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 | 1211866-85-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 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
• 英文名称: N-(2-methyl-3-(4-(4-(4-(trifluoromethoxy)benzyloxy)piperidin-1-yl)-1,3,5-triazin-2-ylamino)phenyl)acetamide
• 英文别名: N-[2-methyl-3-[[4-[4-[[4-(trifluoromethoxy)phenyl]methoxy]piperidin-1-yl]-1,3,5-triazin-2-yl]amino]phenyl]acetamide
• CAS: 1211866-85-1
• 化学式: C₂₅H₂₇F₃N₆O₃
• 分子量: 516.523
• InChiKey: QLKAFHZJICDACE-UHFFFAOYSA-N

物化性质

• 密度：
  1.37±0.1 g/cm3(Predicted)
• 溶解度：
  在 DMSO 中溶解至 100 mM，在 1eq 中溶解至 10 mM。盐酸

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  4-三氟甲氧基溴苄 在 sodium hydride 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 40.0h， 生成 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

文献信息

• TOPICAL OCULAR ANALGESIC AGENTS
  申请人：Novartis AG

  公开号：US20140228338A1

  公开（公告）日：2014-08-14

  The topical ophthalmic use of certain 2,4-diamino-substituted 1,3-triazines for preventing or alleviating ocular pain in patients is disclosed. Topcial ocular pharmaceutical composition are also disclosed.
• US9187468B2
  申请人：——

  公开号：US9187468B2

  公开（公告）日：2015-11-17
• [EN] TOPICAL OCULAR ANALGESIC AGENTS<br/>[FR] AGENTS ANALGÉSIQUES OCULAIRES TOPIQUES
  申请人：NOVARTIS AG

  公开号：WO2014127116A1

  公开（公告）日：2014-08-21

  The topical ophthalmic use of certain 2,4-diamino-substituted 1,3-triazines for preventing or alleviating ocular pain in patients is disclosed. Topcial ocular pharmaceutical composition are also disclosed.
• 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.