N-(3-(4-chloro-1,3,5-triazin-2-ylamino)-2-methylphenyl)acetamide | 1211876-60-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(3-(4-chloro-1,3,5-triazin-2-ylamino)-2-methylphenyl)acetamide
• 英文别名: N-[3-[(4-chloro-1,3,5-triazin-2-yl)amino]-2-methylphenyl]acetamide
• CAS: 1211876-60-6
• 化学式: C₁₂H₁₂ClN₅O
• 分子量: 277.713
• InChiKey: JYGZYCRHJIRLBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  79.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(3-(4-chloro-1,3,5-triazin-2-ylamino)-2-methylphenyl)acetamide 、 4-(4-(trifluoromethoxy)benzyloxy)piperidine trifluoroacetate salt 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以78%的产率得到N-[2-甲基-3-[[4-[4-[[4-(三氟甲氧基)苯基]甲氧基]-1-哌啶基]-1,3,5-三嗪-2-基]氨基]苯基]乙酰胺
  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：

  2,4-二氯-1,3,5-三嗪 、 N-(3-氨基-2-甲基苯基)乙酰胺 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以72%的产率得到N-(3-(4-chloro-1,3,5-triazin-2-ylamino)-2-methylphenyl)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

文献信息

• [EN] INHIBITORS OF VOLTAGE-GATED SODIUM CHANNELS<br/>[FR] INHIBITEURS DE CANAUX SODIQUES SENSIBLES AU POTENTIEL
  申请人：AMGEN INC

  公开号：WO2010022055A2

  公开（公告）日：2010-02-25

  The present invention provides compounds that are inhibitors of voltage-gated sodium channel (Nav), in particular Nav 1.7 and are therefore useful for the treatment of diseases 5 treatable by inhibition of these channels, in particular, chronic pain disorders. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
• 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.