4,6-二氯-2-吡嗪-2-基-5-(2,4,6-三氟苯基)嘧啶 | 849600-51-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4,6-二氯-2-吡嗪-2-基-5-(2,4,6-三氟苯基)嘧啶
• 英文名称: 4,6-dichloro-2-(pyrazin-2-yl)-5-(2,4,6-trifluorophenyl)pyrimidine
• 英文别名: 4,6-dichloro-2-pyrazin-2-yl-5-(2,4,6-trifluorophenyl)pyrimidine；4,6-dichloro-2-pyrazin-2-yl-5-(2,4,6-trifluoro-phenyl)-pyrimidine
• CAS: 849600-51-7
• 化学式: C₁₄H₅Cl₂F₃N₄
• 分子量: 357.122
• InChiKey: SAWHIQMQGZZGTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 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：
  51.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4,6-二氯-2-吡嗪-2-基-5-(2,4,6-三氟苯基)嘧啶 在 sodium hydride 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 20.0h， 生成 (S)-6-chloro-5-(4-(3-(dimethylamino)propoxy)-2,6-difluorophenyl)-2-(pyrazin-2-yl)-N-(1,1,1-trifluoropropan-2-yl)pyrimidin-4-amine
  参考文献：
  名称：

  [EN] HETEROCYCLIC COMPOUNDS AND THEIR USE FOR THE TREATMENT OF NEURODEGENERATIVE TAUOPATHIES
  [FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION POUR LE TRAITEMENT DE TAUOPATHIES NEURODÉGÉNÉRATIVES

  摘要：

  公开号：

  WO2014047257A3
• 作为产物：
  描述：

  2,4,6-三氟苯基丙二酸二乙酯 在 三正丁胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 反应 8.0h， 生成 4,6-二氯-2-吡嗪-2-基-5-(2,4,6-三氟苯基)嘧啶
  参考文献：
  名称：

  Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

  摘要：

  Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer's disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD patients. Furthermore, this natural product exhibits potential deficiencies as a drug candidate, including an intravenous route of administration and the inhibition of the P-glycoprotein (Pgp) transporter. Thus, the identification of alternative CNS-active MT-stabilizing agents that lack these potential limitations is of interest. Toward this objective, we have evaluated representative compounds from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function. Pharmacodynamic studies confirmed that representative compounds from these series enhance MT-stabilization in the brains of wild-type mice. Thus, these classes of MT-stabilizers hold promise for the development of orally active, CNS-directed MT-stabilizing therapies.

  DOI：

  10.1021/jm5005623
• 作为试剂：
  描述：

  2-pyrazin-2-yl-5-(2,4,6-trifluorophenyl)pyrimidine-4,6-diol 、 三氯氧磷 、 N,N-二异丙基乙胺 、 二氯甲烷 在 甲苯 、 水 、 Sodium sulfate-III 、 Forsterite 、 正庚烷 、 4,6-二氯-2-吡嗪-2-基-5-(2,4,6-三氟苯基)嘧啶 作用下， 以 乙酸乙酯 、 甲苯 为溶剂， 反应 30.0h， 以Further, the 4,6-dichloro-2-pyrazin-2-yl-5-(2,4,6-trifluoro-phenyl)-pyrimidine 5 is formed的产率得到4,6-二氯-2-吡嗪-2-基-5-(2,4,6-三氟苯基)嘧啶
  参考文献：
  名称：

  Tubulin inhibitor and process for its preparation

  摘要：

  该发明提供了6-氯-5-{2,6-二氟-4-[3-(甲基氨基)丙氧基]苯基}-2-吡嗪-2-基-N-[(1S)-2,2,2-三氟-1-甲基乙基]嘧啶-4-胺富馬酸半盐，该化合物是一种微管蛋白抑制剂，可用于治疗癌症，同时还提供了制备该半盐的方法。

  公开号：

  US07501423B2

文献信息

• 5-arylpyrimidines as anticancer agents
  申请人：Zhang Nan

  公开号：US20050075357A1

  公开（公告）日：2005-04-07

  This invention relates to certain 5-arylpyrimidine compounds or a pharmaceutically acceptable salt thereof, and compositions containing said compounds or a pharmaceutically acceptable salt thereof, wherein said compounds are anti-cancer agents useful for the treatment of cancer in mammals. This invention further relates to a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal and further provides a method for the treatment or prevention of cancerous tumors that express multiple drug resistance (MDR) or are resistant because of MDR, in a mammal in need thereof which method comprises administering to said mammal an effective amount of said compounds or a pharmaceutically acceptable salt thereof. More specifically, the present invention relates to a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal in need thereof by promotion of microtubule polymerization which comprises administering to said mammal an effective amount of said compounds and pharmaceutically acceptable salts thereof.

