2,5-dichloro-N-phenethylpyrimidin-4-amine | 1531285-95-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2,5-dichloro-N-phenethylpyrimidin-4-amine
• 英文别名: 2,5-dichloro-N-(2-phenylethyl)pyrimidin-4-amine
• CAS: 1531285-95-6
• 化学式: C₁₂H₁₁Cl₂N₃
• 分子量: 268.145
• InChiKey: IQNCNQSDFUEBBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,5-dichloro-N-phenethylpyrimidin-4-amine 在 ether hydrochloride 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  作为有效抗结核药的新型嘧啶衍生物的设计与合成

  摘要：

  各种耐药结核分枝杆菌（Mtb）菌株的出现，需要探索与现有疗法缺乏交叉耐药性的新药。通过筛选MedChemExpress生物活性化合物库，赛立替尼被鉴定为对Mtb H37Ra具有活性的化合物。赛瑞替尼在体外的MIC值为9.0μM ，并在感染自体发光H37Ra的BALB / c小鼠模型中证明了体内功效。然后，合成了32种新的ceritinib衍生物，并在体外评估了它们的抗分枝杆菌活性。。合成的化合物的抗分枝杆菌活性受嘧啶核第4位的取代影响很大，而由于嘧啶第2位的2-异丙氧基-5-甲基-4-（哌啶丁-4-基）苯胺的存在增强了合成化合物的抗分枝杆菌活性。核。在体内的三个最有效的化合物的抗结核活性进行了评价。5-氯-N 2-（2-异丙氧基-5-甲基-4-（哌啶-4-基）苯基）-N 4-（萘他伦-1-基）嘧啶-2,4-二胺（16j）减轻了小鼠的Mtb负担。该结果表明16j作为具有优异抗结核活性的新药的

  DOI：

  10.1016/j.ejmech.2018.11.054
• 作为产物：
  描述：

  2,4,5-三氯嘧啶 、 2-苯乙胺 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 3.0h， 以74.6%的产率得到2,5-dichloro-N-phenethylpyrimidin-4-amine
  参考文献：
  名称：

  作为有效抗结核药的新型嘧啶衍生物的设计与合成

  摘要：

  各种耐药结核分枝杆菌（Mtb）菌株的出现，需要探索与现有疗法缺乏交叉耐药性的新药。通过筛选MedChemExpress生物活性化合物库，赛立替尼被鉴定为对Mtb H37Ra具有活性的化合物。赛瑞替尼在体外的MIC值为9.0μM ，并在感染自体发光H37Ra的BALB / c小鼠模型中证明了体内功效。然后，合成了32种新的ceritinib衍生物，并在体外评估了它们的抗分枝杆菌活性。。合成的化合物的抗分枝杆菌活性受嘧啶核第4位的取代影响很大，而由于嘧啶第2位的2-异丙氧基-5-甲基-4-（哌啶丁-4-基）苯胺的存在增强了合成化合物的抗分枝杆菌活性。核。在体内的三个最有效的化合物的抗结核活性进行了评价。5-氯-N 2-（2-异丙氧基-5-甲基-4-（哌啶-4-基）苯基）-N 4-（萘他伦-1-基）嘧啶-2,4-二胺（16j）减轻了小鼠的Mtb负担。该结果表明16j作为具有优异抗结核活性的新药的

  DOI：

  10.1016/j.ejmech.2018.11.054

文献信息

• MULTI-SUBSTITUTED PYRIMIDINE DERIVATIVES WITH EXCELLENT KINASE INHIBITORY ACTIVITIES
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US20190315726A1

  公开（公告）日：2019-10-17

  Disclosed are a novel pyrimidine derivative compound, a pharmaceutically acceptable salt thereof, a method for preparing the compound and a pharmaceutical use of the compound as an anticancer agent or a therapeutic agent for degenerative brain diseases. Specifically, the novel pyrimidine derivative compound has excellent inhibitory activities against kinase enzymes such as ARK5/NUAK1, ACK1, FLT3, JAK1, JAK2 and JAK2 (V617F) and thus is useful for treating and preventing leukemia, ovarian cancer, breast cancer, non-small cell carcinoma, colorectal cancer, glioma, and brain protein abnormalities such as Alzheimer's disease, progressive supranuclear palsy and frontotemporal dementia, that is, degenerative diseases caused by Tau deposition.

