ethyl 2-(2-isopropylphenoxy)acetate | 444613-15-4

• 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: ethyl 2-(2-isopropylphenoxy)acetate
• 英文别名: Ethyl 2-(2-propan-2-ylphenoxy)acetate
• CAS: 444613-15-4
• 化学式: C₁₃H₁₈O₃
• mdl: MFCD03900653
• 分子量: 222.284
• InChiKey: CYMQLVKNVKRVAX-UHFFFAOYSA-N

物化性质

• 沸点：
  301.0±25.0 °C(Predicted)
• 密度：
  1.026±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 2-(2-isopropylphenoxy)acetate 在 2,6-二甲基吡啶 、 乙醇 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 1H‑indole‑2‑carboxylic acid {2‑[2‑(2‑isopropyl‑phenoxy)‑acetylamino]‑phenyl}‑amide
  参考文献：
  名称：

  Targeting HIF-1α by newly synthesized Indolephenoxyacetamide (IPA) analogs to induce anti-angiogenesis-mediated solid tumor suppression

  摘要：

  低氧微环境是实体瘤的常见特征，它促进了癌症的发展。在低氧条件下表达的转录因子HIF-1α刺激肿瘤血管生成，使HIF-1α成为一个有前景的抗癌剂。另一方面，合成吲哚酚氧乙酰胺衍生物以其药理潜力而闻名。基于此背景，我们合成了新型IPA（8a-n）类似物，并验证了其抗肿瘤活性。新系列的IPA（8a-n）通过多步骤反应序列合成，并基于不同的光谱分析FT-IR、1H、13C NMR、质谱和元素分析进行表征。通过MTT assay评估了IPA（8a-n）的基于细胞的筛选。通过CAM、大鼠角膜、管形成和迁移实验验证了IPA（8k）的抗血管生成效果。通过酶谱和IB研究验证了其分子机制。在DLA实体瘤模型中测量了体内抗肿瘤活性。进行抗增殖研究筛选，结果显示IPA（8k）是一个领先分子，其IC50值约为5μM。抗血管生成实验揭示了通过抑制HIF-1α和调节下游调节基因VEGF、MMPs和P53来预防血管生成的活性。在体内实体瘤模型中得到了确认的结果。IPA（8k）是一个强效的抗增殖分子，具有抗血管生成活性，并特异性地靶向HIF1α，从而调节其下游调节基因在体外和体内。该研究为针对HIF-1α的针对特定靶点的新药开发提供了范围，用于治疗实体瘤。

  DOI：

  10.1007/s43440-021-00266-8
• 作为产物：
  描述：

  异丙苯酚 、 氯乙酸乙酯 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以85%的产率得到ethyl 2-(2-isopropylphenoxy)acetate
  参考文献：
  名称：

  Targeting HIF-1α by newly synthesized Indolephenoxyacetamide (IPA) analogs to induce anti-angiogenesis-mediated solid tumor suppression

  摘要：

  低氧微环境是实体瘤的常见特征，它促进了癌症的发展。在低氧条件下表达的转录因子HIF-1α刺激肿瘤血管生成，使HIF-1α成为一个有前景的抗癌剂。另一方面，合成吲哚酚氧乙酰胺衍生物以其药理潜力而闻名。基于此背景，我们合成了新型IPA（8a-n）类似物，并验证了其抗肿瘤活性。新系列的IPA（8a-n）通过多步骤反应序列合成，并基于不同的光谱分析FT-IR、1H、13C NMR、质谱和元素分析进行表征。通过MTT assay评估了IPA（8a-n）的基于细胞的筛选。通过CAM、大鼠角膜、管形成和迁移实验验证了IPA（8k）的抗血管生成效果。通过酶谱和IB研究验证了其分子机制。在DLA实体瘤模型中测量了体内抗肿瘤活性。进行抗增殖研究筛选，结果显示IPA（8k）是一个领先分子，其IC50值约为5μM。抗血管生成实验揭示了通过抑制HIF-1α和调节下游调节基因VEGF、MMPs和P53来预防血管生成的活性。在体内实体瘤模型中得到了确认的结果。IPA（8k）是一个强效的抗增殖分子，具有抗血管生成活性，并特异性地靶向HIF1α，从而调节其下游调节基因在体外和体内。该研究为针对HIF-1α的针对特定靶点的新药开发提供了范围，用于治疗实体瘤。

