7-chloro-2-(chloromethyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidine | 75125-83-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 7-chloro-2-(chloromethyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidine
• 英文别名: 7-Chloro-2-(chloromethyl)-5-methyl-[1,2,4]triazolo[1,5-A]pyrimidine
• CAS: 75125-83-6
• 化学式: C₇H₆Cl₂N₄
• 分子量: 217.057
• InChiKey: ZVOYKKFXDAPPRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-chloro-2-(chloromethyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidine 以 四氢呋喃 、 乙醇 为溶剂， 生成 N-(4-chlorophenyl)-5-methyl-2-((methylamino)methyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
  参考文献：
  名称：

  Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

  摘要：

  Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model, can be synthesized by a simple route, and rodent pharmaco-kinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.

  DOI：

  10.1021/jm200592f
• 作为产物：
  描述：

  2,3-Diamino-6-methyl-4(3H)-pyrimidinone 在 三氯氧磷 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 7-chloro-2-(chloromethyl)-5-methyl[1,2,4]triazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

  摘要：

  Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model, can be synthesized by a simple route, and rodent pharmaco-kinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.

  DOI：

  10.1021/jm200592f

文献信息

• NOVEL s-TRIAZOLE(1,5-a)PYRIMIDINE DERIVATIVES
  申请人：MOCHIDA PHARMACEUTICAL CO., LTD.

  公开号：EP0101517A1

  公开（公告）日：1984-02-29

  Novel s-triazole[1,5-a]pyrimidine derivatives represented by the general formula (I): wherein R, and R2 may be the same or different and each represents a straight or branched alkyl group containing 1 to 6 carbon atoms, a phenyl group or a hydrogen atom, R3 represents a straight or branched alkyl group containing 1 to 6 carbon atoms or a hydrogen atom, R4 represents a straight or branched alkyl group containing 1 to 6 carbon atoms, a phenyl group or a substituted phenyl group, and R5 represents a hydrogen atom or R5 and R, together form a -(CH2)- group. The compounds have vasodilating, hypotensive and blood platelet agglutination-preventing effects, and are useful for treating diseases of circulatory organs.

  通式(I)代表的新型 s-三唑[1,5-a]嘧啶衍生物： 其中 R 和 R2 可以相同或不同，各自代表含有 1 至 6 个碳原子的直链或支链烷基、苯基或氢原子；R3 代表含有 1 至 6 个碳原子的直链或支链烷基或氢原子；R4 代表含有 1 至 6 个碳原子的直链或支链烷基、苯基或取代苯基；R5 代表氢原子或 R5 和 R 共同形成-(CH2)-基团。这些化合物具有扩张血管、降血压和防止血小板凝集的作用，可用于治疗循环器官疾病。
• ONISI, XARUO;KOSE, XIROSI
  作者：ONISI, XARUO、KOSE, XIROSI

  DOI：——

  日期：——
• ONISI, XARUO;KOSASAKI, KODZI;SUDZUKI, YASUO;MOTIDA, XIDEH
  作者：ONISI, XARUO、KOSASAKI, KODZI、SUDZUKI, YASUO、MOTIDA, XIDEH

  DOI：——

  日期：——
• ONISI, XARUO;SUDZUKI, YASUO;MOTIDA, EHJ
  作者：ONISI, XARUO、SUDZUKI, YASUO、MOTIDA, EHJ

  DOI：——

  日期：——
• OHNISHI, HARUO;KOSUZUME, HIROSHI;SUZUKI, YASUO;MOCHIDA, EI
  作者：OHNISHI, HARUO、KOSUZUME, HIROSHI、SUZUKI, YASUO、MOCHIDA, EI

  DOI：——

  日期：——