(RS)-6-(3,5-bis-trifluoromethyl-benzyl)-4-(3,4-dichloro-benzyl)-3-(2-morpholin-4-yl-ethyl)-7,8-dihydro-6H-1,2,3a,6-tetraaza-azulen-5-one | 376595-20-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (RS)-6-(3,5-bis-trifluoromethyl-benzyl)-4-(3,4-dichloro-benzyl)-3-(2-morpholin-4-yl-ethyl)-7,8-dihydro-6H-1,2,3a,6-tetraaza-azulen-5-one
• 英文别名: 7-[[3,5-bis(trifluoromethyl)phenyl]methyl]-5-[(3,4-dichlorophenyl)methyl]-3-(2-morpholin-4-ylethyl)-8,9-dihydro-5H-[1,2,4]triazolo[4,3-d][1,4]diazepin-6-one
• CAS: 376595-20-9
• 化学式: C₂₈H₂₇Cl₂F₆N₅O₂
• 分子量: 650.451
• InChiKey: BMWMFZCWYHPVRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  43
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  63.5
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (RS)-1-(3,5-bis-trifluoromethyl-benzyl)-3-(3,4-dichloro-benzyl)-5-thioxo-[1,4]diazepan-2-one 、 正丁醇 、 3-吗啉-4-丙酸肼 在 水 、 乙酸乙酯 、 magnesium sulfate 、 SiO2 、 methanol-dichloromethane 作用下， 反应 16.0h， 以to yield 77 mg (59.2%) of the title compound as a light yellow solid的产率得到(RS)-6-(3,5-bis-trifluoromethyl-benzyl)-4-(3,4-dichloro-benzyl)-3-(2-morpholin-4-yl-ethyl)-7,8-dihydro-6H-1,2,3a,6-tetraaza-azulen-5-one
  参考文献：
  名称：

  Diazapane derivatives useful as antagonists of neurokinin 1 receptor and methods for their formation

  摘要：

  本发明涉及公式化合物，其中：R1、R2独立地为芳基或杂芳基，其中杂芳基含有1或2个从N、O或S中选择的杂原子，且所述芳基或杂芳基上可选择性地取代1到3个取代基，所述取代基独立地为卤素、CF3、低烷氧基或低烷基；R3为氢、低烷基、-(CH2)nN(R)2、-(CH2)n-杂芳基或为-(CH2)n-非芳杂环，所述杂环上可选择性地取代卤素、CF3、低烷氧基或低烷基；R4为═O、═N(CH2)nCH3或═N(CH2)nN(R)2；R3和R4可与它们结合的N和C原子一起形成—CR5═N—N═基团；R5为氢、-(CH2)nN(R)2、-(CH2)n-杂芳基或为-(CH2)n-非芳杂环，所述杂环上可选择性地取代卤素、CF3、低烷氧基或低烷基；R为氢或低烷基；n为0、1、2或3；以及其药物可接受的酸盐和对映体形式。所述化合物在与NK-1受体相关的疾病的治疗中有用。

  公开号：

  US06452001B2

文献信息

• 1,4-DIAZEPAN-2,5-DIONE DERIVATIVES AND THEIR USE AS NK-1 RECEPTOR ANTAGONISTS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1296961A1

  公开（公告）日：2003-04-02
• US6452001B2
  申请人：——

  公开号：US6452001B2

  公开（公告）日：2002-09-17
• [EN] 1,4-DIAZEPAN-2,5-DIONE DERIVATIVES AND THEIR USE AS NK-1 RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE LA 1,4-DIAZEPAN-2,5-DIONE ET LEUR UTILISATION COMME ANTAGONISTES DU RECEPTEUR DE LA NK-1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2001090083A1

  公开（公告）日：2001-11-29

  The invention relates to compounds of general formula (I) wherein R1, R2 are independently from each other aryl or heteroaryl, wherein the heteroaryl group contains one or two heteroatoms, selected from N, O or S, and wherein the aryl or heteroaryl groups are optionally substituted by 1 to 3 substituents, which are independently from each other halogen, CF¿3?, lower alkoxy or lower alykl; R?3¿ is hydrogen, lower alkyl, -(CH¿2?)nN(R)2, -(CH2)n-heteroaryl or is a -(CH2)n-non aromatic heterocycle, which heterocycles are optionally substituted by halogen, CF3, lower alkoxy or lower alkyl; R?4¿ is =O, =N(CH¿2?)nCH3 or =N(CH2)nN(R)2; R?3 and R4¿ may be together with the N and C atoms to which they are attached the group -CR5=N-N=; R5 is hydrogen, -(CH¿2?)nN(R)2, -(CH2)n-heteroaryl or is a -(CH2)n-non aromatic heterocycle, which heterocycles are optionally substituted by halogen, CF3, lower alkoxy or lower alkyl; R is hydrogen or lower alkyl; n is 0, 1, 2 or 3; and pharmaceutically acceptable acid addition salts and enantiomeric forms thereof. The compounds are useful in the treatment of diseases, related to the NK-1 receptor.