  本文披露了一种新型嘧啶衍生物化合物，其药用盐，制备该化合物的方法以及将该化合物用作抗癌剂或治疗退行性脑疾病的药用。具体来说，这种新型嘧啶衍生物化合物对激酶酶类如ARK5/NUAK1、ACK1、FLT3、JAK1、JAK2和JAK2(V617F)具有出色的抑制活性，因此可用于治疗和预防白血病、卵巢癌、乳腺癌、非小细胞癌、结直肠癌、胶质瘤以及脑蛋白异常疾病，如阿尔茨海默病、进行性核上性麻痹和颞叶痴呆等由Tau沉积引起的退行性疾病。
• [EN] INHIBITORS OF ACK1/TNK2 TYROSINE KINASE<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE ACK1/TNK2
  申请人：H LEE MOFFITT CANCER CENTER & RES INST

  公开号：WO2017023899A1

  公开（公告）日：2017-02-09

  Described are cancer therapies and anti-cancer compounds. In particular, disclosed are ihibitors of ACK1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new ACK1 tyrosine kinase inhibitors are also disclosed. In specifc example, compound having Formula I are disclosed.

  本文描述了癌症治疗和抗癌化合物。特别地，本文披露了ACK1酪氨酸激酶抑制剂及其在癌症治疗中的应用。本文还披露了筛选新的ACK1酪氨酸激酶抑制剂的方法。在具体的例子中，披露了具有I式的化合物。
• Inhibitors of ACK1/TNK2 tyrosine kinase
  申请人：H. LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE, INC.

  公开号：US10336734B2

  公开（公告）日：2019-07-02

  Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of ACK1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new ACK1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I are disclosed.

  所述的是癌症疗法和抗癌化合物。特别是，公开了 ACK1 酪氨酸激酶的抑制剂及其在治疗癌症中的用途。还公开了筛选新的 ACK1 酪氨酸激酶抑制剂的方法。在具体实例中，公开了具有式I的化合物。
• Multi-substituted pyrimidine derivatives with excellent kinase inhibitory activities
  申请人：KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY

  公开号：US10683282B2

  公开（公告）日：2020-06-16

  Disclosed are a novel pyrimidine derivative compound, a pharmaceutically acceptable salt thereof, a method for preparing the compound and a pharmaceutical use of the compound as an anticancer agent or a therapeutic agent for degenerative brain diseases. Specifically, the novel pyrimidine derivative compound has excellent inhibitory activities against kinase enzymes such as ARK5/NUAK1, ACK1, FLT3, JAK1, JAK2 and JAK2 (V617F) and thus is useful for treating and preventing leukemia, ovarian cancer, breast cancer, non-small cell carcinoma, colorectal cancer, glioma, and brain protein abnormalities such as Alzheimer's disease, progressive supranuclear palsy and frontotemporal dementia, that is, degenerative diseases caused by Tau deposition.

  本发明公开了一种新型嘧啶衍生物化合物、其药学上可接受的盐、制备该化合物的方法以及该化合物作为抗癌剂或退行性脑疾病治疗剂的药物用途。具体地说，该新型嘧啶衍生物化合物对激酶如 ARK5/NUAK1、ACK1、FLT3、JAK1、JAK2 和 JAK2 (V617F)具有极好的抑制活性，因此可用于治疗和预防白血病、卵巢癌、乳腺癌、非小细胞癌、乳腺癌、非小细胞肺癌、非小细胞肺癌、非小细胞肺癌、非小细胞肺癌、非小细胞肺癌、非小细胞肺癌和非小细胞肺癌、乳腺癌、非小细胞癌、结直肠癌、胶质瘤，以及阿尔茨海默病、进行性核上性麻痹和额颞叶痴呆等脑蛋白异常，即由 Tau 沉积引起的退行性疾病。
• Discovery and SARs of 5-Chloro-<i>N</i>⁴-phenyl-<i>N</i>²-(pyridin-2-yl)pyrimidine-2,4-diamine Derivatives as Oral Available and Dual CDK 6 and 9 Inhibitors with Potent Antitumor Activity
  作者：Yang Wang、Xing Chen、Yaoyao Yan、Xiaochen Zhu、Mingming Liu、Xinhua Liu

  DOI：10.1021/acs.jmedchem.9b02121

  日期：2020.3.26

  Cyclin-dependent kinases (CDKs) are promising therapeutic targets for cancer therapy. Herein, we describe our efforts toward the discovery of a series of 5-chloro-N-4-phenyl-N-2(pyridin-2-yl)pyrimidine-2,4-diamine derivatives as dual CDK6 and 9 inhibitors. Intensive structural modifications lead to the identification of compound 66 as the most active dual CDK6/9 inhibitor with balancing potency against these two targets and good selectivity over CDK2. Further biological studies revealed that compound 66 was directly bound to CDK6/9, resulting in suppression of their downstream signaling pathway and inhibition of cell proliferation by blocking cell cycle progression and inducing cellular apoptosis. More importantly, compound 66 significantly inhibited tumor growth in a xenograft mouse model with no obvious toxicity, indicating the promising therapeutic potential of CDK6/9 dual inhibitors for cancer treatment. Therefore, the above results are of great importance in the development of dual CDK6/9 inhibitors for cancer therapy.