N-(3,5-bis-trifluoromethyl-benzyl)-6-(4-hydroxyacetyl-piperazin-1-yl)-N-methyl-4-o-tolyl-nicotinamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(3,5-bis-trifluoromethyl-benzyl)-6-(4-hydroxyacetyl-piperazin-1-yl)-N-methyl-4-o-tolyl-nicotinamide
• 英文别名: N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-6-[4-(2-hydroxyacetyl)piperazin-1-yl]-N-methyl-4-(2-methylphenyl)pyridine-3-carboxamide
• 化学式: C₂₉H₂₈F₆N₄O₃
• 分子量: 594.557
• InChiKey: BOMJIRPTWVYTER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  42
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  77
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  N-(3,5-bis-trifluoromethyl-benzyl)-6-(4-bromoacetyl-piperazin-1-yl)-N-methyl-4-o-tolyl-nicotinamide 、 碳酸氢钠 在 水 、 甲基叔丁基醚 、 Sodium sulfate-III 作用下， 以 N-甲基吡咯烷酮 为溶剂， 25.0~100.0 ℃ 、6.67 kPa 条件下， 以Flash column chromatography afforded 71 mg (64%) of the title compound as a white solid的产率得到N-(3,5-bis-trifluoromethyl-benzyl)-6-(4-hydroxyacetyl-piperazin-1-yl)-N-methyl-4-o-tolyl-nicotinamide
  参考文献：
  名称：

  Substituted 4-phenyl-pyridine compounds with activity as antagonists of neurokinin 1 receptors

  摘要：

  具有神经激肽1受体拮抗剂活性的4-苯基吡啶化合物的替代物，制备这些化合物的方法和制备方法。

  公开号：

  US06770637B2

文献信息

• Use of NK-1 receptor antagonists against benign prostatic hyperplasia
  申请人：——

  公开号：US20030004157A1

  公开（公告）日：2003-01-02

  The invention relates to the use of an NK-1 receptor antagonist for the treatment or prevention of benign prostatic hyperplasia (BPH). The preferred NK-1 receptor antagonists are compounds of the general formula 1 wherein the meanings of R, R 1 , R 2 , R 2′ , R 3 , R 4 are explained in the specification and the pharmaceutically acceptable acid addition salts and the prodrugs thereof Preferred compounds are 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide, 2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-N-[6-(4-methyl-piperazin-1-yl)-4-o-tolyl-pyridin-3-yl]-isobutyramide, 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxo-1&lgr; 6 -thiomorpholin-4-yl)-4-o-tolyl-pyridin-3-yl]-N-methyl-isobutyramide and 2-(3,5-bis-trifluoromethyl-phenyl)-N-[6-(1,1-dioxo-1&lgr; 6 -thiomorpholin-4-yl)-4-(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-N-methyl-isobutyramide. The invention also relates to pharmaceutical composition comprising one or more such NK-1 receptor antagonists and a pharmaceutically acceptable excipient for the treatment and/or prevention of benign prostatic hyperplasia.

  本发明涉及使用NK-1受体拮抗剂治疗或预防良性前列腺增生（BPH）。首选的NK-1受体拮抗剂是一般式1中R，R1，R2，R2'，R3，R4的含义在规范中解释的化合物，以及其药学上可接受的酸盐和前药。首选化合物是2-(3,5-双三氟甲基苯基)-N-甲基-N-(6-吗啉-4-基-4-o-甲苯基-吡啶-3-基)-异丁酰胺，2-(3,5-双三氟甲基苯基)-N-甲基-N-[6-(4-甲基哌嗪-1-基)-4-o-甲苯基-吡啶-3-基]-异丁酰胺，2-(3,5-双三氟甲基苯基)-N-[6-(1,1-二氧-1&lgr;6-硫代吗啉-4-基)-4-o-甲苯基-吡啶-3-基]-N-甲基异丁酰胺和2-(3,5-双三氟甲基苯基)-N-[6-(1,1-二氧-1&lgr;6-硫代吗啉-4-基)-4-(4-氟-2-甲基苯基)-吡啶-3-基]-N-甲基异丁酰胺。本发明还涉及包含一种或多种此类NK-1受体拮抗剂和药学上可接受的载体的制药组合物，用于治疗和/或预防良性前列腺增生。
• Method of treatment and/or prevention of brain, spinal or nerve injury
  申请人：——

