acetic acid 2-(6,6-dimethoxy-3-oxocyclohexa-1,4-dienylcarbamoyl)phenyl ester | 287194-31-4

• 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: acetic acid 2-(6,6-dimethoxy-3-oxocyclohexa-1,4-dienylcarbamoyl)phenyl ester
• 英文别名: Acetic acid [2-[[(6,6-dimethoxy-3-oxo-1-cyclohexa-1,4-dienyl)amino]-oxomethyl]phenyl] ester；[2-[(6,6-dimethoxy-3-oxocyclohexa-1,4-dien-1-yl)carbamoyl]phenyl] acetate
• CAS: 287194-31-4
• 化学式: C₁₇H₁₇NO₆
• 分子量: 331.325
• InChiKey: NYHYQDXXVQAQGX-UHFFFAOYSA-N

物化性质

• 熔点：
  150-152 °C
• 沸点：
  562.7±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  acetic acid 2-(6,6-dimethoxy-3-oxocyclohexa-1,4-dienylcarbamoyl)phenyl ester 在 sodium hydroxide 、 氢氟酸 、 双氧水 、 三乙酰氧基硼氢化钠 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 5.67h， 生成 (-)-2-hydroxy-N-(2-hydroxy-5-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl)benzamide
  参考文献：
  名称：

  Synthesis of NF-κB activation inhibitors derived from epoxyquinomicin C

  摘要：

  In order to develop new inhibitors of NF-kappa B activation, we designed and synthesized dehydroxymethyl derivatives of epoxyquinomicin C, namely, DHM2EQ and its regioisomer DHM3EQ. These derivatives were synthesized from 2,5-dimethoxyaniline in 5 steps. Since DHM2EQ was more active and less toxic than DHM3EQ, its stereochemical configuration was determined by X-ray crystallographic analysis. Each enantiomer of the protected DHM2EQ was separated by a chiral column and deprotected. DHM2EQ inhibited TNF-alpha-induced activation of NF-kappa B in human T cell leukemia cells, and also inhibited collagen-induced arthritis in a rheumatoid model in mice. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00114-1
• 作为产物：
  描述：

  在 盐酸 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 以8.03 g的产率得到acetic acid 2-(6,6-dimethoxy-3-oxocyclohexa-1,4-dienylcarbamoyl)phenyl ester
  参考文献：
  名称：

  Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor

  摘要：

  NF-kappaB is a transcription factor that induces inflammatory cytokines and anti-apoptotic proteins. We have designed a new NF-kappaB inhibitor based on the structure of the antibiotic epoxyquinomicin C. The designed compound, dehydroxymethylepoxyquinomicin (DHMEQ) was synthesized as a racemic form from 2,5-dimethoxyaniline through 5 steps. Application of racemic DHMEQ onto the chiral column (Chiralpak AD) directly gave enantiomeric DHMEQ after purification. (-)-DHMEQ was more potent than its enantiomer. (-)-DHMEQ was found to inhibit NF-kappaB activity and macrophage differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human monocyte THP-1 cells. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2004.01.103

文献信息

• Synthesis and Evaluation of a Cyclopropane Derivative of DHMEQ
  作者：Eiko Yasui、Kan Takayama、Takahiro Nakago、Nobuyuki Takeda、Yasutada Imamura、Shinji Nagumo

  DOI：10.1248/cpb.c13-00914

  日期：——

  We have synthesized an analog 4 containing a cyclopropanated quinol skeleton and examined its ability to inhibit NF-κB. Surprisingly, 4 showed no remarkable NF-κB inhibitory activity as determined through expression of cyclooxygenase-2 (COX-2) in an RAW264.7 macrophage cell line.

  众所周知，脱羟甲基环氧喹诺霉素（DHMEQ，1）可抑制核因子-κB（NF-κB），后者与免疫，炎症和凋亡过程密切相关，是一种可诱导的转录因子。抑制作用似乎是环氧化物1与p65的Cys（38）开环的结果。我们合成了含有环丙烷基喹诺酮骨架的类似物4，并研究了其抑制NF-κB的能力。出乎意料的是，通过在RAW264.7巨噬细胞系中表达环氧合酶-2（COX-2）来确定，4没有显示出明显的NF-κB抑制活性。
• SALICYLAMIDE DERIVATIVES
  申请人：MERCIAN CORPORATION

  公开号：EP1219596A1

  公开（公告）日：2002-07-03

  Salicylamide derivatives represented by formulae (1a) and (1b); intermediates in the production thereof; a process for producing the same; and drugs containing the same as the active ingredient. The salicylamide derivatives represented by formulae (1a) and (1b) are useful as anti-inflammatory agents and immunosuppressive agents which exert an effect of inhibiting the activation of NF-κB with little side effects.

  由式(1a)和(1b)代表的水杨酰胺衍生物；生产这些衍生物的中间体；生产这些衍生物的工艺；以及含有这些衍生物作为活性成分的药物。由式（1a）和（1b）代表的水杨酰胺衍生物可用作抗炎剂和免疫抑制剂，它们具有抑制 NF-κB 活化的作用，且副作用小。
• US6566394B1
  申请人：——

  公开号：US6566394B1

  公开（公告）日：2003-05-20
• Synthesis of NF-κB activation inhibitors derived from epoxyquinomicin C
  作者：Naoki Matsumoto、Akiko Ariga、Sakino To-e、Hikaru Nakamura、Naoki Agata、Shin-ichi Hirano、Jun-ichiro Inoue、Kazuo Umezawa

  DOI：10.1016/s0960-894x(00)00114-1

  日期：2000.5

  In order to develop new inhibitors of NF-kappa B activation, we designed and synthesized dehydroxymethyl derivatives of epoxyquinomicin C, namely, DHM2EQ and its regioisomer DHM3EQ. These derivatives were synthesized from 2,5-dimethoxyaniline in 5 steps. Since DHM2EQ was more active and less toxic than DHM3EQ, its stereochemical configuration was determined by X-ray crystallographic analysis. Each enantiomer of the protected DHM2EQ was separated by a chiral column and deprotected. DHM2EQ inhibited TNF-alpha-induced activation of NF-kappa B in human T cell leukemia cells, and also inhibited collagen-induced arthritis in a rheumatoid model in mice. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Preparation and biological activities of optically active dehydroxymethylepoxyquinomicin, a novel NF-κB inhibitor
  作者：Yoshikazu Suzuki、Chie Sugiyama、Osamu Ohno、Kazuo Umezawa

  DOI：10.1016/j.tet.2004.01.103

  日期：2004.8

  NF-kappaB is a transcription factor that induces inflammatory cytokines and anti-apoptotic proteins. We have designed a new NF-kappaB inhibitor based on the structure of the antibiotic epoxyquinomicin C. The designed compound, dehydroxymethylepoxyquinomicin (DHMEQ) was synthesized as a racemic form from 2,5-dimethoxyaniline through 5 steps. Application of racemic DHMEQ onto the chiral column (Chiralpak AD) directly gave enantiomeric DHMEQ after purification. (-)-DHMEQ was more potent than its enantiomer. (-)-DHMEQ was found to inhibit NF-kappaB activity and macrophage differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in human monocyte THP-1 cells. (C) 2004 Elsevier Ltd. All rights reserved.