  DOI：

  10.1007/s43440-021-00266-8

文献信息

• NOVEL HETEROARYL COMPOUND, ENANTIOMER, DIASTEREOMER OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND ANTIVIRAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT
  申请人：INSTITUT PASTEUR KOREA

  公开号：US20200031816A1

  公开（公告）日：2020-01-30

  The present invention relates to a novel heteroaryl compound, an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof, and an antiviral composition comprising the same as an active ingredient. The novel compounds represented by formula (I) or formula (II) according to the present invention are remarkably superior in antiviral activity against an influenza virus, and furthermore, have low cytotoxicity and thus low adverse effects on a human body. Therefore, a pharmaceutical composition containing the same as an active ingredient can be effectively used for the prevention or treatment of diseases caused by an influenza virus infection.

  本发明涉及一种新型杂环芳基化合物，其对映异构体、顺异构体或其药学上可接受的盐，以及包含其作为活性成分的抗病毒组合物。根据本发明的化合物代表的新型化合物（I）或化合物（II）在抗流感病毒活性方面明显优越，并且具有低细胞毒性，因此对人体的不良影响较低。因此，含有该化合物作为活性成分的药物组合物可有效用于预防或治疗由流感病毒感染引起的疾病。
• Modulation of DNA damage response by targeting ATM kinase using newly synthesized di-phenoxy acetamide (DPA) analogs to induce anti-neoplasia
  作者：Fares Hezam Al-Ostoot、Ankith Sherapura、Vikas H. Malojirao、Prabhu Thirusangu、Tahani I. Al-Muhimeed、Shaukath Ara Khanum、B. T. Prabhakar

  DOI：10.1007/s43440-021-00292-6

  日期：2021.10

  Imbalance and instability in the structure of the DNA have become major characteristics of cancer. In response to DNA damage, DNA damage response (DDR) protein, ataxia telangiectasia mutated (ATM), plays a pivotal role in the modulation of regulatory regions responsible for inhibition of apoptosis, thereby neoplastic progression. A new series of DPA (7a–t) were synthesized, characterized. Anti-proliferative studies to identify the lead compound were carried out by LDH and MTT assay. Apoptosis/DNA damage was measured through FACS, Annexin-v staining, TUNEL and Comet assay. Elucidation of molecular mechanism through immunoblot and further validation of the drug effect through in vivo approaches. Initial in vitro anti-proliferative screening of Compounds DPA (7a–t) against multiple cancer cell lines identified Compound DPA (7n) as a potent cytotoxic molecule with IC50 value of 4.3 μM. Down the line, in vitro and in vivo evaluation of Compound DPA (7n) inferred that it has apoptotic inducing potentiality. Further, evaluation of molecular mechanism inferred that Compound DPA (7n) effectively modulates ATM phosphorylation only, eventually altering downstream signalling pathways. Compound DPA (7n) emerged as a potent proapoptotic and anti-neoplastic agent by inhibiting ATM kinase activity both in vitro and in vivo. The conferring results ascertain that the drug could be developed as a new ATM kinase inhibitor with anti-cancer capacity.

  DNA结构的失衡和不稳定性已成为癌症的主要特征。在应对DNA损伤时，DNA损伤反应（DDR）蛋白，共济失调毛细血管扩张突变（ATM）在调节负责抑制凋亡的调控区域中发挥着关键作用，从而促进肿瘤进展。合成了一系列新的DPA（7a–t）并进行了特征化。通过LDH和MTT assay进行抗增殖研究以鉴定先导化合物。通过FACS、 Annexin-v染色、TUNEL和Comet assay测量凋亡/DNA损伤。通过免疫印迹阐明分子机制，并通过体内方法进一步验证药物效果。对化合物DPA（7a–t）进行的初步体外抗增殖筛选针对多种癌细胞系，鉴定出化合物DPA（7n）为一种强效细胞毒性分子，其IC50值为4.3μM。通过化合物DPA（7n）的体外和体内评估推断其具有诱发凋亡的潜力。进一步评估分子机制推断化合物DPA（7n）仅有效地调节ATM磷酸化，最终改变下游信号传导途径。化合物DPA（7n）在体外和体内抑制ATM激酶活性，展现出强大的促凋亡和抗肿瘤特性。这些结果确认该药物可能被开发为具有抗癌能力的新型ATM激酶抑制剂。
• New Triazine Derivatives as Serotonin 5-HT6 Receptor Ligands
  作者：Dorota Łażewska、Małgorzata Więcek、Grzegorz Satała、Paulina Chałupnik、Ewa Żesławska、Ewelina Honkisz-Orzechowska、Monika Tarasek、Gniewomir Latacz、Wojciech Nitek、Ewa Szymańska、Jadwiga Handzlik

