4,6-dioxo-6-(4-methylphenyl)hexanoic acid | 114150-50-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4,6-dioxo-6-(4-methylphenyl)hexanoic acid
• 英文别名: 6-(4-methylphenyl)-4,6-dioxohexanoic acid；4,6-dioxo-6-p-tolylhexanoic acid
• CAS: 114150-50-4
• 化学式: C₁₃H₁₄O₄
• 分子量: 234.252
• InChiKey: SMJXPAZNGZSPNV-UHFFFAOYSA-N

物化性质

• 熔点：
  139-141 °C
• 沸点：
  428.5±25.0 °C(predicted)
• 密度：
  1.201±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  71.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,6-dioxo-6-(4-methylphenyl)hexanoic 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 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 57.0h， 生成 N-((5-carboxy-X-rhodaminyl)but-4-yl)-3-(1-(4-methoxyphenyl)-5-(p-tolyl)-1H-pyrazol-3-yl)propenamide
  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：

  丁二酸酐 、 对甲基苯乙酮 生成 4,6-dioxo-6-(4-methylphenyl)hexanoic acid
  参考文献：
  名称：

  吡唑-3-丙酸衍生物作为人类嗜中性白细胞中白三烯生物合成的新型抑制剂

  摘要：

  我们最近提出，化合物4a – b适度抑制人类嗜中性白细胞中白三烯（LT）的形成。对于结构衍生4A - b，合成并导致在由例示化合物活化人中性粒细胞LT的生物合成更有效抑制新颖36标题化合物15，27-30，32-37，41，42与IC 50个值在范围为1.6–3.5μM。此外，化合物32，35，42，43和44显示出对血小板COX-1活性的显着抑制，IC 50分别为2.5、0.041、0.3、0.9和0.014μM，从而导致了双重作用的抑制剂。基于它们在细胞环境中的高效力，这些简单的吡唑-3-丙酸衍生物可能在设计更有效的化合物中具有潜力，可用于治疗炎症和过敏性疾病。

  DOI：

  10.1016/j.ejmech.2011.08.009

文献信息

• Methods and compositions for diagnostic and therapeutic targeting of COX-2
  申请人：Marnett J. Lawrence

  公开号：US20070292352A1

  公开（公告）日：2007-12-20

  The presently disclosed subject matter provides compositions that selectively bind cyclooxygenase-2 and comprise a therapeutic and/or diagnostic moiety. Also provided are methods for using the disclosed compositions for diagnosing (i.e., by imaging) a target cell and/or treating a disorder associated with a cyclooxygenase-2 biological activity.

  目前公开的主题提供了选择性结合环氧合酶-2并包含治疗和/或诊断基团的组合物。还提供了使用公开的组合物进行诊断（即通过成像）目标细胞和/或治疗与环氧合酶-2生物活性相关的疾病的方法。
• 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
• METHODS AND COMPOSITIONS FOR DIAGNOSTIC AND THERAPEUTIC TARGETING OF COX-2
  申请人：Marnett Lawrence J.

  公开号：US20130052138A1

  公开（公告）日：2013-02-28

  The presently disclosed subject matter provides compositions that selectively bind cyclooxygenase-2 and comprise a therapeutic and/or diagnostic moiety. Also provided are methods for using the disclosed compositions for diagnosing (i.e., by imaging) a target cell and/or treating a disorder associated with a cyclooxygenase-2 biological activity.

  目前披露的主题提供了选择性结合环氧合酶-2并包含治疗和/或诊断部分的组合物。还提供了使用所披露的组合物进行诊断（即通过成像）靶细胞和/或治疗与环氧合酶-2生物活性相关的疾病的方法。
• Regioselective synthesis of 1,5-diaryl pyrazole anti-inflammatory agents
  申请人：ORTHO PHARMACEUTICAL CORPORATION

  公开号：EP0534800A2

  公开（公告）日：1993-03-31

  The invention provides a process for preparing 1,5-diaryl pyrazole anti-inflammatory agents. A 6-aryl-4,6-dioxohexanoic acid is treated with acetic anhydride or acetyl chloride to produce an enol lactone, which is added to methylhydroxylamine to generate the dione hydroxamic acid. This dione hydroxamic acid is then treated with 4-methoxyphenylhydrazine hydrochloride to yield the 1,5-diaryl pyrazole. Novel intermediate compounds in the synthetic pathway are also disclosed.

  本发明提供了一种制备 1,5-二芳基吡唑消炎剂的工艺。用乙酸酐或乙酰氯处理 6-芳基-4,6-二氧代己酸，生成烯醇内酯，将其加入甲基羟胺，生成二酮羟肟酸。然后用 4-甲氧基苯肼盐酸盐处理这种二酮羟肟酸，生成 1,5-二芳基吡唑。此外，还公开了合成途径中的新型中间化合物。
• 3-[1-(4-Sulfamoylphenyl)-5-<i>p</i>-tolyl-1<i>H</i>-pyrazol-3-yl]propanoic acid and 3-[5-(4-bromophenyl)-1-(4-sulfamoylphenyl)-1<i>H</i>-pyrazol-3-yl]propanoic acid–dichloromethane–diethyl ether–water (2/0.72/1/1)
  作者：Isuru R. Kumarasinghe、Victor J. Hruby、Gary S. Nichol

  DOI：10.1107/s010827010901676x

  日期：2009.6.15

  The syntheses of 3-[1-(4-sulfamoylphenyl)-5-p-tolyl-1H-pyrazol-3- yl]propanoic acid, C19H19N3O4S, (I), and 3-[5-(4-bromo phenyl)-1-(4-sulfamoylphenyl)-1H-pyrazol-3-yl] propanoic acid-dichloromethane-diethyl ether-water (2/0.72/1/1), 2C(18)H(16)BrN(3)O(4)S center dot 0.72CH(2)Cl(2) center dot C4H10O center dot H2O, (II), are regio-specific. However, correct identification by spectroscopic techniques of the regioisomer formed is not trivial and single-crystal X-ray analysis provided the only means of unambiguous structure determination. Both structures make extensive use of hydrogen bonding and while compound (I) forms a straightforward unsolvated Z' = 1 structure, compound (II) crystallizes as an unusual mixed solvate, with two crystallographically unique molecules of the pyrazole derivative present in the asymmetric unit. The structure of (II) also features Br center dot center dot center dot Br interactions.