2-(2-chloropyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline | 954226-81-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 2-(2-chloropyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 2-(2-chloropyrimidin-4-yl)-3,4-dihydro-1H-isoquinoline
• CAS: 954226-81-4
• 化学式: C₁₃H₁₂ClN₃
• mdl: MFCD09750057
• 分子量: 245.711
• InChiKey: HPNPORHBFJRDDL-UHFFFAOYSA-N

物化性质

• 沸点：
  450.240±40.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.294±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  29
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2-chloropyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline 在 三乙烯二胺 、 palladium diacetate 、 乙酰氯 、 三苯基膦 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 27.0h， 生成 methyl 4-(3,4-dihydroisoquinolin-2(1H)-yl)pyrimidine-2-carboxylate
  参考文献：
  名称：

  Structure-activity relationships of 2-pyrimidinecarbohydrazides as utrophin modulators for the potential treatment of Duchenne muscular dystrophy

  摘要：

  DOI：

  10.1016/j.bmc.2022.116812
• 作为产物：
  描述：

  2,4-二氯嘧啶 、 四氢异喹啉 在 N,N-二异丙基乙胺 作用下， 以 异丙醇 为溶剂， 反应 24.25h， 以88%的产率得到2-(2-chloropyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Identification of a Potent, State-Dependent Inhibitor of Nav1.7 with Oral Efficacy in the Formalin Model of Persistent Pain

  摘要：

  Clinical human genetic studies have recently identified the tetrodotoxin (TTX) sensitive neuronal voltage gated sodium channel Nav1.7 (SCN9A) as a critical mediator of pain sensitization. Herein, we report structure-activity relationships for a novel series of 2,4-diaminotriazines that inhibit hNav1.7. Optimization efforts culminated in compound 52, which demonstrated pharmacokinetic properties appropriate for in vivo testing in rats. The binding site, of compound 52 on Nav1.7 was determined to be distinct from that of local anesthetics. Compound 52 inhibited tetrodotoxin-sensitive sodium channels recorded from rat sensory neurons and exhibited modest selectivity against the hERG potassium channel and against cloned and native tetrodotoxin-resistant sodium channels. Upon oral administration to rats, compound 52 produced dose- and exposure-dependent efficacy in the formalin model of pain.

  DOI：

  10.1021/jm200018k

文献信息

• Identification of a Potent, State-Dependent Inhibitor of Nav1.7 with Oral Efficacy in the Formalin Model of Persistent Pain
  作者：Howard Bregman、Loren Berry、John L. Buchanan、April Chen、Bingfan Du、Elma Feric、Markus Hierl、Liyue Huang、David Immke、Brett Janosky、Danielle Johnson、Xingwen Li、Joseph Ligutti、Dong Liu、Annika Malmberg、David Matson、Jeff McDermott、Peter Miu、Hanh Nho Nguyen、Vinod F. Patel、Daniel Waldon、Ben Wilenkin、Xiao Mei Zheng、Anruo Zou、Stefan I. McDonough、Erin F. DiMauro

  DOI：10.1021/jm200018k

  日期：2011.7.14

  Clinical human genetic studies have recently identified the tetrodotoxin (TTX) sensitive neuronal voltage gated sodium channel Nav1.7 (SCN9A) as a critical mediator of pain sensitization. Herein, we report structure-activity relationships for a novel series of 2,4-diaminotriazines that inhibit hNav1.7. Optimization efforts culminated in compound 52, which demonstrated pharmacokinetic properties appropriate for in vivo testing in rats. The binding site, of compound 52 on Nav1.7 was determined to be distinct from that of local anesthetics. Compound 52 inhibited tetrodotoxin-sensitive sodium channels recorded from rat sensory neurons and exhibited modest selectivity against the hERG potassium channel and against cloned and native tetrodotoxin-resistant sodium channels. Upon oral administration to rats, compound 52 produced dose- and exposure-dependent efficacy in the formalin model of pain.
• Design, synthesis, docking, molecular dynamics and bioevaluation studies on novel N-methylpicolinamide and thienopyrimidine derivatives with inhibiting NF-κB and TAK1 activities: Cheminformatics tools RDKit applied in drug design
  作者：Linxiao Wang、Qian Zhang、Zhe Wang、Wufu Zhu、Ninghua Tan

  DOI：10.1016/j.ejmech.2021.113576

  日期：2021.11
• Design, Synthesis, and Preliminary Activity Evaluation of Novel Pyrimidine Derivatives as Acid Pump Antagonists
  作者：Weiguo Song、Xiaopan Zhang、Shutao Li、Wenfang Xu

  DOI：10.1111/cbdd.12390

  日期：2015.3

  Acid‐related diseases of the upper gastrointestinal tract, especially gastroesophageal reflux disease (GERD), remain a widespread problem worldwide. In this paper, we reported the design, synthesis, and preliminary gastric antisecretory activity evaluation of novel pyrimidine derivatives as acid pump antagonists. The gastric antisecretory activity assay results showed that all compounds displayed potent gastric antisecretory activity when gastric secretion was stimulated by histamine. The most potent compound 5g exhibited even similar gastric antisecretory activity compared with the control revaprazan, and the relative inhibition rate was 93.0%, which was worthy of further investigation.
• Structure-activity relationships of 2-pyrimidinecarbohydrazides as utrophin modulators for the potential treatment of Duchenne muscular dystrophy
  作者：Maria Chatzopoulou、Daniel Conole、Enrico Emer、Jessica A. Rowley、Nicky J. Willis、Sarah E. Squire、Becky Gill、Steve Brough、Francis X. Wilson、Graham M. Wynne、Stephen G. Davies、Kay E. Davies、Angela J. Russell

  DOI：10.1016/j.bmc.2022.116812

  日期：2022.9