西维布林 | 849550-05-6

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 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: 西维布林
• 中文别名: 5-氯-6-[2,6-二氟-4-[3-(甲基氨基)丙氧基]苯基]-N-((1S)-2,2,2-三氟-1-甲基乙基)-[1,2,4]三唑并[1,5-a]嘧啶-7-胺；5-氯-6-[2,6-二氟-4-[3-(甲基氨基)丙氧基]苯基]-N-((1S)-2,2,2-三氟-1-甲基乙基)-[1,2,4]三唑并[1,5-A]嘧啶-7-胺
• 英文名称: cevipabulin
• 英文别名: (S)-5-chloro-6-(2,6-difluoro-4-(3-(methylamino)propoxy)phenyl)-N-(1,1,1-trifluoropropan-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine；5-chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
• CAS: 849550-05-6
• 化学式: C₁₈H₁₈ClF₅N₆O
• 分子量: 464.826
• InChiKey: ZUZPCOQWSYNWLU-VIFPVBQESA-N

物化性质

• 密度：
  1.52
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  76.4
• 氢给体数：
  2
• 氢受体数：
  11

安全信息

• 储存条件：
  2-8℃

制备方法与用途

Cevipabulin(TTI-237)是一种新型的微管抑制剂，其作用机制不同于其他的微管抑制剂。

反应信息

• 作为反应物：
  描述：

  西维布林 在 盐酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以provides 5-chloro-6-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine hydrogen chloride salt as a light yellow solid (2.92 g)的产率得到5-chloro-6-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine hydrogen chloride
  参考文献：
  名称：

  Crystalline forms of 5-Chloro-6-{2,6-difluoro-4-[3-(methylamino)propoxy]phenyl}-N-[(1S)-2,2,2-trifluoro-1-methylethyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine salts

  摘要：

  本发明涉及5-氯-6-{2,6-二氟-4-[3-(甲基氨基)丙氧基]苯基}-N-[(1S)-2,2,2-三氟甲基乙基][1,2,4]三唑[1,5-a]嘧啶-7-胺盐的晶体形态；其生产过程；药物组成物；以及用于抑制肿瘤生长的方法。

  公开号：

  US20070060597A1
• 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 hydride 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 9.0h， 生成 西维布林
  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

文献信息

• Design, synthesis and evaluation of photoactivatable derivatives of microtubule (MT)-active [1,2,4]triazolo[1,5-a]pyrimidines
  作者：Killian Oukoloff、Jane Kovalevich、Anne-Sophie Cornec、Yuemang Yao、Zachary A. Owyang、Michael James、John Q. Trojanowski、Virginia M.-Y. Lee、Amos B. Smith、Kurt R. Brunden、Carlo Ballatore

  DOI：10.1016/j.bmcl.2018.05.010

  日期：2018.7

  The [1,2,4]triazolo[1,5-a]pyrimidines comprise a promising class of non-naturally occurring microtubule (MT)-active compounds. Prior studies revealed that different triazolopyrimidine substitutions can yield molecules that either promote MT stabilization or disrupt MT integrity. These differences can have important ramifications in the therapeutic applications of triazolopyrimidines and suggest that

  [1,2,4]三唑并[1,5-a]嘧啶包括一类有前途的非天然存在的微管（MT）活性化合物。先前的研究表明，不同的三唑并嘧啶取代可产生促进MT稳定或破坏MT完整性的分子。这些差异在三唑并嘧啶的治疗应用中可能具有重要的意义，并表明不同的类似物可能在同一位点内表现出不同的结合模式，或者可能在其他结合位点与微管蛋白/ MT相互作用。为了帮助识别这些可能性，设计了一系列可光活化的三唑并嘧啶同源物，并在细胞测定中进行了评估，目的是鉴定用于光亲和标记实验的候选探针。这些研究导致鉴定出在三唑并嘧啶杂环的7位的胺取代基中掺入重氮基环的不同衍生物，从而导致促进MT稳定或破坏MT完整性的分子。这些可光活化的候选探针有望研究MT活性三唑并嘧啶的作用方式。
• [EN] 6-[(SUBSTITUTED)PHENYL]TRIAZOLOPYRIMIDINES AS ANTICANCER AGENTS<br/>[FR] 6-[(SUBSTITUTEES)PHENYL]TRIAZOLOPYRIMIDINES UTILISEES EN TANT QU'AGENT ANTICANCEREUX
  申请人：WYETH CORP

  公开号：WO2005030775A1

  公开（公告）日：2005-04-07

  This invention relates to certain 6-[(substituted)phenyl]triazolopyrimidine compounds or pharmaceutically acceptable salts thereof, and compositions containing said compounds or pharmaceutically acceptable salts 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 pharmaceutically acceptable salts thereof. 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.

