8-((6-chloropyrimidin-4-yl)oxy)quinoline | 862270-52-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 8-((6-chloropyrimidin-4-yl)oxy)quinoline
• 英文别名: 8-(6-Chloropyrimidin-4-yl)oxyquinoline
• CAS: 862270-52-8
• 化学式: C₁₃H₈ClN₃O
• mdl: MFCD13329183
• 分子量: 257.679
• InChiKey: JZDRSPLWHABZOI-UHFFFAOYSA-N

物化性质

• 沸点：
  431.5±35.0 °C(Predicted)
• 密度：
  1.387±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  羟甲香豆素 、 8-((6-chloropyrimidin-4-yl)oxy)quinoline 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以69%的产率得到4-methyl-7-((6-(quinolin-8-yloxy)pyrimidin-4-yl)oxy)-2H-chromen-2-one
  参考文献：
  名称：

  嘧啶衍生物作为人CAMKIV的潜在抑制剂的设计，合成和生物学评估。

  摘要：

  钙/钙调蛋白依赖性蛋白激酶IV（CAMKIV）是一种多功能Ser / Thr激酶，与脑缺氧，癌症和神经退行性疾病有关。在这里，我们报告七种嘧啶取代的CAMKIV新型抑制剂的设计，合成和生物学评估。我们成功地合成了7种化合物，并对其进行了广泛的表征（ESI-MS，1 H NMR和13 C NMR研究），这些化合物显示出与CAMKIV相当的结合亲和力。分子对接和荧光结合研究表明，化合物1与CAMKIV的结合自由能非常高（DeltaG = -11.52 kcal / mol），结合亲和力（K = 9.2 x 1010 M-1）。我们进一步进行了MTT分析，以检查这些化合物的细胞毒性和抗癌活性。在人肝癌细胞系上观察到化合物1的IC50（39μM）值可观，直到在人胚肾细胞上达到400μM时才无毒。为了确保所有这些化合物的抗癌活性，我们进一步进行了丙二酰亚胺测定，以评估细胞周期中的细胞活力和DNA含量

  DOI：

  10.1111/cbdd.12898
• 作为产物：
  描述：

  4,6-二氯嘧啶 、 8-羟基喹啉 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以81%的产率得到8-((6-chloropyrimidin-4-yl)oxy)quinoline
  参考文献：
  名称：

  嘧啶衍生物作为人CAMKIV的潜在抑制剂的设计，合成和生物学评估。

  摘要：

  钙/钙调蛋白依赖性蛋白激酶IV（CAMKIV）是一种多功能Ser / Thr激酶，与脑缺氧，癌症和神经退行性疾病有关。在这里，我们报告七种嘧啶取代的CAMKIV新型抑制剂的设计，合成和生物学评估。我们成功地合成了7种化合物，并对其进行了广泛的表征（ESI-MS，1 H NMR和13 C NMR研究），这些化合物显示出与CAMKIV相当的结合亲和力。分子对接和荧光结合研究表明，化合物1与CAMKIV的结合自由能非常高（DeltaG = -11.52 kcal / mol），结合亲和力（K = 9.2 x 1010 M-1）。我们进一步进行了MTT分析，以检查这些化合物的细胞毒性和抗癌活性。在人肝癌细胞系上观察到化合物1的IC50（39μM）值可观，直到在人胚肾细胞上达到400μM时才无毒。为了确保所有这些化合物的抗癌活性，我们进一步进行了丙二酰亚胺测定，以评估细胞周期中的细胞活力和DNA含量

