5-(2-chloropyrimidin-4-yloxy)-1H-indole | 930094-97-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(2-chloropyrimidin-4-yloxy)-1H-indole
• 英文别名: 5-[(2-chloro-4-pyrimidinyl)oxy]-1H-indole；5-(2-chloropyrimidin-4-yl)oxy-1H-indole
• CAS: 930094-97-6
• 化学式: C₁₂H₈ClN₃O
• 分子量: 245.668
• InChiKey: OWBJBDFVKKNCFD-UHFFFAOYSA-N

物化性质

• 沸点：
  490.7±20.0 °C(Predicted)
• 密度：
  1.437±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 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：
  50.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(2-chloropyrimidin-4-yloxy)-1H-indole 、 二碳酸二叔丁酯 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 tert-butyl 5-[(2-chloropyrimidin-4-yl)oxy]-1H-indole-1-carboxylate
  参考文献：
  名称：

  WO2007/35309

  摘要：

  公开号：
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 5-羟基吲哚 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 5-(2-chloropyrimidin-4-yloxy)-1H-indole
  参考文献：
  名称：

  Structure-Activity Relationship of Indole-Tethered Pyrimidine Derivatives that Concurrently Inhibit Epidermal Growth Factor Receptor and Other Angiokinases

  摘要：

  抗血管生成剂已经被广泛研究，以与标准化疗或靶向抗癌药物结合使用，从而更好地管理晚期癌症。那些能够同时抑制表皮生长因子受体和其他血管生成激酶的治疗药物，可能是表皮生长因子受体依赖性癌症的有效替代组合疗法。在这里，我们报告了一种使用生物同位素替代策略合成的吲哚衍生物，这种化合物被命名为MKP101。MKP101不仅抑制了表皮生长因子受体，其IC50值为43 nM，而且同样强效地抑制了血管生成激酶。此外，MKP101有效抑制了由血管内皮生长因子诱导的人脐带静脉内皮细胞的增殖、管状形成、迁移，以及HCC827（一个依赖于表皮生长因子受体的癌细胞系）的增殖。我们生成了MKP101与表皮生长因子受体激酶结构域的对接模型，以预测其结合模式，并通过合成和评估MKP101衍生物进行了验证。此外，对来自MKP101的吲哚氨基或吲哚氧基嘧啶类类似物的结构-活性关系的研究表明，对表皮生长因子受体和其他血管生成激酶，特别是血管内皮生长因子受体2的选择性，依赖于取代基在嘧啶上的位置以及嘧啶与吲哚部分之间的连接类型。我们相信，这项研究为开发具有高亲和力的血管生成激酶抑制剂，基于嘧啶骨架，提供了基础。

  DOI：

  10.1371/journal.pone.0138823

文献信息

• 신규 파조파닙 유도체 및 이를 함유하는 약학조성물
  申请人：CHUNG ANG University industry Academic Cooperation Foundation 중앙대학교 산학협력단(220040385305) BRN ▼108-82-05979

  公开号：KR20160147170A

  公开（公告）日：2016-12-22

  본 발명은 혈관신생 억제 활성 및 상피세포성장인자 억제 활성을 동시에 갖는 신규 파조파닙 유도체 또는 그의 염과, 이를 유효성분으로 함유하는 약학조성물에 관한 것으로서, 상기 파조파닙 유도체는 파조파닙과 달리 혈관신생 억제 활성 외 상피세포성장인자를 억제하는 활성을 동시에 갖고 있어 다표적 타겟을 통해 보다 효과적으로 폐암, 결장암 또는 유방암과 같은 EGFR 관련 암질환을 치료하고 예방할 수 있으며 특히 이레사나 타세바가 효과를 발휘하지 못하는 비소세포성 폐암을 효과적으로 치료하고 예방할 수 있다.

  本发明涉及一种具有血管新生抑制活性和上皮细胞生长因子抑制活性的新型帕约帕尼诱导体或其盐，以及包含其作为有效成分的药学组合物，所述帕约帕尼诱导体与帕约帕尼不同，同时具有抑制血管新生活性和上皮细胞生长因子的活性，可通过多种靶点更有效地治疗和预防EGFR相关癌症，如肺癌、结肠癌或乳腺癌，特别是对于厄洛替尼或塔塞瑞不能发挥作用的非小细胞肺癌，可以有效地进行治疗和预防。
• Cyclic Diaryl Ureas Suitable as Tyrosine Kinase Inhibitors
  申请人：Bold Guido

  公开号：US20080039440A1

  公开（公告）日：2008-02-14

  The invention relates to novel compounds of Formula I: wherein p is 1, 2 or 3; n is 0, 1, 2 or 3; m is 0, 1, 2 or 3; A is CR c , S, NR c or O, where R c is H or lower alkyl; X, Y and Z are each independently selected from N or C—R 3 , wherein at least two of X, Y and Z are N; and each R a is independently selected from hydrogen and lower-alkyl; each R b is hydrogen or lower-alkyl; G is a group Ar or represents CN or unsubstituted or substituted lower alkyl; Ar is a saturated or unsaturated cyclic group, which is substituted or unsubstituted and maybe a five or six membered monocyclic or a 8, 9, 10, 11 or 12 membered bicyclic or tricyclic ring and may contain 0, 1, 2 or 3 heteroatoms selected from O, N and S; and wherein the radicals have R 1 , R 2 , R 3 and R 4 have the meanings as defined herein, to salts, esters, N-oxides or prodrugs thereof; and their use in the treatment of protein kinase dependent diseases, their use in the manufacture of pharmaceutical compositions for use in the treatment of said diseases, methods of use of diary urea derivatives in the treatment of said diseases, pharmaceutical preparations comprising these novel diaryl urea derivatives, processes for the manufacture of the novel diaryl urea derivatives, the use or methods of use of the novel diaryl urea derivatives as mentioned above, and/or these novel diaryl urea derivatives for use in the treatment of the animal or human body.

