3-(1-(4-methoxyphenyl)-5-(p-tolyl)-1H-pyrazol-3-yl)propanoic acid | 114150-36-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(1-(4-methoxyphenyl)-5-(p-tolyl)-1H-pyrazol-3-yl)propanoic acid
• 英文别名: 3-[1-(4-Methoxyphenyl)-5-(4-methylphenyl)pyrazol-3-yl]propanoic acid
• CAS: 114150-36-6
• 化学式: C₂₀H₂₀N₂O₃
• 分子量: 336.39
• InChiKey: PMCIMSNZSUUYNA-UHFFFAOYSA-N

物化性质

• 熔点：
  145-147 °C
• 沸点：
  531.1±50.0 °C(predicted)
• 密度：
  1.18±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  64.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(1-(4-methoxyphenyl)-5-(p-tolyl)-1H-pyrazol-3-yl)propanoic acid 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 N-(4-aminobutyl)-3-(1-(4-methoxyphenyl)-5-(p-tolyl)-1H-pyrazol-3-yl)propenamide hydrochloride
  参考文献：
  名称：

  Targeted Detection of Cyclooxygenase-1 in Ovarian Cancer

  摘要：

  Overexpression of cyclooxygenase-1 (COX-1) is associated with the initiation and progression of ovarian cancer, and targeted imaging of COX-1 is a promising strategy for early detection of this disease. We report the discovery of N-[(5-carboxy-X-rhodaminyl)but-4-yl]-3-(1-(4-methoxyphenyl)-5-(p-tolyl)-1H-pyrazol-3-yl)propenamide (CMP) as the first COX-1-targeted optical agent for imaging of ovarian cancer. CMP exhibits light emission at 604 nm (lambda(max)), thereby minimizing tissue autofluorescence interference. In both purified enzyme and COX-1-expressing human ovarian adenocarcinoma (OVCAR-3) cells, CMP inhibits COX-1 at low nanomolar potencies (IC50 = 94 and 44 nM, respectively). CMP's selective binding to COX-1 in OVCAR-3 cells was visualized microscopically as intense intracellular fluorescence. In vivo optical imaging of xenografts in athymic nude mice revealed COX-1-dependent accumulation of CMP in COX-1-expressing mouse ovarian surface epithelial carcinoma (ID8NGL) and OVCAR-3 cells. These results establish proof-of-principle for the feasibility of targeting COX-1 in the development of new imaging and therapeutic strategies for ovarian cancer.

  DOI：

  10.1021/acsmedchemlett.9b00280
• 作为产物：
  描述：

  对甲基苯乙酮 在 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 甲醇 为溶剂， 反应 7.5h， 生成 3-(1-(4-methoxyphenyl)-5-(p-tolyl)-1H-pyrazol-3-yl)propanoic acid
  参考文献：
  名称：

  The Regioselective Synthesis of Tepoxalin, 3-[5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-pyrazolyl]-N-hydroxy-N-methylpropanamide and Related 1,5-Diarylpyrazole Anti-inflammatory Agents

  摘要：

  Tepoxalin及其类似物(二芳基吡唑基丙酸)的合成方法: 1. 将芳基肼盐酸盐与6-芳基-4,6-二氧代己酸在醇溶剂中,在碱性催化剂作用下缩合。 2. 生成的二芳基吡唑基丙酸可以转化为其N-甲基羟胺酸: - 首先生成相应的酰氯 - 然后与N-甲基羟胺反应

  DOI：

  10.1055/s-1991-26367

文献信息

• The Regioselective Synthesis of Tepoxalin, 3-[5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-pyrazolyl]-<i>N</i>-hydroxy-<i>N</i>-methylpropanamide and Related 1,5-Diarylpyrazole Anti-inflammatory Agents
  作者：William Murray、Michael Wachter、Donald Barton、Yolanda Forero-Kelly

  DOI：10.1055/s-1991-26367

  日期：——

  Tepoxalin, a potent anti-inflammatory agent, and its analogs can be synthesized by condensing an appropriate arylhydrazine hydrochloride and a 6-aryl-4,6-dioxohexanoic acid in alcohol with a base catalyst. These diarylpyrazolylpropanoic acids can be converted to their N-methylhydroxamic acids by generating the requisite acid chloride, and allowing it to react with N-methylhydroxylamine.

  Tepoxalin及其类似物(二芳基吡唑基丙酸)的合成方法: 1. 将芳基肼盐酸盐与6-芳基-4,6-二氧代己酸在醇溶剂中,在碱性催化剂作用下缩合。 2. 生成的二芳基吡唑基丙酸可以转化为其N-甲基羟胺酸: - 首先生成相应的酰氯 - 然后与N-甲基羟胺反应
• MURRAY, WILLIAM V.;WACHTER, MICHAEL P.
  作者：MURRAY, WILLIAM V.、WACHTER, MICHAEL P.

  DOI：——

  日期：——
• WACHTER, MICHAEL P.;FERRO, MICHAEL P.
  作者：WACHTER, MICHAEL P.、FERRO, MICHAEL P.

  DOI：——

  日期：——
• US5164381A
  申请人：——

  公开号：US5164381A

  公开（公告）日：1992-11-17
• Targeted Detection of Cyclooxygenase-1 in Ovarian Cancer
  作者：Paola Malerba、Brenda C. Crews、Kebreab Ghebreselasie、Cristina K. Daniel、Elma Jashim、Ansari M. Aleem、Redoan A. Salam、Lawrence J. Marnett、Md. Jashim Uddin

  DOI：10.1021/acsmedchemlett.9b00280

  日期：2020.10.8

  Overexpression of cyclooxygenase-1 (COX-1) is associated with the initiation and progression of ovarian cancer, and targeted imaging of COX-1 is a promising strategy for early detection of this disease. We report the discovery of N-[(5-carboxy-X-rhodaminyl)but-4-yl]-3-(1-(4-methoxyphenyl)-5-(p-tolyl)-1H-pyrazol-3-yl)propenamide (CMP) as the first COX-1-targeted optical agent for imaging of ovarian cancer. CMP exhibits light emission at 604 nm (lambda(max)), thereby minimizing tissue autofluorescence interference. In both purified enzyme and COX-1-expressing human ovarian adenocarcinoma (OVCAR-3) cells, CMP inhibits COX-1 at low nanomolar potencies (IC50 = 94 and 44 nM, respectively). CMP's selective binding to COX-1 in OVCAR-3 cells was visualized microscopically as intense intracellular fluorescence. In vivo optical imaging of xenografts in athymic nude mice revealed COX-1-dependent accumulation of CMP in COX-1-expressing mouse ovarian surface epithelial carcinoma (ID8NGL) and OVCAR-3 cells. These results establish proof-of-principle for the feasibility of targeting COX-1 in the development of new imaging and therapeutic strategies for ovarian cancer.