  DOI：

  10.1111/cbdd.12898

文献信息

• Vanilloid receptor ligands and their use in treatments
  申请人：Wang Hui-Ling

  公开号：US20050176726A1

  公开（公告）日：2005-08-11

  Pyrimidine ethers and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  嘌呤醚及含有它们的组合物，用于治疗急性、炎症性和神经痛、牙痛、普通头痛、偏头痛、集群头痛、混合血管和非血管综合症、紧张性头痛、一般炎症、关节炎、风湿病、骨关节炎、炎症性肠道疾病、炎症性眼部疾病、炎症性或不稳定的膀胱疾病、牛皮癣、伴有炎症成分的皮肤问题、慢性炎症症状、炎症性疼痛及相关的过敏性疼痛和触痛、神经痛及相关的过敏性疼痛和触痛、糖尿病性神经病痛、烧灼性疼痛、交感神经维持性疼痛、感觉缺失综合症、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿生殖、胃肠或血管区域内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道紊乱、胃溃疡、十二指肠溃疡、腹泻、由坏死剂引起的胃损伤、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。
• [EN] PYRIMIDINE DERIVATIVES FOR USE AS VANILLOID RECEPTOR LIGANDS AND THEIR USE IN THE TREATMENT OF PAIN<br/>[FR] DERIVES DE PYRIMIDINE UTILISES COMME LIGANDS DE RECEPTEUR DE VANILLOIDE ET LEUR UTILISATION DANS LE TRAITEMENT DE LA DOULEUR
  申请人：AMGEN INC

  公开号：WO2005077944A1

  公开（公告）日：2005-08-25

  Pyrimidine ethers and compositions containing them, fo use as vanilloid receptor ligands for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders. Wherein R1 - R4 and X are as defined in the claims.

  含有嘧啶醚化合物的组合物，用作vanilloid受体配体，用于治疗急性、炎症性和神经病理性疼痛、牙痛、普通头痛、偏头痛、群集性头痛、混合血管和非血管综合症、紧张性头痛、一般炎症、关节炎、风湿病、骨关节炎、炎症性肠病、炎症性眼病、炎症性或不稳定膀胱疾病、牛皮癣、具有炎症成分的皮肤疾病、慢性炎症状态、炎症性疼痛及相关的高敏性和触痛、神经病理性疼痛及相关的高敏性和触痛、糖尿病性神经病疼痛、交感神经维持的疼痛、去神经症候群、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿、胃肠或血管区域内脏运动障碍、创伤、烧伤、过敏性皮肤反应、瘙痒、白癜风、一般胃肠道疾病、胃溃疡、十二指肠溃疡、腹泻、坏死性剂引起的胃病变、毛发生长、血管运动性或过敏性鼻炎、支气管疾病或膀胱疾病。其中R1-R4和X的定义如权利要求中所述。
• Structure guided design of potential inhibitors of human calcium–calmodulin dependent protein kinase IV containing pyrimidine scaffold
  作者：Huma Naz、Ehtesham Jameel、Nasimul Hoda、Ashutosh Shandilya、Parvez Khan、Asimul Islam、Faizan Ahmad、B. Jayaram、Md. Imtaiyaz Hassan

  DOI：10.1016/j.bmcl.2015.12.098

  日期：2016.2

  Calmodulin dependent protein kinase IV (CAMKIV) belongs to the serine/threonine protein kinase family and considered as an encouraging target for the development of novel anticancer agents. The interaction and binding behavior of three designed inhibitors of human CAMKIV, containing pyrimidine scaffold, was monitored by in vitro fluorescence titration and molecular docking calculations under physiological condition. In silico docking studies were performed to screen several compounds containing pyrimidine scaffold against CAMKIV. Molecular docking calculation predicted the binding of these ligands in active-site cavity of the CAMKIV structure correlating such interactions with a probable inhibition mechanism. Finally, three active pyrimidine substituted compounds (molecules 1-3) have been successfully synthesized and characterized by H-1 and C-13 NMR. Molecule 3 is showing very high binding-affinity for the CAMKIV, with a binding constant of 2.2 X 10(8), M-1 (+/- 0.20). All three compounds are nontoxic to HEK293 cells up to 50 mu M. The cell proliferation inhibition study showed that the molecule 3 has lowest IC50 value (46 +/- 1.08 mu M). The theoretical and experimental observations are significantly correlated. This study reveals some important observations to generate an improved pyrimidine based compound that holds promise as a therapeutic agent for the treatment of cancer and neurodegenerative diseases. (C) 2015 Elsevier Ltd. All rights reserved.
• PYRIMIDINE DERIVATIVES FOR USE AS VANILLOID RECEPTOR LIGANDS AND THEIR USE IN THE TREATMENT OF PAIN
  申请人：AMGEN INC.

  公开号：EP1720868A1

  公开（公告）日：2006-11-15
• US7511044B2
  申请人：——

  公开号：US7511044B2

  公开（公告）日：2009-03-31