(4-金刚烷-1-基苯氧基)乙酸 | 52804-26-9

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (4-金刚烷-1-基苯氧基)乙酸
• 中文别名: 2-(4-(1-金刚烷)苯氧基)乙酸
• 英文名称: (4-adamantan-1-yl-phenoxy)acetic acid
• 英文别名: 2-(4-(adamantan-1-yl)phenoxy)acetic acid；4-(1-adamantyl)phenoxyacetic acid；[4-(1-Adamantyl)phenoxy]acetic acid；2-[4-(1-adamantyl)phenoxy]acetic acid
• CAS: 52804-26-9
• 化学式: C₁₈H₂₂O₃
• mdl: MFCD00168197
• 分子量: 286.371
• InChiKey: WIWCHWGNONICJI-UHFFFAOYSA-N

物化性质

• 熔点：
  168-170℃ (acetic acid water )
• 沸点：
  441.1±28.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2918990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  存放于室温、干燥环境中，并请密封保存。

反应信息

• 作为反应物：
  描述：

  (4-金刚烷-1-基苯氧基)乙酸 在 盐酸 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 9.0h， 生成 2-(4-adamantan-1-yl-phenoxymethyl)-1H-benzoimidazole-5 carboxylic acid
  参考文献：
  名称：

  Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors

  摘要：

  A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC50 = 4.4 mu M) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.046
• 作为产物：
  描述：

  (4-adamantan-1-ylphenoxy)acetic acid ethyl ester 在 lithium hydroxide 作用下， 反应 12.0h， 以65%的产率得到(4-金刚烷-1-基苯氧基)乙酸
  参考文献：
  名称：

  茚并 [1, 2-c] 吡唑衍生物作为线粒体苹果酸脱氢酶 2 (MDH2) 抑制剂的合成、生物学评价和分子对接研究

  摘要：

  缺氧诱导因子-1 (HIF-1) 是一种关键的转录因子，与血管生成、肿瘤存活、转移和细胞增殖的诱导密切相关，使其成为实体瘤治疗药物的关键治疗靶点。在此，设计了一系列新的多功能化学探针，包括主基团，即。金刚烷基和茚，位于母体化合物 LW6 的不同位置。对设计的化合物及其与 HIF-1α 和苹果酸脱氢酶 2 (MDH2) 的关系进行了分子对接研究。我们的化合物对 MDH2 的抑制预计会降低 NADH 水平。事实上，对乳腺癌细胞系 4T1 的治疗导致 NADH 浓度的强烈降低。(E)-3-(4-((3r, 5r,50  = 59 nM），并且在缺氧条件下具有最佳抑制潜力（MCF-7：IC 50  = 57 nM）。该化合物还给出了最高的对接之一“高于在初始对接运行中使用 LW6 获得的分数（-31.63 kcal/mol）（PDB 代码：4WLO）。从对接结果中还合成了其他收率良好的相关化合物，

  DOI：

  10.1016/j.bioorg.2021.104779

文献信息

• Plasminogen Activator Inhibitor-1 Inhibitor
  申请人：Miyata Toshio

  公开号：US20120022080A1

  公开（公告）日：2012-01-26

  The present invention provides a novel compound having plasminogen activator inhibitor-1 inhibitory activity, and an inhibitor of PAI-1 comprising the compound as an active ingredient. The present invention also provides a pharmaceutical composition having an inhibitory action on PAI-1 activity and being efficacious in the prevention and treatment of various diseases whose onset is associated with PAI-1 activity.

  本发明提供了一种具有纤溶酶原激活物抑制剂-1抑制活性的新化合物，以及包括该化合物作为活性成分的PAI-1抑制剂。本发明还提供了一种对PAI-1活性具有抑制作用且在预防和治疗与PAI-1活性相关的各种疾病方面有效的药物组合物。
• Methyl 3-(3-(4-(2,4,4-Trimethylpentan-2-yl)phenoxy)-propanamido)benzoate as a Novel and Dual Malate Dehydrogenase (MDH) 1/2 Inhibitor Targeting Cancer Metabolism
  作者：Ravi Naik、Hyun Seung Ban、Kyusic Jang、Inhyub Kim、Xuezhen Xu、Dipesh Harmalkar、Seong-Ah Shin、Minkyoung Kim、Bo-Kyung Kim、Jaehyung Park、Bonsu Ku、Sujin Oh、Misun Won、Kyeong Lee

  DOI：10.1021/acs.jmedchem.7b01231

  日期：2017.10.26

  factor (HIF)-1 inhibitor LW6 containing an (aryloxyacetylamino)benzoic acid moiety inhibits malate dehydrogenase 2 (MDH2) using a chemical biology approach. Structure–activity relationship studies on a series of (aryloxyacetylamino)benzoic acids identified selective MDH1, MDH2, and dual inhibitors, which were used to study the relationship between MDH enzyme activity and HIF-1 inhibition. We hypothesized

