(4-氟-3-(三氟甲氧基)苯基)甲胺 | 886501-20-8

• 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: (4-氟-3-(三氟甲氧基)苯基)甲胺
• 英文名称: (4-fluoro-3-(trifluoromethoxy)phenyl)methanamine
• 英文别名: [4-fluoro-3-(trifluoromethoxy)phenyl]methanamine
• CAS: 886501-20-8
• 化学式: C₈H₇F₄NO
• mdl: MFCD06660254
• 分子量: 209.143
• InChiKey: LQEZTMITGPWONC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4-氟-3-(三氟甲氧基)苯基)甲胺 在 三乙胺 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 96.0h， 生成 N-(4-fluoro-3-(trifluoromethoxy)benzyl)-2-(2-(5-fluoropyrimidin-2-yl)ethyl)-3-oxoisoindoline-1-carboxamide
  参考文献：
  名称：

  3-Oxoisoindoline-1-carboxamides: Potent, State-Dependent Blockers of Voltage-Gated Sodium Channel Na_V1.7 with Efficacy in Rat Pain Models

  摘要：

  The voltage-gated sodium channel Na(V)1.7 is believed to be a critical mediator of pain sensation based on clinical genetic studies and pharmacological results. Clinical utility of nonselective sodium channel blockers is limited due to serious adverse drug effects. Here, we present the optimization, structure activity relationships, and in vitro and in vivo characterization of a novel series of Na(V)1.7 inhibitors based on the oxoisoindoline core. Extensive studies with focus on optimization of Na(V)1.7 potency, selectivity over Na(V)1.5, and metabolic stability properties produced several interesting oxoisoindoline carboxamides (16A, 26B, 28, 51, 60, and 62) that were further characterized. The oxoisoindoline carboxamides interacted with the local anesthetics binding site. In spite of this, several compounds showed functional selectivity versus Na(V)1.5 of more than 100-fold. This appeared to be a combination of subtype and state-dependent selectivity. Compound 28 showed concentration-dependent inhibition of nerve injury-induced ectopic in an ex vivo DRG preparation from SNL rats. Compounds 16A and 26B demonstrated concentration-dependent efficacy in preclinical behavioral pain models. The oxoisoindoline carboxamides series described here may be valuable for further investigations for pain therapeutics.

  DOI：

  10.1021/jm300623u

文献信息

• [EN] ARYLAMIDE DERIVATIVES AS TTX-S BLOCKERS<br/>[FR] DÉRIVÉS D'ARYLAMIDE EN TANT QU'AGENTS BLOQUANTS DE TTX-S
  申请人：RAQUALIA PHARMA INC

  公开号：WO2012053186A1

  公开（公告）日：2012-04-26

  The present invention relates to arylamide derivatives which have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved.

  本发明涉及具有对电压门控钠通道（如TTX-S通道）具有阻塞活性的芳基酰胺衍生物，用于治疗或预防涉及电压门控钠通道的疾病和疾病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗涉及电压门控钠通道的这类疾病中使用这些化合物和组合物。
• [EN] COMPOUNDS AS INHIBITORS OF DIACYLGLYCEROL O-ACYLTRANSFERASE TYPE 1 ENZYME<br/>[FR] COMPOSÉS COMME INHIBITEURS DE L'ENZYME DIACYLGLYCÉROL O-ACYLTRANSFÉRASE DE TYPE 1
  申请人：KAINOS MEDICINE INC

  公开号：WO2013119040A1

  公开（公告）日：2013-08-15

  The invention provides a novel compound having activity against diacylglycerol O-acyltransferase type 1 (DGAT1); a pharmaceutical composition for preventing or treating a disease, disorder or condition modulated by inhibition of DGAT1 comprising said compound; a method for preventing or treating a disease, disorder or condition modulated by inhibition of DGAT1 in an individual comprising administering said compound to the individual in need thereof; and a use of said compound for the manufacture of a medicament for preventing or treating a disease, disorder or condition modulated by DGAT1 inhibition.

  本发明提供了一种对二酰甘油O-酰基转移酶1（DGAT1）具有活性的新化合物；一种用于预防或治疗通过抑制DGAT1调节的疾病，障碍或病症的制剂，包括该化合物；一种预防或治疗个体中通过抑制DGAT1调节的疾病，障碍或病症的方法，包括向需要该化合物的个体施用该化合物；以及用于制造预防或治疗通过DGAT1抑制调节的疾病，障碍或病症的药物的该化合物的用途。
• Inhibitors of Ion Channels
  申请人：Marron Brian Edward

  公开号：US20130072471A1

  公开（公告）日：2013-03-21

  Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-gated sodium channels. More particularly, the invention provides substituted aryl sulfonamides, compositions comprising these compounds, as well as methods of using these compounds or compositions in the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrence of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a voltage-gated sodium channel.

  本发明提供了在通过抑制电压门控钠通道中的钠离子流来治疗疾病方面有用的化合物、组合物和方法。更具体地，本发明提供了取代芳基磺酰胺、包含这些化合物的组合物，以及使用这些化合物或组合物治疗中枢或外周神经系统疾病，特别是疼痛和慢性疼痛的方法，通过阻断与所示条件的发生或复发相关的钠通道来实现。本发明的化合物、组合物和方法特别适用于通过抑制电压门控钠通道中的离子流来治疗神经病性或炎症性疼痛。
• COMPOUNDS AS INHIBITORS OF DIACYLGLYCEROL O-ACYLTRANSFERASE TYPE I ENZYME
  申请人：KAINOS MEDICINE, INC.

  公开号：US20150157611A1

  公开（公告）日：2015-06-11

  The invention provides a novel compound having activity against diacylglycerol O-acyltransferase type 1 (DGAT1); a pharmaceutical composition for preventing or treating a disease, disorder or condition modulated by inhibition of DGAT1 comprising said compound; a method for preventing or treating a disease, disorder or condition modulated by inhibition of DGAT1 in an individual comprising administering said compound to the individual in need thereof; and a use of said compound for the manufacture of a medicament for preventing or treating a disease, disorder or condition modulated by DGAT1 inhibition.

  本发明提供了一种对二酰甘油O-酰基转移酶类型1（DGAT1）具有活性的新型化合物；一种用于预防或治疗受DGAT1抑制调节的疾病、紊乱或情况的药物组合物，包括该化合物；一种用于预防或治疗受DGAT1抑制调节的疾病、紊乱或情况的方法，包括向需要该化合物的个体施用该化合物；以及用于制造预防或治疗受DGAT1抑制调节的疾病、紊乱或情况的药物的该化合物的用途。
• ARYLAMIDE DERIVATIVES AS TTX-S BLOCKERS
  申请人：Yamagishi Tatsuya

  公开号：US20140336377A1

  公开（公告）日：2014-11-13

  The present invention relates to arylamide derivatives which have blocking activities of voltage gated sodium channels as the TTX-S channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved.

  本发明涉及一种芳基酰胺衍生物，其具有阻断电压门控钠通道（如TTX-S通道）的活性，并且在涉及电压门控钠通道的疾病和疾病的治疗或预防中有用。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在涉及电压门控钠通道的这种疾病的预防或治疗中的使用。