5-(cyclohexylmethoxy)-4-oxo-4H-chromene-3-carbaldehyde | 1229444-25-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 5-(cyclohexylmethoxy)-4-oxo-4H-chromene-3-carbaldehyde
• 英文别名: 5-(Cyclohexylmethoxy)-4-oxochromene-3-carbaldehyde
• CAS: 1229444-25-0
• 化学式: C₁₇H₁₈O₄
• 分子量: 286.328
• InChiKey: JTEVQKPRVBJVKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(cyclohexylmethoxy)-4-oxo-4H-chromene-3-carbaldehyde 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.17h， 生成 5-(cyclohexylmethoxy)-3-((2-hydroxyethylamino)-methyl)-4H-chromen-4-one
  参考文献：
  名称：

  N-酰基羟乙基氨基甲基-4 H - chromen-4 -one支架的新型类似物作为IL-5抑制剂

  摘要：

  制备了许多N-酰基取代的羟乙基氨基甲基-4 H-铬基-4-酮6a – u并评估了其对IL-5的抑制活性。其中，化合物6r（在30 µM时抑制率为95.0％，IC 50  = 10.0 µM，C log P = 4.1549）显示出最有效的抑制活性。结构活性关系表明，尿素，氨基甲酸酯或酰胺基团上较大或疏水的取代基对IL-5具有良好的抑制活性。此外，苯环上的给电子基团（6g和6s）比吸电子基团（6f）更具活性）。最后，用大的脂族取代基取代环A第5位的环己基甲氧基导致活性丧失。

  DOI：

  10.1016/j.bmc.2017.06.018
• 作为产物：
  描述：

  2,6-二羟基苯乙酮 在 potassium carbonate 、 三氯氧磷 作用下， 以 丙酮 为溶剂， 生成 5-(cyclohexylmethoxy)-4-oxo-4H-chromene-3-carbaldehyde
  参考文献：
  名称：

  N-酰基羟乙基氨基甲基-4 H - chromen-4 -one支架的新型类似物作为IL-5抑制剂

  摘要：

  制备了许多N-酰基取代的羟乙基氨基甲基-4 H-铬基-4-酮6a – u并评估了其对IL-5的抑制活性。其中，化合物6r（在30 µM时抑制率为95.0％，IC 50  = 10.0 µM，C log P = 4.1549）显示出最有效的抑制活性。结构活性关系表明，尿素，氨基甲酸酯或酰胺基团上较大或疏水的取代基对IL-5具有良好的抑制活性。此外，苯环上的给电子基团（6g和6s）比吸电子基团（6f）更具活性）。最后，用大的脂族取代基取代环A第5位的环己基甲氧基导致活性丧失。

  DOI：

  10.1016/j.bmc.2017.06.018

文献信息

• 인터루킨-5 저해효과를 갖는 신규 하이드록시에틸아미노메틸크로메논 유도체
  申请人：The Industry & Academic Cooperation in Chungnam National University (IAC) 충남대학교산학협력단(220040084104) BRN ▼314-82-09264

  公开号：KR101535119B1

  公开（公告）日：2015-07-09

  본 발명은 신규 하이드록시에틸아미노메틸크로메논 유도체, 이의 제조방법, 또는 상기 하이드록시에틸아미노메틸크로메논 유도체를 함유하는 알레르기 질환의 예방 또는 치료용 약학 조성물에 관한 것이다. 상기 하이드록시에틸아미노메틸크로메논 유도체는 저분자의 비펩타이드 계열 물질이기에, 종래 알려진 알르레기 질환의 치료제와는 달리 단백질에 대한 비특이적 반응이 없다. 또한, 본 발명의 하이드록시에틸아미노메틸크로메논 유도체는 아민 형태의 화합물로서 종래에 제조되어 있던 하이드록시에틸아미노메틸크로메논 유도체와 비교하였을 때 수용성이 크게 증가하였을 뿐만 아니라, 화학적 구조의 상이함으로 인해, 인터루킨-5의 저해효과가 더 높기에, 본 발명의 화합물은 알르레기 질환의 억제제로 유용하게 활용될 수 있다. 게다가, 기존의 하이드록시에틸아미노메틸크로메논 유도체에는 비대칭 중심(chiral center)이 있어, 화합물 제조시 이성체의 유무 등을 확인해야 하는 번거로움이 있으나, 본 발명에서는 이와 같은 문제가 해결되어 화합물을 용이하게 제조할 수 있다는 장점이 있다.

  本发明涉及一种新的羟乙基氨甲基克罗酮衍生物，其制备方法，或者含有所述羟乙基氨甲基克罗酮衍生物的用于预防或治疗过敏性疾病的药学组合物。所述羟乙基氨甲基克罗酮衍生物是低分子肽类物质，因此与传统已知的过敏性疾病治疗药物不同，不会引起对蛋白质的非特异性反应。此外，本发明的羟乙基氨甲基克罗酮衍生物是氨基化合物，与传统制备的羟乙基氨甲基克罗酮衍生物相比，其溶解性显著增加，且由于化学结构的不同，其对白细胞介素-5的抑制效果更强，因此本发明的化合物可用作过敏性疾病的抑制剂。此外，传统的羟乙基氨甲基克罗酮衍生物具有不对称中心，因此在化合物制备过程中需要确认异构体的存在等，而本发明解决了这一问题，使得化合物的制备更加容易。
• Synthesis and evaluation of novel chromone analogs for their inhibitory activity against interleukin-5
  作者：Pillaiyar Thanigaimalai、Tuan Anh Le Hoang、Ki-Cheul Lee、Vinay K. Sharma、Seong-Cheol Bang、Jun Ho Yun、Eunmiri Roh、Youngsoo Kim、Sang-Hun Jung

