5-(6-甲氧基萘-2-基)吡啶-3-甲酸甲酯 | 1050646-35-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 5-(6-甲氧基萘-2-基)吡啶-3-甲酸甲酯
• 英文名称: methyl 5-(6-methoxynaphthalen-2-yl)pyridine-3-carboxylate
• 英文别名: methyl 5-(6-methoxynaphthalen-2-yl)nicotinate；methyl 5-[6-(methyloxy)-2-naphthalenyl]-3-pyridinecarboxylate
• CAS: 1050646-35-9
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: CBEZYLKPJKSBRY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(6-甲氧基萘-2-基)吡啶-3-甲酸甲酯 在 三溴化硼 、 水 作用下， 以 二氯甲烷 为溶剂， 以27%的产率得到methyl 5-(6-hydroxy-2-naphthalenyl)-3-pyridinecarboxylate
  参考文献：
  名称：

  [EN] FARNESOID X RECEPTOR AGONISTS
  [FR] AGONISTES DU RÉCEPTEUR DE FARNÉSOÏDE X

  摘要：

  本发明涉及法内索德X受体（FXR，NR1H4）。FXR是配体激活的转录因子核受体类的一个成员。更具体地说，本发明涉及作为FXR激动剂的化合物，包含该化合物的药物制剂，以及同一治疗用途。新颖的异恶唑化合物被披露作为药物组合物的一部分，用于治疗由FXR活性降低介导的状况，如肥胖、糖尿病、胆汁淤积性肝病、肝纤维化和代谢综合征。

  公开号：

  WO2009005998A1
• 作为产物：
  描述：

  2-溴-6-甲氧基萘 在 potassium fluoride 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.34h， 生成 5-(6-甲氧基萘-2-基)吡啶-3-甲酸甲酯
  参考文献：
  名称：

  Synthesis of Aryl-Substituted Naphthalenoids as Potent Topoisomerase Inhibitors

  摘要：

  我们设计并合成了十二种新的芳基取代萘类化合物（1-7、9、10 和 13-16）以及四种已知的萘类化合物（8 和 11-13）。在人乳腺癌 MDA-MB-231、人肺癌 A549 和人宫颈癌 HeLa 细胞系上，通过磺基罗丹明 B 检测法评估了这些化合物的抗肿瘤活性。四种化合物（2、4、10 和 12）对这三种细胞株的生长都有很强的抑制作用，IC50 在 0.34-3.49 µM 之间，比参照物依托泊苷（IC50 为 3.67-13.78 µM）更强。DNA 松弛试验显示，化合物 2 在体外对 Topo IIα 具有很强的抑制活性。对这些化合物的结构-活性关系进行了讨论，表明进一步优化芳基取代的萘类化合物的结构可以发现针对拓扑异构酶的强效抗肿瘤药物。

  DOI：

  10.2174/15734064113096660048

文献信息

• FARNESOID X RECEPTOR AGONISTS
  申请人：Akwabi-Ameyaw Adwoa

  公开号：US20110034507A1

  公开（公告）日：2011-02-10

  The present invention relates to farnesoid X receptors (FXR, NR1H4). FXR is a member of the nuclear receptor class of ligand-activate transcription factors. More particularly, the present invention relates to compounds useful as agonists for FXR, pharmaceutical formulations comprising such compounds, and therapeutic use of the same. Novel isoxazole compounds are disclosed as part of pharmaceutical compositions for the treatment of a condition mediated by decreased FXR activity, such as obesity, diabetes, cholestatic liver disease, liver fibrosis, and metabolic syndrome.

  本发明涉及法尼索德X受体（FXR，NR1H4）。FXR是配体激活转录因子的核受体类成员。更具体地，本发明涉及作为FXR激动剂有用的化合物，包含这些化合物的制药组合物以及其治疗用途。新型异唑咪唑化合物被揭示为用于治疗由FXR活性降低介导的疾病状态的制药组合物，例如肥胖症、糖尿病、胆汁淤积性肝病、肝纤维化和代谢综合征。
• Overcoming Undesirable CYP1A2 Inhibition of Pyridylnaphthalene-Type Aldosterone Synthase Inhibitors: Influence of Heteroaryl Derivatization on Potency and Selectivity
  作者：Ralf Heim、Simon Lucas、Cornelia M. Grombein、Christina Ries、Katarzyna E. Schewe、Matthias Negri、Barbara Birk、Rolf W. Hartmann

