3-Methoxymethoxy-2-naphtoesaeure | 34610-70-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-Methoxymethoxy-2-naphtoesaeure
• 英文别名: 3-(Methoxymethoxy)-2-naphthalenecarboxylic acid；3-(methoxymethoxy)naphthalene-2-carboxylic acid
• CAS: 34610-70-3
• 化学式: C₁₃H₁₂O₄
• mdl: MFCD20927724
• 分子量: 232.236
• InChiKey: QEDARVCBGGBHDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.153
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氨基吡啶 、 3-Methoxymethoxy-2-naphtoesaeure 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 生成 C₁₈H₁₆N₂O₃
  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
• 作为产物：
  描述：

  3-Methoxymethoxy-2-naphtoesaeuremethylester 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 3-Methoxymethoxy-2-naphtoesaeure
  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

• [EN] NAPHTHAMIDES AS ANTICANCER AGENTS<br/>[FR] NAPHTHAMIDES EN TANT QU'AGENTS ANTI-CANCÉREUX
  申请人：UNIV OREGON HEALTH & SCIENCE

  公开号：WO2010048302A1

  公开（公告）日：2010-04-29

  A compound (particularly useful for inhibiting cancer) according to formula (I): or a pharmaceutically acceptable salt thereof, wherein: x is 0 or 1; R1-R6 are each independently H, -CN, -NO2, -NO, -OH, halogen, hydroxyalkyl, carboxyl, substituted carboxyl, aminocarbonyl, alkoxy, carbonyl or substituted carbonyl; R7 is H, alkyl, alkyl amino, aminoacyl, hydroxyacyl, heteroaryl, heterocycloalkyi, alkyl heteroaryl or alkyl heterocycloalkyl; R8 is H or alkyl; A is O or N; and Ar is an aryl, substituted aryl, heteroaryl, or substituted heleroaryl, provided that if R7 is H then Ar is aryl substituted with alkyl amino.

  一种化合物（特别适用于抑制癌症），其化学式为（I）或其药学上可接受的盐，其中：x为0或1；R1-R6各自独立地为H，-CN，-NO2，-NO，-OH，卤素，羟基烷基，羧基，取代羧基，氨基甲酰基，烷氧基，羰基或取代羰基；R7为H，烷基，烷基氨基，氨基酰基，羟基酰基，杂环芳基，杂环环烷基，烷基杂环芳基或烷基杂环环烷基；R8为H或烷基；A为O或N；Ar为芳基，取代芳基，杂环芳基或取代杂环芳基，但如果R7为H，则Ar为取代烷基氨基的芳基。
• Naphthalene carboxamides as inhibitors of human cytomegalovirus DNA polymerase
  作者：Valerie A Vaillancourt、Michele M Cudahy、Sandra A Staley、Roger J Brideau、Steven J Conrad、Mary L Knechtel、Nancee L Oien、Janet L Wieber、Yoshihiko Yagi、Michael W Wathen

  DOI：10.1016/s0960-894x(00)00402-9

  日期：2000.9

  ortho-Hydroxynaphthalene carboxamides have been identified as inhibitors of HCMV DNA polymerase. SAR investigations have demonstrated that both the amide and hydroxy functionalities are required for activity. Substitution on the naphthalene ring has led to inhibitors with submicromolar IC(50)s against HCMV polymerase. These compounds have been found to be >100-fold selective for inhibition of HCMV polymerase versus human alpha polymerase and display antiviral activity in a cell-based plaque reduction assay. (C) 2000 Elsevier Science Ltd. All rights reserved.
• US5583222A
  申请人：——

  公开号：US5583222A

  公开（公告）日：1996-12-10
• US5750706A
  申请人：——

  公开号：US5750706A

  公开（公告）日：1998-05-12
• US5914406A
  申请人：——

  公开号：US5914406A

  公开（公告）日：1999-06-22