  DOI：10.1016/j.ejmech.2010.02.041

  日期：2010.6

  A novel series of chromone analogs were synthesized and evaluated for their inhibitory activity against interleukin-5. Among them compounds 5-Cyclohexylmethoxy-3-(4-hydroxybenzyl)-4H-chromen-4-one (6a, 98% inhibition at 30 μM, IC50 < 3.0 μM) and 5-Cyclohyxylmethoxy-3-(hydroxymethyl)-4H-chromen-4-one (8a, 84% inhibition at 30 μM, IC50 = 7.6 μM) showed most potent activity. The structural requirement

  合成了一系列新的色酮类似物，并评估了其对白介素5的抑制活性。其中化合物5-环己基甲氧基-3-（4-羟基苄基）-4 H- 铬-4--4-酮（6a，在30μM时抑制率为98％，IC 50 <3.0μM）和5-环己基甲氧基-3-（羟甲基）- 4 H -chromen-4-one（8a，30μM时抑制84％，IC 50 = 7.6μM）表现出最强的活性。具有抑制IL-5抑制活性的色酮类似物的结构要求可以概括为：（i）疏水基团（在环A的第5位的环己基甲氧基）的重要性，（ii）具有较小氢键基团的环B的要求具有给电子性，例如在第4位的酚羟基和（iii）1-4n铬烯环的平面性。
• Identification of novel chromenone derivatives as interleukin-5 inhibitors
  作者：Eeda Venkateswararao、Min-Seok Kim、Vinay K. Sharma、Ki-Cheul Lee、Santhosh Subramanian、Eunmiri Roh、Youngsoo Kim、Sang-Hun Jung

  DOI：10.1016/j.ejmech.2012.11.007

  日期：2013.1

  A series of (E)-5-alkoxy-3-(3-phenyl-3-oxoprop-1-enyl)-4H-chromen-4-ones (4) and (E)-5-alkoxy-3-(3-hydroxy-3-phenylprop-1-enyl)-4H-chromen-4-ones (5) were synthesized and evaluated for their IL-5 inhibitory activity. Propenone analogs 4 possess some of the structurally important characteristics of isoflavone 2 and chalcone 3 previously known as potent IL-5 inhibitor. However, the inhibitory activity of 4 was weak and therefore this structural hybridization appears to be ineffective for the design of IL-5 inhibitor. Meanwhile the potent activity profile of compounds 5 was discovered. This enhanced activity of 5 compared to 4 could be due to the effective location of hydroxyl group of allylic alcohol moiety of 5 in the 3D structure. The electron withdrawing substituents at position 4 of phenyl ring of 5 enhances the activity possibly due to an increase in the strength of hydrogen bonding property of hydroxyl group of allylic alcohol moiety. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Design and synthesis of novel hydroxyalkylaminomethylchromones for their IL-5 inhibitory activity
  作者：P. Thanigaimalai、Ki-Cheul Lee、Vinay K. Sharma、Jun-Ho Yun、Youngsoo Kim、Sang-Hun Jung

  DOI：10.1016/j.bmc.2010.05.028

  日期：2010.7

  A series of hydroxyalkylaminomethylchromone analogs 3 were prepared and evaluated as inhibitors of interleukin-5. The most active analog 3d inhibited interleukin-5 activity with an IC50 of 17.5 mu M. The structural requirements of chromone analogs possessing the inhibitory activity against IL-5 could be summarized as: (i) the cyclohexylmethoxy group at 5th position of the A ring, (ii) the planarity of chromone ring, (iii) hydrophobic unit around the B ring with hydroxyl functional group, (iv) the hydrophobic unit which does not have to be a planar and ( v) the length of carbon units between amino and hydroxyl group is limited to two. (C) 2010 Elsevier Ltd. All rights reserved.
• Novel interleukin-5 inhibitors based on hydroxyethylaminomethyl-4H-chromen-4-one scaffold
  作者：Cheonik Joo、Eeda Venkateswararao、Ki-Cheul Lee、Vinay K. Sharma、Min-Sik Kyung、Youngsoo Kim、Sang-Hun Jung

  DOI：10.1016/j.bmc.2012.08.006

  日期：2012.10

  Hydroxyethylaminomethyl-4H-chromenones were previously discovered as fairly strong IL-5 inhibitor. For determination of detail structure activity relationship, N-substituted hydroxyethylaminomethyl-chromenones 4a-n were prepared and evaluated for their IL-5 inhibitory activity. Shifting the hydrophobic group to nitrogen from 1-position of hydroxyethylamino moiety of hydroxyethylaminomethyl-4H-chromenones enhances the activity. The increment in bulkiness or hydrophobicity of alkyl side chain at amino group increases the activity. The same level of activity of 5-(cyclohexylmethoxy)-3-(N-benzyl-2-hydroxyethylaminomethyl)-4H-chromenone analogs regardless of hydrophobic or hydrophilic substituents at 4th position of phenyl ring might infer the existence of tunnel structure in the putative receptor for accepting these side chains. (C) 2012 Elsevier Ltd. All rights reserved.