  本发明涉及公式I的新化合物：其中p为1、2或3；n为0、1、2或3；m为0、1、2或3；A为CRc、S、NRcor O，其中Rcis H或较低的烷基；X、Y和Z各自独立地选择自N或C—R3，其中至少有两个X、Y和Z为N；而每个Rais独立选择自氢和较低的烷基；每个Rbis氢或较低的烷基；G是Ar基团或表示CN或未取代或取代的较低烷基；Ar是饱和或不饱和的环状基团，其被取代或未取代，并且可能是五元或六元的单环或8、9、10、11或12元的双环或三环，并且可能包含0、1、2或3个从O、N和S中选择的杂原子；其中基团具有R1、R2、R3和R4的含义如本文所定义，其盐、酯、N-氧化物或前药；并且它们在蛋白激酶依赖性疾病的治疗中的使用，它们在制造用于治疗该等疾病的药物组合物中的使用，二苯基脲衍生物在治疗该等疾病中的使用方法，包括这些新的二苯基脲衍生物的制药制剂，制造新的二苯基脲衍生物的方法，上述提到的新的二苯基脲衍生物的使用或使用方法，以及/或这些新的二苯基脲衍生物用于治疗动物或人体。
• Cyclic diaryl ureas suitable as tyrosine kinase inhibitors
  申请人：Novartis AG

  公开号：US07855215B2

  公开（公告）日：2010-12-21

  The invention relates to novel compounds of Formula I: wherein p is 1, 2 or 3; n is 0, 1, 2 or 3; m is 0, 1, 2 or 3; A is CRc, S, NRc or O, where Rc is H or lower alkyl; X, Y and Z are each independently selected from N or C—R3, wherein at least two of X, Y and Z are N; and each Ra is independently selected from hydrogen and lower-alkyl; each Rb is hydrogen or lower-alkyl; G is a group Ar or represents CN or unsubstituted or substituted lower alkyl; Ar is a saturated or unsaturated cyclic group, which is substituted or unsubstituted and maybe a five or six membered monocyclic or a 8, 9, 10, 11 or 12 membered bicyclic or tricyclic ring and may contain 0, 1, 2 or 3 heteroatoms selected from O, N and S; and wherein the radicals have R1, R2, R3 and R4 have the meanings as defined herein, to salts, esters, N-oxides or prodrugs thereof; and their use in the treatment of protein kinase dependent diseases, their use in the manufacture of pharmaceutical compositions for use in the treatment of said diseases, methods of use of diary urea derivatives in the treatment of said diseases, pharmaceutical preparations comprising these novel diaryl urea derivatives, processes for the manufacture of the novel diaryl urea derivatives, the use or methods of use of the novel diaryl urea derivatives as mentioned above, and/or these novel diaryl urea derivatives for use in the treatment of the animal or human body.

  本发明涉及一种新型化合物，其化学式为I：其中，p为1、2或3；n为0、1、2或3；m为0、1、2或3；A为CRc、S、NRc或O，其中Rc为H或低级烷基；X、Y和Z分别独立地选自N或C—R3，其中至少两个为N；每个Ra独立地选自氢和低级烷基；每个Rb为氢或低级烷基；G为Ar基团或表示CN或未取代或取代的低级烷基；Ar为饱和或不饱和的环状基团，其取代或未取代，可能是五元或六元单环或8、9、10、11或12元的双环或三环，并且可能包含0、1、2或3个来自O、N和S的杂原子；所述基团R1、R2、R3和R4的含义如本文所定义，以及其盐、酯、N-氧化物或前药；以及它们在蛋白激酶依赖性疾病的治疗中的应用，它们在制造用于治疗该疾病的药物组合物中的应用，以及使用二苯基脲衍生物治疗该疾病的方法，包括这些新型二苯基脲衍生物的制药制剂，制造这些新型二苯基脲衍生物的方法，上述新型二苯基脲衍生物的使用或使用方法，和/或这些新型二苯基脲衍生物用于治疗动物或人体的用途。
• HETEROBICYCLIC CARBOXAMIDES AS INHIBITORS FOR KINASES
  申请人：ARTMANN, III Gerald David

  公开号：US20120245187A1

  公开（公告）日：2012-09-27

  The invention relates to novel organic compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising a compound of formula I and to the use of a compound of formula I for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in the treatment of tumour diseases and ocular neovascular diseases.

  本发明涉及一种新型有机化合物(I)及其在动物或人体治疗中的应用，包括含有化合物I的制药组合物以及利用化合物I制备用于治疗蛋白激酶依赖性疾病的制药组合物的应用，特别是在治疗增殖性疾病，如肿瘤疾病和眼部新生血管疾病方面的应用。
• Heterobicyclic Carboxamides as inhibitors for kinases
  申请人：Artmann, III Gerald David

  公开号：US20100168082A1

  公开（公告）日：2010-07-01

  The invention relates to novel organic compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising a compound of formula I and to the use of a compound of formula I for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in the treatment of tumour diseases and ocular neovascular diseases.

  本发明涉及一种新型有机化合物(I)及其在动物或人体治疗中的应用，包括含有化合物I的药物组合物，以及利用化合物I制备用于治疗蛋白激酶依赖性疾病的药物组合物，特别是用于治疗增殖性疾病，如肿瘤疾病和眼部新生血管疾病的治疗。