  这项发明涉及某些5-芳基嘧啶化合物或其药用盐，以及含有所述化合物或其药用盐的组合物，其中所述化合物是抗癌剂，可用于治疗哺乳动物的癌症。该发明还涉及一种治疗或抑制哺乳动物体内癌细胞和相关疾病生长的方法，并进一步提供了一种治疗或预防表达多药耐药性（MDR）或因MDR耐药的癌症肿瘤的方法，该方法包括向所述哺乳动物体内施用所述化合物或其药用盐的有效量。更具体地，本发明涉及通过促进微管聚合来治疗或抑制哺乳动物体内癌细胞和相关疾病的方法，该方法包括向所述哺乳动物体内施用所述化合物及其药用盐的有效量。
• Synthesis and SAR of 6-chloro-4-fluoroalkylamino-2-heteroaryl-5-(substituted)phenylpyrimidines as anti-cancer agents
  作者：Nan Zhang、Semiramis Ayral-Kaloustian、Thai Nguyen、Richard Hernandez、Judy Lucas、Carolyn Discafani、Carl Beyer

  DOI：10.1016/j.bmc.2008.11.016

  日期：2009.1

  ortho-position to the pyrimidyl core. The structure–activity relationship for the rest of the molecule in this 2-heteroarylpyrimidine series mimics that of the [1,2,4]triazolo[1,5-a]pyrimidine series. Like triazolopyrimidines and 2-cyanoaminopyrimidines, the 2-heteroarylpyrimidines retain the capability to overcome multidrug resistance due to Pgp. Mechanism of action studies showed that the lead compounds behaved

  描述了一系列的6-氯-4-氟烷基氨基-2-杂芳基-5-（取代）苯基嘧啶作为抗癌剂的合成和SAR。这一系列的2-杂芳基嘧啶是通过修饰我们先前报道的一系列抗肿瘤[1,2,4]三唑并[1,5- a ]嘧啶和2-氰基氨基嘧啶而开发的。对于2-杂芳基，当杂芳基在嘧啶基核的邻位具有氮原子时，可获得最佳活性。该2-杂芳基嘧啶系列中其余分子的结构-活性关系类似于[1,2,4]三唑[1,5- a ]的结构-活性关系]嘧啶系列。像三唑并嘧啶和2-氰基氨基嘧啶一样，2-杂芳基嘧啶保留克服由于Pgp引起的多药耐药性的能力。作用机理研究表明，先导化合物的行为与三唑并嘧啶和2-氰基氨基嘧啶相同。在体外和体内，该系列中的先导化合物比相应的三唑并嘧啶更有效。化合物21（PTI-868）在几种裸鼠异种移植模型中均显示出抑制肿瘤生长的作用，因此被选择进行临床前开发。
• HETEROCYCLIC COMPOUNDS AND THEIR USE FOR THE TREATMENT OF NEURODEGENERATIVE TAUOPATHIES
  申请人：THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

  公开号：US20150224105A1

  公开（公告）日：2015-08-13

  The present invention is directed to triazolopyrimidine, phenylpyrimidine, pyridopyridazine, and pyridotriazine compounds which are microtubule-stabilizing compounds and their use in the treatment of neurodegenerative disorders, in particular, tauopathies, such as for example, Alzheimer's disease, frontotemporal lobar degeneration, Pick's disease, progressive supranuclear palsy (PSP), and corticobasal degeneration. In addition, the compounds of the invention may be useful for other diseases where tau pathology is a comorbidity or where microtubule function is compromised, for example, schizophrenia, Parkinson's disease (PD), PD with dementia, Lewy body disease with dementia, and amyotrophic lateral sclerosis.

  本发明涉及三唑并嘧啶、苯基嘧啶、吡啶并吡嗪和吡啶并三嗪类化合物，它们是微管稳定剂化合物，以及它们在治疗神经退行性疾病中的应用，特别是tau病理学，例如阿尔茨海默病、额颞叶变性、皮克氏病、进展性上皮核瘤和皮质基底节变性。此外，本发明中的化合物也可能对其他tau病理学是共病或微管功能受损的疾病有用，例如精神分裂症、帕金森病（PD）、带有痴呆的PD、带有痴呆的Lewy体病和肌萎缩侧索硬化症。
• 5-ARYLPYRIMIDINES AS ANTICANCER AGENTS
  申请人：Wyeth Holdings Corporation

  公开号：EP1663241A1

  公开（公告）日：2006-06-07
• TUBULIN INHIBITOR AND PROCESS FOR ITS PREPARATION
  申请人：Wyeth

  公开号：EP1891052A1

  公开（公告）日：2008-02-27