N-(3-chloro-4-fluorophenyl)-3-hydroxynaphthalene-2-carboxamide | 1174069-44-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(3-chloro-4-fluorophenyl)-3-hydroxynaphthalene-2-carboxamide
• CAS: 1174069-44-3
• 化学式: C₁₇H₁₁ClFNO₂
• 分子量: 315.731
• InChiKey: GRONZNHPOIATDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-chloro-4-fluorophenyl)-3-hydroxynaphthalene-2-carboxamide 、 环氧氯丙烷 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 N-(3-chloro-4-fluorophenyl)-3-(oxiran-2-ylmethoxy)-2-naphthamide
  参考文献：
  名称：

  Vattipalli, Ramya; Shirodkar, Prabhakar Y.; Somani, Rakesh R., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2008, vol. 47, # 10, p. 1587 - 1590

  摘要：

  DOI：
• 作为产物：
  描述：

  2-羟基-3-萘甲酸 在 氯化亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 N-(3-chloro-4-fluorophenyl)-3-hydroxynaphthalene-2-carboxamide
  参考文献：
  名称：

  Structure–activity relationship studies of naphthol AS-E and its derivatives as anticancer agents by inhibiting CREB-mediated gene transcription

  摘要：

  CREB (cyclic AMP-response element binding protein) is a downstream transcription factor of a multitude of signaling pathways emanating from receptor tyrosine kinases or G-protein coupled receptors. CREB is not activated until it is phosphorylated at Ser133 and its subsequent binding to CREB-binding protein (CBP) through kinase-inducible domain (KID) in CREB and KID-interacting (KIX) domain in CBP. Tumor tissues from various organs present higher level of expression and activation of CREB. Thus CREB has been proposed as a promising cancer drug target. We previously described naphthol AS-E (1a) as a small molecule inhibitor of CREB-mediated gene transcription in living cells. Here we report the structure-activity relationship (SAR) studies of la by modifying the appendant phenyl ring. All the compounds were evaluated for in vitro inhibition of KIX-KID interaction, cellular inhibition of CREB-mediated gene transcription and inhibition of proliferation of four cancer cell lines (A549, MCF-7, MDA-MB-231 and MDA-MB-468). SAR indicated that a small and electron-withdrawing group was preferred at the para-position for KIX-KID interaction inhibition. Compound la was selected for further biological characterization and it was found that la down-regulated the expression of endogenous CREB target genes. Expression of a constitutively active CREB mutant, VP16-CREB in MCF-7 cells rendered the cells resistant to la, suggesting that CREB was critical in mediating its anticancer activity. Furthermore, la was not toxic to normal human cells. Collectively, these data support that la represents a structural template for further development into potential cancer therapeutics with a novel mechanism of action. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.056

文献信息

• US8653086B2
  申请人：——

  公开号：US8653086B2

  公开（公告）日：2014-02-18
• Structure–activity relationship studies of naphthol AS-E and its derivatives as anticancer agents by inhibiting CREB-mediated gene transcription
  作者：Bingbing X. Li、Kinrin Yamanaka、Xiangshu Xiao

  DOI：10.1016/j.bmc.2012.09.056

  日期：2012.12

  CREB (cyclic AMP-response element binding protein) is a downstream transcription factor of a multitude of signaling pathways emanating from receptor tyrosine kinases or G-protein coupled receptors. CREB is not activated until it is phosphorylated at Ser133 and its subsequent binding to CREB-binding protein (CBP) through kinase-inducible domain (KID) in CREB and KID-interacting (KIX) domain in CBP. Tumor tissues from various organs present higher level of expression and activation of CREB. Thus CREB has been proposed as a promising cancer drug target. We previously described naphthol AS-E (1a) as a small molecule inhibitor of CREB-mediated gene transcription in living cells. Here we report the structure-activity relationship (SAR) studies of la by modifying the appendant phenyl ring. All the compounds were evaluated for in vitro inhibition of KIX-KID interaction, cellular inhibition of CREB-mediated gene transcription and inhibition of proliferation of four cancer cell lines (A549, MCF-7, MDA-MB-231 and MDA-MB-468). SAR indicated that a small and electron-withdrawing group was preferred at the para-position for KIX-KID interaction inhibition. Compound la was selected for further biological characterization and it was found that la down-regulated the expression of endogenous CREB target genes. Expression of a constitutively active CREB mutant, VP16-CREB in MCF-7 cells rendered the cells resistant to la, suggesting that CREB was critical in mediating its anticancer activity. Furthermore, la was not toxic to normal human cells. Collectively, these data support that la represents a structural template for further development into potential cancer therapeutics with a novel mechanism of action. (C) 2012 Elsevier Ltd. All rights reserved.
• Vattipalli, Ramya; Shirodkar, Prabhakar Y.; Somani, Rakesh R., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2008, vol. 47, # 10, p. 1587 - 1590
  作者：Vattipalli, Ramya、Shirodkar, Prabhakar Y.、Somani, Rakesh R.、Kadam, Vilasrao J.

  DOI：——

  日期：——