  DOI：10.1021/jm800377h

  日期：2008.8.1

  Recently, we reported on the development of potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis. A major drawback of these nonsteroidal compounds was a strong inhibition of the hepatic drug-metabolizing enzyme CYP1A2. In the present study, we examined the influence of substituents in the heterocycle of lead structures with a naphthalene molecular scaffold to overcome this unwanted side effect. With respect to CYP11B2 inhibition, some substituents induced a dramatic increase in inhibitory potency. The methoxyalkyl derivatives 22 and 26 are the most potent CYP11B2 inhibitors up to now (IC50 = 0.2 nM). Most compounds also clearly discriminated between CYP11B2 and CYP11B1, and the CYP1A2 potency significantly decreased in some cases (e.g., isoquinoline derivative 30 displayed only 6% CYP1A2 inhibition at 2 mu M concentration). Furthermore, isoquinoline derivative 28 proved to be capable of passing the gastrointestinal tract and reached the general circulation after peroral administration to male Wistar rats.
• [EN] FARNESOID X RECEPTOR AGONISTS<br/>[FR] AGONISTES DU RÉCEPTEUR DE FARNÉSOÏDE X
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2009005998A1

  公开（公告）日：2009-01-08

  The present invention relates to famesoid X receptors (FXR, NR1H4) FXR is a member of the nuclear receptor class of ligand-activate transcription factors More particularly, the present invention relates to compounds useful as agonists for FXR, pharmaceutical formulations comprising such compounds, and therapeutic use of the same Novel isoxazole compounds are disclosed as part of pharmaceutical compositions for the treatment of a condition mediated by decreased FXR activity, such as obesity, diabetes, cholestatic liver disease, liver fibrosis, and metabolic syndrome

  本发明涉及法内索德X受体（FXR，NR1H4）。FXR是配体激活的转录因子核受体类的一个成员。更具体地说，本发明涉及作为FXR激动剂的化合物，包含该化合物的药物制剂，以及同一治疗用途。新颖的异恶唑化合物被披露作为药物组合物的一部分，用于治疗由FXR活性降低介导的状况，如肥胖、糖尿病、胆汁淤积性肝病、肝纤维化和代谢综合征。
• Synthesis of Aryl-Substituted Naphthalenoids as Potent Topoisomerase Inhibitors
  作者：Yan Shen、Wang Chen、Zhenyu Li、Yuemao Shen

  DOI：10.2174/15734064113096660048

  日期：2014.5.31

  Twelve new aryl-substituted naphthalenoids (1-7, 9, 10, and 13-16) together with four known ones (8, and 11- 13) have been designed and synthesized. Their antitumor activities were evaluated by sulforhodamine B assay on human breast cancer MDA-MB-231, human lung cancer A549 and human cervical cancer HeLa cell lines. Four compounds (2, 4, 10 and 12) showed potent inhibitory activities against the growth of the three cell lines with IC50 between 0.34-3.49 µM, and were more potent than the reference etoposide (IC50 3.67-13.78 µM). DNA relaxation assay revealed that compound 2 showed potent inhibitory activity against Topo IIα in vitro. The structure-activity relationships of these compounds were discussed, suggesting that further structural optimizations of aryl-substituted naphthalenoids could lead to the discovery of potent antitumor agents targeting topoisomerases.

  我们设计并合成了十二种新的芳基取代萘类化合物（1-7、9、10 和 13-16）以及四种已知的萘类化合物（8 和 11-13）。在人乳腺癌 MDA-MB-231、人肺癌 A549 和人宫颈癌 HeLa 细胞系上，通过磺基罗丹明 B 检测法评估了这些化合物的抗肿瘤活性。四种化合物（2、4、10 和 12）对这三种细胞株的生长都有很强的抑制作用，IC50 在 0.34-3.49 µM 之间，比参照物依托泊苷（IC50 为 3.67-13.78 µM）更强。DNA 松弛试验显示，化合物 2 在体外对 Topo IIα 具有很强的抑制活性。对这些化合物的结构-活性关系进行了讨论，表明进一步优化芳基取代的萘类化合物的结构可以发现针对拓扑异构酶的强效抗肿瘤药物。