 50  = 12.7 μM)、内源性靶基因（例如 CTGF 和 CYR61）表达、乳腺癌细胞生长 (GI 50  = 3.2 μM) 和不依赖锚定的生长方面表现出更高的效力软琼脂。分子对接分析表明，与结合到界面 3 的化合物相比，新合成的与 TEAD 界面 2 结合的化合物具有较低的对接分数；此外，预计它们会与

  DOI：

  10.1016/j.bioorg.2022.106274

文献信息

• 3-SUBSTITUTED THIANAPHTHENES
  作者：CORWIN HANSCH、H. G. LINDWALL

  DOI：10.1021/jo01181a001

  日期：1945.9
• US4740230A
  申请人：——

  公开号：US4740230A

  公开（公告）日：1988-04-26
• Structure−Activity Relationships of <i>N</i>-Hydroxyurea 5-Lipoxygenase Inhibitors
  作者：Andrew O. Stewart、Pramila A. Bhatia、Jonathan G. Martin、James B. Summers、Karen E. Rodriques、Michael B. Martin、James H. Holms、Jimmie L. Moore、Richard A. Craig、Teodozyj Kolasa、James D. Ratajczyk、Hormoz Mazdiyasni、Francis A. J. Kerdesky、Shari L. DeNinno、Robert G. Maki、Jennifer B. Bouska、Patrick R. Young、Carmine Lanni、Randy L. Bell、George W. Carter、Clint D. W. Brooks

  DOI：10.1021/jm9700474

  日期：1997.6.1

  The discovery of second generation N-hydroxyurea 5-lipoxygenase inhibitors was accomplished through the development of a broad structure-activity relationship (SAR) study. This study identified requirements for improving potency and also extending duration by limiting metabolism. Potency could be maintained by the incorporation of heterocyclic templates substituted with selected lipophilic substituents. Duration of inhibition after oral administration was optimized by identification of structural features in the proximity of the N-hydroxyurea which correlated to low in vitro glucuronidation rates. Furthermore, the rate of in vitro glucuronidation was shown to be stereoselective for certain analogs. (R)-N-[3-[5-(4-Fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]-N-hy- droxyurea (17c) was identified and selected for clinical development.
• Discovery of dioxo-benzo[b]thiophene derivatives as potent YAP-TEAD interaction inhibitors for treating breast cancer
  作者：Youngchai Son、Jaeyeal Kim、Yongchan Kim、Sung-Gil Chi、Tackhoon Kim、Jinha Yu

  DOI：10.1016/j.bioorg.2022.106274

  日期：2023.2

  hydrazone derivatives with dioxo-benzo[d]isothiazole (9b–n) and oxime ester (10a-s) or amide derivatives (11a-r) with dioxo-benzo[b]thiophene were designed and synthesized as novel TEAD-YAP interaction inhibitors. Amide derivative 11q exhibited a higher potency in inhibiting TEAD-YAP reporter expression activity (IC50 = 12.7 μM), endogenous target gene (e.g., CTGF and CYR61) expression, breast cancer cell

  转录增强因子 (TEA) 结构域（TEAD；一种转录因子）与其共激活因子 Yes 相关蛋白 (YAP)/具有 PDZ 结合基序的转录共激活因子 (TAZ) 之间的蛋白质-蛋白质相互作用的破坏是一个潜在的针对各种类型的实体瘤的治疗策略。基于命中化合物8和9a，设计了与二氧代苯并[ d ]异噻唑（9b-n）和肟酯（10a-s）或酰胺衍生物（11a-r）与二氧代苯并[ b ]噻吩的腙衍生物，并合成为新型 TEAD-YAP 相互作用抑制剂。酰胺衍生物11q在抑制 TEAD-YAP 报告基因表达活性 (IC 50  = 12.7 μM)、内源性靶基因（例如 CTGF 和 CYR61）表达、乳腺癌细胞生长 (GI 50  = 3.2 μM) 和不依赖锚定的生长方面表现出更高的效力软琼脂。分子对接分析表明，与结合到界面 3 的化合物相比，新合成的与 TEAD 界面 2 结合的化合物具有较低的对接分数；此外，预计它们会与