  DOI：10.3390/molecules28031108

  日期：——

  hylphenoxy)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine), the potent 5-HT6R antagonist (Ki = 11 nM) with promising ADMET and in vivo properties, were designed. The synthesized compounds were tested for their affinity towards 5-HT6R and other receptor (off)targets (serotonin 5-HT2A, 5-HT7 and dopamine D2). Based on the new results, 4-(2-tert-butylphenoxy)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine

  由于患有阿尔茨海默病 (AD) 的人数持续上升，迫切需要新的有效药物，不仅可以减缓疾病的进展，而且可以阻止甚至阻止其发展。血清素 5-HT6 受体 (5-HT6R) 配体仍然是治疗 AD 的有前途的治疗靶点。1,3,5-三嗪衍生物作为缺少吲哚或砜基团的新型结构，已被证明是该受体的有效配体。在目前的工作中，化合物 MST4 (4-((2-isopropyl-5-methylphenoxy)methyl)-6-(4-methylpiperazin-1-yl)-1,3,5-triazin-2-amine) 的新衍生物, 设计了具有有前途的 ADMET 和体内特性的强效 5-HT6R 拮抗剂 (Ki = 11 nM)。测试了合成化合物对 5-HT6R 和其他受体（关闭）靶标（血清素 5-HT2A，5-HT7 和多巴胺 D2)。基于新的结果，选择 4-(2-tert-butylphenoxy)-6-
• Heteroaryl compound, enantiomer, diastereomer or pharmaceutically acceptable salt thereof, and antiviral composition containing same as active ingredient
  申请人：INSTITUT PASTEUR KOREA

  公开号：US11149033B2

  公开（公告）日：2021-10-19

  The present invention relates to a novel heteroaryl compound, an enantiomer, a diastereomer or a pharmaceutically acceptable salt thereof, and an antiviral composition comprising the same as an active ingredient. The novel compounds represented by formula (I) or formula (II) according to the present invention are remarkably superior in antiviral activity against an influenza virus, and furthermore, have low cytotoxicity and thus low adverse effects on a human body. Therefore, a pharmaceutical composition containing the same as an active ingredient can be effectively used for the prevention or treatment of diseases caused by an influenza virus infection.

  本发明涉及一种新型杂芳基化合物、其对映体、非对映体或其药学上可接受的盐，以及以其为活性成分的抗病毒组合物。根据本发明，由式（I）或式（II）代表的新型化合物在抗流感病毒活性方面具有显著优势，而且细胞毒性低，因此对人体的不良影响小。因此，以其为活性成分的药物组合物可有效地用于预防或治疗由流感病毒感染引起的疾病。
• The anti-invasive role of novel synthesized pyridazine hydrazide appended phenoxy acetic acid against neoplastic development targeting matrix metallo proteases
  作者：Yasser Hussein Eissa Mohammed、Prabhu Thirusangu、Zabiulla、Vigneshwaran V、Prabhakar B.T、Shaukath Ara Khanum

  DOI：10.1016/j.biopha.2017.08.105

  日期：2017.11

  Neoplastic metastasis is a major process where tumor cells migrate from the primary tumor and colonize at other parts of our body to form secondary tumor. Cancer incidences are rising and novel anti-neoplastic compounds with new mechanism of actions are essential for preventing cancer related deaths. In the current examination, a novel series of pyridazine analogues 6a-l was synthesized and evaluated against metastatic neoplastic cells. Experimental data postulated compound 6j has potential cytotoxic efficacy with prolonged activity against various cancer cells, including A549, HepG2, A498, CaSki and SiHa cells. Moreover, compound 6j arrests the A549 migration and invasions markedly by counteracting matrix metalloproteinase (MMP)-2 and MMP-9 expressions. Also, compound 6j proved its potentiality against Dalton's solid lymphoma progression in-vivo by abridging MVD and MMP expressions. Compound 6j interacts with MMP-2 and MMP-9 by H-bond in-silico, thereby down regulates the MMPs action in tumourigenesis. Altogether, we concluded that compound 6j down regulates MMP-2 and MMP-9 and thereby impairs metastatic cancer cell migration and invasions which can be translated into a potent anti-neoplastic agent.