1-methyl-N-(oxan-4-yl)-N-{[3-(trifluoromethoxy)phenyl]methyl}-1H-imidazole-4-carboxamide | 1245711-60-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-methyl-N-(oxan-4-yl)-N-{[3-(trifluoromethoxy)phenyl]methyl}-1H-imidazole-4-carboxamide
• 英文别名: 1-Methyl-N-(tetrahydro-2H-pyran-4-yl)-N-[3-(trifluoromethoxy)benzyl]-1H-imidazole-4-carboxamide；1-methyl-N-(oxan-4-yl)-N-[[3-(trifluoromethoxy)phenyl]methyl]imidazole-4-carboxamide
• CAS: 1245711-60-7
• 化学式: C₁₈H₂₀F₃N₃O₃
• 分子量: 383.37
• InChiKey: DHGSGWYSTPVWMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  56.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-三氟甲氧基苄胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 2.5h， 生成 1-methyl-N-(oxan-4-yl)-N-{[3-(trifluoromethoxy)phenyl]methyl}-1H-imidazole-4-carboxamide
  参考文献：
  名称：

  GLYCINE TRANSPORTER INHIBITING SUBSTANCES

  摘要：

  本发明旨在提供基于甘氨酸摄取抑制作用的新型化合物，其化学式为[I]或其药学上可接受的盐，可用于预防或治疗精神分裂症、阿尔茨海默病、认知功能障碍、痴呆、焦虑障碍（广泛性焦虑障碍、恐慌障碍、强迫性障碍、社交焦虑障碍、创伤后应激障碍、特定恐惧症、急性应激障碍等）、抑郁症、药物成瘾、痉挛、震颤和睡眠障碍等疾病的治疗。

  公开号：

  US20120010414A1

文献信息

• Identification of 1-Methyl-<i>N</i>-(propan-2-yl)-<i>N</i>-({2-[4-(trifluoromethoxy)phenyl]pyridin-4-yl}methyl)-1<i>H</i>-imidazole-4-carboxamide as a Potent and Orally Available Glycine Transporter 1 Inhibitor
  作者：Shuji Yamamoto、Hiroshi Ohta、Kumi Abe、Daiji Kambe、Naohiro Tsukiyama、Yasunori Kawakita、Minoru Moriya、Akito Yasuhara

  DOI：10.1248/cpb.c16-00610

  日期：——

  We previously identified 3-chloro-N-(S)-[3-(1-ethyl-1H-pyrazol-4-yl)phenyl][(2S)-piperidine-2-yl]methyl}-4-(trifluoromethyl)pyridine-2-carboxamide (5, TP0439150) as a potent and orally available glycine transporter 1 (GlyT1) inhibitor. In this article, we describe our identification of 1-methyl-N-(propan-2-yl)-N-(2-[4-(trifluoromethoxy)phenyl]pyridin-4-yl}methyl)-1H-imidazole-4-carboxamide (7n) as a structurally diverse back-up compound of 5, using central nervous system multiparameter optimization (CNS MPO) as a drug-likeness guideline. Compound 7n showed a higher CNS MPO score and different physicochemical properties as compared to 5. Compound 7n exhibited potent GlyT1 inhibitory activity, a favorable pharmacokinetics profile, and elicited an increase in the cerebrospinal fluid (CSF) concentration of glycine in rats.

  我们之前确定了一种强大的且可通过口服的甘氨酸转运蛋白1（GlyT1）抑制剂，即3-氯-N-(S)-[3-(1-乙基-1H-吡唑-4-基)苯基][(2S)-哌啶-2-基]甲基}-4-(三氟甲基)吡啶-2-羧酰胺（5，TP0439150）。在本文中，我们描述了我们通过中枢神经系统多参数优化（CNS MPO）作为类药性指导原则，识别出结构多样性的备选化合物1-甲基-N-(丙-2-基)-N-(2-[4-(三氟甲氧基)苯基]吡啶-4-基}甲基)-1H-咪唑-4-羧酰胺（7n）作为5的备份化合物。与5相比，化合物7n显示出更高的CNS MPO得分和不同的物理化学性质。化合物7n表现出强大的GlyT1抑制活性，良好的药代动力学特性，并能增加大鼠脑脊液（CSF）中甘氨酸的浓度。
• Glycine transporter inhibiting substances
  申请人：Yasuhara Akito

  公开号：US08623898B2

  公开（公告）日：2014-01-07

  The present invention aims to provide novel compounds of formula [I] or pharmaceutically acceptable salts thereof that are based on a glycine uptake inhibiting action and which are useful in the prevention or treatment of such diseases as schizophrenia, Alzheimer's disease, cognitive dysfunction, dementia, anxiety disorders (generalized anxiety disorder, panic disorder, obsessive-compulsory disorder, social anxiety disorder, posttraumatic stress disorder, specific phobia, acute stress disorder, etc.), depression, drug addiction, spasm, tremor, and sleep disorder:

  本发明旨在提供公式[I]的新化合物或其药学上可接受的盐，其基于甘氨酸摄取抑制作用，并且在预防或治疗精神分裂症、阿尔茨海默病、认知功能障碍、痴呆症、焦虑症（广泛性焦虑症、恐慌症、强迫症、社交焦虑症、创伤后应激障碍、特定恐惧症、急性应激障碍等）、抑郁症、药物成瘾、痉挛、震颤和睡眠障碍等疾病的预防或治疗方面具有用处。
• GLYCINE TRANSPORTER INHIBITOR
  申请人：Taisho Pharmaceutical Co., Ltd.

  公开号：EP2409976A1

  公开（公告）日：2012-01-25

  The present invention aims to provide novel compounds of formula [I] or pharmaceutically acceptable salts thereof that are based on a glycine uptake inhibiting action and which are useful in the prevention or treatment of such diseases as schizophrenia, Alzheimer's disease, cognitive dysfunction, dementia, anxiety disorders (generalized anxiety disorder, panic disorder, obsessive-compulsory disorder, social anxiety disorder, posttraumatic stress disorder, specific phobia, acute stress disorder, etc.), depression, drug addiction, spasm, tremor, and sleep disorder:

  本发明旨在提供基于甘氨酸摄取抑制作用的新型式[I]化合物或其药学上可接受的盐，这些化合物可用于预防或治疗精神分裂症、阿尔茨海默病、认知功能障碍、痴呆症、焦虑症（广泛性焦虑症、恐慌症、强迫症、社交焦虑症、创伤后应激障碍、特殊恐惧症、急性应激障碍等）等疾病。抑郁症、药物成瘾、痉挛、震颤和睡眠障碍）：
• METHODS OF TREATING ERYTHROPOIETIC PROTOPORPHYRIA, X-LINKED PROTOPORPHYRIA, OR CONGENITAL ERYTHROPOIETIC PORPHYRIA WITH GLYCINE TRANSPORT INHIBITORS
  申请人：Disc Medicine, Inc.

  公开号：US20210283129A1

  公开（公告）日：2021-09-16

  The present embodiments are directed to methods of using glycine transporter inhibitors, such as GlyT1 inhibitors, or pharmaceutically acceptable salts, solvates or prodrugs thereof, or pharmaceutical compositions thereof, for preventing or treating erythropoietic protoporphyria (EPP), X-linked protoporphyria (XLPP), and/or congenital erythropoietic porphyria (CEP), and related syndromes thereof.
• US8623898B2
  申请人：——

  公开号：US8623898B2

  公开（公告）日：2014-01-07