  本发明涉及某些6-[(取代)苯基]三唑吡咯嗪化合物或其药用盐，以及含有所述化合物或其药用盐的组合物，其中所述化合物是对哺乳动物中的癌症具有治疗作用的抗癌剂。本发明还涉及一种治疗或抑制哺乳动物中癌症肿瘤细胞及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而具有耐药性的癌症肿瘤的方法，该方法包括向该哺乳动物施用所述化合物或其药用盐的有效量。本发明涉及一种通过促进微管聚合来治疗或抑制哺乳动物中癌症肿瘤细胞及相关疾病生长的方法，该方法包括向该哺乳动物施用所述化合物及其药用盐的有效量。
• Process for the preparation of tubulin inhibitors
  申请人：Wu Yanzhong

  公开号：US20050124635A1

  公开（公告）日：2005-06-09

  The present invention provides a process for the preparation of 6-[(substituted)phenyl]-triazolopyrimidine dicarboxylic acid salt and as a hydrated salt having the structural formula (I) wherein: R 1 is CF 3 or C 2 F 5 ; R 2 is H or C 1 -C 3 alkyl; n is an integer of 2, 3, or 4; X is Cl or Br; R 3 and R 4 are each independently H or C 1 -C 3 alkyl; or R 3 and R 4 when optionally taken together with the nitrogen atom to which each is attached form a 4 to 6 membered saturated heterocyclic ring having 1-2 nitrogen atoms and 0-1 oxygen atoms or 0-1 sulfur atoms, and optionally substituted with R 5 ; R 5 is C 1 -C 3 alkyl; wherein the dotted line is an optional bond.

  本发明提供了一种制备6-[(取代)苯基]-三唑吡咯嗪二羧酸盐和作为水合盐的过程，其具有结构式(I)，其中：R1为CF3或C2F5；R2为H或C1-C3烷基；n为2、3或4的整数；X为Cl或Br；R3和R4分别独立地为H或C1-C3烷基；或者当R3和R4与各自连接的氮原子一起形成1-2个氮原子和0-1个氧原子或0-1个硫原子的4至6个成员饱和杂环环，并可选地取代R5；R5为C1-C3烷基；其中虚线表示可选键。
• 6-[(Substituted)phenyl]triazolopyrimidines as anticancer agents
  申请人：Zhang Nan

  公开号：US20050090508A1

  公开（公告）日：2005-04-28

  This invention relates to certain 6-[(substituted)phenyl]triazolopyrimidine compounds or pharmaceutically acceptable salts thereof, and compositions containing said compounds or pharmaceutically acceptable salts 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 pharmaceutically acceptable salts thereof. 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.

  本发明涉及某些6-[(取代)苯基]三唑嘧啶化合物或其药学上可接受的盐，以及含有该化合物或其药学上可接受的盐的组合物，其中该化合物是对哺乳动物癌症治疗有用的抗癌剂。本发明还涉及一种用于治疗或抑制哺乳动物中癌细胞肿瘤的生长和相关疾病的方法，并进一步提供了一种用于治疗或预防因多药耐药（MDR）而表达多重药物抗性的癌性肿瘤的方法，该方法包括向所述哺乳动物中需要的部位注射所述化合物或其药学上可接受的盐的有效量。本发明还涉及一种通过促进微管聚合来治疗或抑制哺乳动物中癌细胞肿瘤的生长和相关疾病的方法，该方法包括向所述哺乳动物中注射所述化合物及其药学上可接受的盐的有效量。
• 6-[(substituted)phenyl]triazolopyrimidines as anticancer agents
  申请人：Wyeth

  公开号：US07507739B2

  公开（公告）日：2009-03-24

  This invention relates to certain 6-[(substituted)phenyl]triazolopyrimidine compounds or pharmaceutically acceptable salts thereof, and compositions containing said compounds or pharmaceutically acceptable salts 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 pharmaceutically acceptable salts thereof. 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.

  本发明涉及某些6-[(取代)苯基]三唑嘧啶化合物或其药学上可接受的盐，以及含有该化合物或其药学上可接受的盐的组合物，其中该化合物是用于治疗哺乳动物癌症的抗癌剂。本发明还涉及一种治疗或抑制哺乳动物癌性肿瘤细胞和相关疾病的方法，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而产生耐药性的癌性肿瘤的方法，其中该方法包括向该哺乳动物施用所述化合物或其药学上可接受的盐的有效量。本发明涉及一种通过促进微管聚合来治疗或抑制哺乳动物癌性肿瘤细胞和相关疾病的方法，该方法包括向该哺乳动物施用所述化合物及其药学上可接受的盐的有效量。