4-chloro-2-methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-chloro-2-methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine
• 英文别名: 4-chloro-2-methylsulfanyl-7-(3-trifluoromethylpyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine；4-Chloro-2-methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine；4-chloro-2-methylsulfanyl-7-[3-(trifluoromethyl)pyridin-2-yl]-5,6,8,9-tetrahydropyrimido[4,5-d]azepine
• 化学式: C₁₅H₁₄ClF₃N₄S
• 分子量: 374.817
• InChiKey: XRQNLXNXIATOAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  67.2
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-chloro-2-methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine 、 对三氟甲基苯胺 在 碳酸氢钠 、 乙酸乙酯 、 magnesium sulfate 作用下， 以 正丁醇 为溶剂， 反应 0.5h， 以to give the title compound (950 mg, 86%)的产率得到Example 52
  参考文献：
  名称：

  Tetrahydro-pyrimidoazepines as modulators of TRPV1

  摘要：

  本文描述了某些四氢嘧啶并氮杂环化合物，可用作TRPV1调节剂。这些化合物可用于制备药物组合物并用于治疗由TRPV1介导的疾病状态、紊乱和情况的方法。因此，这些化合物可用于治疗疼痛、瘙痒、咳嗽、哮喘或炎症性肠病等疾病。

  公开号：

  US08673895B2
• 作为产物：
  描述：

  在 三氯氧磷 作用下， 以 乙腈 为溶剂， 生成 4-chloro-2-methylsulfanyl-7-(3-trifluoromethyl-pyridin-2-yl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepine
  参考文献：
  名称：

  1,2-Diamino-ethane-substituted-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepines as TRPV1 antagonists with improved properties

  摘要：

  Based upon a previously reported lead compound 1, a series of 1,2-diamino-ethane-substituted-6,7,8,9-tetrahydro-5H-pyrimido[4,5-d]azepines were synthesized and evaluated for improved physiochemical and pharmacokinetic properties while maintaining TRPV1 antagonist activity. Structure-activity relationship studies directed toward improving the aqueous solubility (pH 2 and fasted-state simulated intestinal fluid (SIF)) and rat pharmacokinetics led to the discovery of compound 13. Aqueous solubility of compound 13 (pH 2 = > 237 mu g/mL and SIF = 11 mu g/mL) was significantly improved over compound 1 (pH 2 = 5 mu g/mL and SIF = 0.5 mu g/mL). In addition, compound 13 afforded improved rat pharmacokinetics (CL = 0.7 L/kg/h) compared to compound 1 (CL = 3.1 L/kg/h). Compound 13 was orally bioavailable and afforded a significant reversal of carrageenan-induced thermal hyperalgesia at 5 and 30 mg/kg in rats. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.006

文献信息

• TETRAHYDRO-PYRIMIDOAZEPINES AS MODULATORS OF TRPV1
  申请人：Janssen Pharmaceutica NV

  公开号：US20140135311A1

  公开（公告）日：2014-05-15

  Certain tetrahydro-pyrimidoazepine compounds are described, which are useful as TRPV1 modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by TRPV1. Thus, the compounds may be administered to treat, e.g., pain, itch, cough, asthma, or inflammatory bowel disease.

  本文描述了某些四氢嘧啶并氮杂莫尔环化合物，它们可用作TRPV1调节剂。这些化合物可用于制备药物组合物和治疗TRPV1介导的疾病状态、障碍和情况的方法。因此，这些化合物可用于治疗疼痛、瘙痒、咳嗽、哮喘或炎症性肠病等疾病。
• 6,7,8,9-TETRAHYDRO-5H-PYRIMIDO[4,5-D]AZEPIN-4-YL]-AMINE DERIVATIVES AS MODULATORS OF TRPV1 FOR THE TREATMENT OF PAIN
  申请人：Janssen Pharmaceutica N.V.

  公开号：EP2024368B1

  公开（公告）日：2014-04-30
• HIGH EFFICIENCY SOLUTION POLYMERIZATION PROCESS
  申请人：DOW GLOBAL TECHNOLOGIES INC.

  公开号：EP2024400A2

  公开（公告）日：2009-02-18
• US8673895B2
  申请人：——

  公开号：US8673895B2

  公开（公告）日：2014-03-18
• US9422293B2
  申请人：——

  公开号：US9422293B2

  公开（公告）日：2016-08-23