5-bromo-2-chloro-4-(3-nitrophenoxy)pyrimidine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-bromo-2-chloro-4-(3-nitrophenoxy)pyrimidine
• 英文别名: 5-Bromo-2-chloro-4-(3-nitrophenoxy)pyrimidine
• 化学式: C₁₀H₅BrClN₃O₃
• mdl: MFCD22832671
• 分子量: 330.525
• InChiKey: QJQJHXPUOWZRNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  80.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-bromo-2-chloro-4-(3-nitrophenoxy)pyrimidine 在 platinum(IV) oxide 、 氢气 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 仲丁醇 为溶剂， 生成 N-[3-[5-bromo-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]prop-2-enamide
  参考文献：
  名称：

  Discovery of selective irreversible inhibitors for EGFR-T790M

  摘要：

  Targeting the epidermal growth factor receptor kinase (EGFR) with ATP-competitive kinase inhibitors results in dramatic but short-lived responses in patients with EGFR mutant non small cell lung cancer. A series of novel covalent EGFR kinase inhibitors with selectivity for the clinically relevant T790M 'gatekeeper' resistance mutation relative to wild-type EGFR were discovered by library screening. A representative compound 3i was obtained through a systematic SAR study guided by mutant EGFR-dependent cellular proliferation assays. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.036
• 作为产物：
  描述：

  5-溴-2,4-二氯嘧啶 、 间硝基苯酚 在 sodium hydride 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以93%的产率得到5-bromo-2-chloro-4-(3-nitrophenoxy)pyrimidine
  参考文献：
  名称：

  신규한 5-(3,6-디하이드로-2H-피란-4-일)-4-치환-N-(1-치환-1H-피라졸-4-일)(N-헤테로아릴)-2-아민 유도체 및 이의 용도

  摘要：

  本发明涉及一种新的5-(3,6-二氢-2H-吡喃-4-基)-4-取代-N-(1-取代-1H-吡唑-4-基)(N-杂环芳基)-2-胺衍生物化合物或其药学上可接受的盐，包含其作为有效成分的用于预防或治疗JAK3相关疾病的药学组合物，以及所述药学组合物用于预防或治疗JAK3相关疾病的方法。

  公开号：

  KR20200137088A

文献信息

• [EN] PYRIMIDINE COMPOUNDS, COMPOSITIONS, AND MEDICINAL APPLICATIONS THEREOF<br/>[FR] COMPOSÉS DE PYRIMIDINE, COMPOSITIONS ET LEURS APPLICATIONS MÉDICALES
  申请人：LENGO THERAPEUTICS INC

  公开号：WO2022094354A1

  公开（公告）日：2022-05-05

  The present disclosure relates to a class of pyrimidine compounds, their stereoisomers, tautomers, pharmaceutically acceptable salts, stereoisomers, solvates, and hydrates thereof. The present disclosure also relates to a process of preparation of these pyrimidine compounds, pharmaceutical compositions containing them, and medicinal applications thereof.

  本公开涉及一类嘧啶化合物及其立体异构体、互变异构体、药学上可接受的盐、立体异构体、溶剂化物和水合物。本公开还涉及制备这些嘧啶化合物的方法、含有它们的药物组合物以及它们的医药应用。
• Discovery of 5-bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives as novel ULK1 inhibitors that block autophagy and induce apoptosis in non-small cell lung cancer
  作者：Dejuan Sun、Zijian Yang、Yongqi Zhen、Yushang Yang、Yanmei Chen、Yong Yuan、Lan Zhang、Xiaoxi Zeng、Lixia Chen

  DOI：10.1016/j.ejmech.2020.112782

  日期：2020.12

  UNC51-like kinase1 (ULK1) recruits its binding partners and initiates the autophagy process in cancer. ULK1 is significantly overexpressed in Non-small cell lung cancer (NSCLC) and negatively correlated with clinical prognosis in NSCLC patients. Based upon the binding features of ULK1, we explored the pharmacophore modeling to discover the common anchoring features. It was verified by synthesizing 5-bromo-4-phenoxy-N-phenylpyrimidin-2-amine derivatives, as well as subsequently elucidating the structure-activity relationships (SAR). Among all the obtained ULK1 inhibitors, 5-bromo-4-(2-fluoro-4-nitrophenoxy)-N-(3,4,5-trimethoxyphenyl) pyrimidin-2-amine (3s), was the most active one. The docking analysis was conducted to compare 3s and SBI-0206965, which further elucidated the roles of the H-bond donor. This compound inhibited the proliferation of A549 cells and showed strong inhibitory activity against ULK1 kinase. Moreover, we found that compound 3s could induce apoptosis while simultaneously blocking autophagy. Collectively, these findings shed new light on compound 3s that would be utilized as a promising candidate drug for the future NSCLC therapy.
• [EN] 2, 4, 5-SUBSTITUTED PYRIMIDINE DERIVATIVE, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITION COMPRISING SAME AS EFFECTIVE INGREDIENT FOR PREVENTION OR TREATMENT OF CANCER OR INFLAMMATORY DISEASE<br/>[FR] DÉRIVÉ DE PYRIMIDINE SUBSTITUÉ EN POSITIONS 2, 4 ET 5, SON PROCÉDÉ DE PRÉPARATION, ET COMPOSITION PHARMACEUTIQUE LE COMPRENANT EN TANT QUE PRINCIPE ACTIF POUR LA PRÉVENTION OU LE TRAITEMENT DU CANCER OU D'UNE MALADIE INFLAMMATOIRE<br/>[KO] 2, 4, 5-치환된 피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 암 또는 염증질환의 예방 또는 치료용 약학적 조성물
  申请人：VORONOIBIO INC

  公开号：WO2019177374A1

  公开（公告）日：2019-09-19

  2, 4, 5-치환된 피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 암 또는 염증질환의 예방 또는 치료용 약학적 조성물에 관한 것이다. 상기 화합물은 EGFR(epidermal growth factor receptor) 야생형 또는 돌연변이에 대하여 높은 억제능을 나타내고, JAK3에 대한 억제효과가 우수하므로, EGFR 야생형 또는 EGFR 돌연변이가 발현된 암이나, JAK3의 활성과 관련된 암 또는 염증질환의 치료에 유용하게 사용될 수 있고, 폐암 세포주 증식 억제능이 우수한 바, 특히, 폐암의 치료에 유용하게 사용될 수 있다.