  公开号：US20030083345A1

  公开（公告）日：2003-05-01

  The invention relates to a method of treatment and/or prevention of brain, spinal or nerve injury comprising administration to a person in need of such treatment, of a therapeutically effective amount of an NK-1 receptor antagonist compound of the formula 1 wherein the meanings of R, R 1 , R 2 , R 2′ , R 3 , R 4 are explained in the specification and the pharmaceutically acceptable acid addition salts and the prodrugs thereof either alone or in combination with a magnesium salt. Exemplified is the use of N-(3,5-bis-trifluoromethyl-benzyl)-N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide. The invention also relates to pharmaceutical composition comprising one or more such NK-1 receptor antagonists, optionally in combination with a magnesium salt, and a pharmaceutically acceptable excipient for the treatment and/or prevention of brain, spinal or nerve injury.

  本发明涉及一种治疗和/或预防脑、脊髓或神经损伤的方法，包括向需要此类治疗的人口中给予公式1的NK-1受体拮抗剂化合物的治疗有效量，其中R、R1、R2、R2′、R3、R4的含义在说明书中解释，其药学可接受的酸盐和其前药，可以单独使用或与镁盐组合使用。例如使用N-(3,5-双三氟甲基苯基)-N-甲基-6-(4-甲基哌嗪-1-基)-4-邻甲苯基烟酰胺。本发明还涉及一种制药组合物，包括一种或多种这样的NK-1受体拮抗剂，可选地与镁盐组合使用，以及药学可接受的载体，用于治疗和/或预防脑、脊髓或神经损伤。
• The use of pyridinic NK-1 receptor antagonists for the treatment of brain, spinal or nerve injury
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1621195A2

  公开（公告）日：2006-02-01

  The invention relates to the use of an NK-1 receptor antagonist, optionally in combination with a magnesium salt, for the treatment and/or prevention of brain, spinal or nerve injury, wherein said NK-1 receptor antagonist is a compound of the general formula wherein the meanings of R, R1, R2, R2', R3, R4 are explained in the specification and the pharmaceutically acceptable acid addition salts and the prodrugs thereof either alone or in combination with a magnesium salt. Exemplified is the use of N-(3,5-bis-trifluoromethylbenzyl)-N-methyl-6-(4-methyl-piperazin-1-yl)-4-o-tolyl-nicotinamide. The invention also relates to pharmaceutical composition comprising one or more such NK-1 receptor antagonists, optionally in combination with a magnesium salt, and a pharmaceutically acceptable excipient for the treatment and/or prevention of brain, spinal or nerve injury.

  本发明涉及一种 NK-1 受体拮抗剂（可选择与镁盐结合使用）用于治疗和/或预防脑、脊柱或神经损伤，其中所述 NK-1 受体拮抗剂为通式化合物 其中 R、R1、R2、R2'、R3、R4 的含义在说明书中解释，其药学上可接受的酸加成盐和原药可单独使用或与镁盐结合使用。例如，N-(3,5-双三氟甲基苄基)-N-甲基-6-(4-甲基-哌嗪-1-基)-4-邻甲苯基烟酰胺的用途。本发明还涉及药物组合物，该组合物包含一种或多种此类 NK-1 受体拮抗剂（可选择与镁盐结合使用）和药学上可接受的赋形剂，用于治疗和/或预防脑、脊柱或神经损伤。
• Compositions and therapeutic methods utilizing a combination of a protein extravasation inhibitor and an NSAID
  申请人：Plachetka R. John

  公开号：US20060178348A1

  公开（公告）日：2006-08-10

  The present invention is directed to compositions containing an anti-inflammatory compound that acts by blocking protein extravasation together with an NSAID. These compositions may be used to treat inflammation and pain, especially headache pain. The invention also includes methods in which these drugs are separately administered to a patient.

  本发明涉及含有一种通过阻断蛋白质外渗发挥作用的抗炎化合物和一种非甾体抗炎药的组合物。这些组合物可用于治疗炎症和疼痛，尤其是头痛。本发明还包括向患者分别施用这些药物的方法。
• 4-PHENYL-PYRIDINE DERIVATIVES AS NEUROKININ-1 RECEPTOR ANTAGONISTS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1309559B1

  公开（公告）日：2006-06-07