2-(6-chloropyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline | 1121625-27-1

• 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-(6-chloropyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 2-(6-Chloro-4-pyrimidinyl)-1,2,3,4-tetrahydroisoquinoline；2-(6-chloropyrimidin-4-yl)-3,4-dihydro-1H-isoquinoline
• CAS: 1121625-27-1
• 化学式: C₁₃H₁₂ClN₃
• mdl: MFCD10000665
• 分子量: 245.711
• InChiKey: VFUDDEGKULGUMP-UHFFFAOYSA-N

物化性质

• 沸点：
  432.1±45.0 °C(Predicted)
• 密度：
  1.293±0.06 g/cm3(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

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-(6-chloropyrimidin-4-yl)-1,2,3,4-tetrahydroisoquinoline 、 间氨基乙酰苯胺 在 三氟乙酸 作用下， 以 异丙醇 为溶剂， 以34.2%的产率得到N-(3-(6-(3,4-dihydroisoquinolin-2(1H)-yl)pyrimidin-4-ylamino)phenyl)acetamide
  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
• 作为产物：
  描述：

  4,6-二氯嘧啶 、 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 1.0h， 以82%的产率得到2-(6-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

• SUBSTITUTED (PIPERIDIN-1-YL)ARYL ANALOGUES FOR MODULATING AVIL ACTIVITY
  申请人：University of Virginia Patent Foundation

  公开号：US20220213055A1

  公开（公告）日：2022-07-07

  In one aspect, the disclosure relates to compounds useful to regulate, limit, or inhibit the expression of AVIL (advillin), methods of making same, pharmaceutical compositions comprising same, and methods of treating disorders associated with AVIL dysregulation using same. In aspects, the disclosed compounds, compositions and methods are useful for treating disorders or diseases in which the regulation, limitation, or inhibition of the expression of AVIL can be clinically useful, such as, for example, the treatment of cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
• 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.