  以前，我们报道了使用化学生物学方法，含有（芳氧基乙酰氨基）苯甲酸部分的缺氧诱导因子（HIF）-1抑制剂LW6抑制苹果酸脱氢酶2（MDH2）。对一系列（芳氧基乙酰氨基）苯甲酸的结构-活性关系研究确定了选择性MDH1，MDH2和双重抑制剂，这些抑制剂用于研究MDH酶活性与HIF-1抑制之间的关系。我们假设对MDH1和MDH2的双重抑制可能是靶向癌症代谢的有力方法，并且选择了3-（3-（4-（2,4,4-三甲基戊烷-2-基）苯氧基）丙酰胺基）-苯甲酸甲酯（16c）作为最有效的双重抑制剂。动力学研究表明，化合物16c竞争性抑制MDH1和MDH2。化合物16c抑制线粒体呼吸和缺氧诱导的HIF-1α积累。在使用HCT116细胞的异种移植测定中，化合物16c表现出显着的体内抗肿瘤功效。这一发现提供了具体的证据，即抑制MDH1和MDH2可能为开发针对癌症代谢和肿瘤生长的新型疗法提供有价值的平台。
• NOVEL COMPOUNDS AS HIF-1ALPHAINHIBITORS AND MANUFACTURING PROCESS THEREOF
  申请人：KOREA RESEARCH INSTITUTE OF BIOSCIENCE AND BIOTECHNOLOGY

  公开号：US20140228357A1

  公开（公告）日：2014-08-14

  The present invention relates to novel compounds as HIF-1α inhibitors, manufacturing process thereof, and a pharmaceutical compositions. The compounds according to the present invention having inhibition activity against HIF-1α, can be used as a therapeutic prevention and/or treatment for various solid cancers such as colon cancer, liver cancer, stomach cancer and breast cancer. Also, the compounds according to the present invention are useful in the treatment of diabetic retinopathy and rheumatoid arthritis, which are aggravated by HIF-1α-mediated VEGFA expression.

  本发明涉及作为HIF-1α抑制剂的新化合物，其制造工艺以及药物组合物。根据本发明的化合物具有对HIF-1α的抑制活性，可用作治疗预防和/或治疗各种实体癌症，如结肠癌、肝癌、胃癌和乳腺癌。此外，根据本发明的化合物在治疗由HIF-1α介导的VEGFA表达加重的糖尿病视网膜病变和类风湿性关节炎方面具有用处。
• COMPOUNDS THAT INHIBIT HIF-1 ACTIVITY, THE METHOD FOR PREPARATION THEREOF AND THE PHARMACEUTICAL COMPOSITION CONTAINING THEM AS AN EFFECTIVE COMPONENT
  申请人：Lee Jung Joon

  公开号：US20090306078A1

  公开（公告）日：2009-12-10

  Disclosed herein are an HIF-1 inhibitor, a method for the preparation thereof, and a pharmaceutical composition comprising the same as an active ingredient. The HIF-1 inhibitor shows anticancer activity thanks to the inhibition activity against HIF-1, a transcription factor which plays an important role in the growth and metastasis of cancer, but not to general cytotoxicity. Thus, the HIF-inhibitor and a pharmaceutically acceptable salt thereof can be used as a therapeutic for various cancers such as liver cancer; stomach cancer and breast cancer. Also, the compound having inhibition activity against HIF-1 is useful in the treatment of diabetic retinopathy and arthritis, which are aggravated by HIF-1-mediated VEGF expression.

  本文披露了一种HIF-1抑制剂，其制备方法，以及包含其作为活性成分的药物组合物。该HIF-1抑制剂显示抗癌活性，这归功于其对HIF-1的抑制活性，HIF-1是一种在癌症生长和转移中起重要作用的转录因子，但不具有一般细胞毒性。因此，HIF抑制剂及其药用可接受的盐可用作治疗各种癌症，如肝癌、胃癌和乳腺癌的治疗药物。此外，具有对HIF-1抑制活性的化合物在治疗由HIF-1介导的VEGF表达加重的糖尿病视网膜病变和关节炎方面是有用的。
• NOVEL COMPOUND HAVING MALATE DEHYDROGENASE INHIBITORY ACTIVITY AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER COMPRISING SAME AS ACTIVE INGREDIENT
  申请人：DONGGUK UNIVERSITY GYEONGJU CAMPUS INDUSTRY-ACADEMY COOPERATION FOUNDATION

  公开号：US20200031764A1

  公开（公告）日：2020-01-30

  The present invention relates to a compound exhibiting inhibitory activity of at least one of malate dehydrogenases I (MDH1) and malate dehydrogenases 2 (MDH2), and a pharmaceutical composition for preventing or treating cancer comprising the same as an active ingredient. The inventors of the present invention have experimentally confirmed that the compound exhibiting the MDH1 and/or MDH2 inhibitory activity has an inhibitory effect on mitochondrial respiration in cancer cells, an excellent inhibitory effect on cancer cell growth, etc. Thus, the compound of the present invention is expected to be effectively used as a pharmaceutical composition for treating cancer.

  本发明涉及一种对苹果酸脱氢酶I（MDH1）和/或苹果酸脱氢酶2（MDH2）至少一种具有抑制活性的化合物，以及包含该化合物作为活性成分的用于预防或治疗癌症的药物组合物。本发明的发明人通过实验证实，表现出MDH1和/或MDH2抑制活性的该化合物对癌细胞线粒体呼吸具有抑制作用，对癌细胞生长具有优异的抑制效果等。因此，本发明的化合物有望被有效地用作治疗癌症的药物组合物。