4-(2-chlorophenyl)-2-[2-(4-methylphenyl)ethyl]-9-methyl-6H-thieno-[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻烯杂卓类
• 英文名称: 4-(2-chlorophenyl)-2-[2-(4-methylphenyl)ethyl]-9-methyl-6H-thieno-[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine
• 英文别名: 4-(2-chlorophenyl)-2-[2-(4-methylphenyl)ethyl]9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine；7-(2-Chlorophenyl)-13-methyl-4-[2-(4-methylphenyl)ethyl]-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaene
• 化学式: C₂₄H₂₁ClN₄S
• 分子量: 432.977
• InChiKey: UGSHFXMQGVBNJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  71.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(2-chlorophenyl)-2-[2-(4-methylphenyl)ethyl]-9-methyl-6H-thieno-[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine 生成 (2-chlorophenyl)-[2-[3-[(dimethylamino)methyl]-5-methyl-1,2,4-triazol-4-yl]-5-[2-(4-methylphenyl)ethyl]thiophen-3-yl]methanone
  参考文献：
  名称：

  MORIVAKI, MINORU;NAKADZIMA, TORU;TEHRASAVA, MITIO;TAXARA, TEHTSUXARU

  摘要：

  DOI：
• 作为产物：
  描述：

  4-对甲苯基丁酸 在 2,2,6,6-tetramethyl-piperidine-N-oxyl 、 sodium hypochlorite 、 sodium tetrahydroborate 、 tetraphosphorus decasulfide 、 三氟化硼乙醚 、 氨 、 碳酸氢钠 、 sulfur 、 一水合肼 、 溶剂黄146 、 三乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 、 异丙醇 、 甲苯 为溶剂， 反应 39.5h， 生成 4-(2-chlorophenyl)-2-[2-(4-methylphenyl)ethyl]-9-methyl-6H-thieno-[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine
  参考文献：
  名称：

  Structural optimization of 4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-[1,2,4]triazolo[4,3-a][1,4]diazepines as antagonists for platelet activating factor: pharmacological contribution of substituents at the 2- and 6-positions of a condensed ring system

  摘要：

  A series of 4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine derivatives bearing substituents at the 2- and 6-positions were synthesized, and evaluated in vitro for their inhibitory activity on rabbit platelet aggregation induced by platelet activating factor (PAF) and in vivo for their preventing effect on PAF-induced mortality in mice. The length of alkyl or arylalkyl side chain at the 2-position was responsible for enhancing the affinity for the PAF receptor. The simultaneous substitution at both the 2- and 6-positions resulted in a successful separation of the affinity for the PAF receptor from that for the benzodiazepine (BZ) receptor. Thus, (+/-)-4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (Y-24180) was confirmed to be a specific antagonist for the PAF receptor and is currently under clinical trials.

  DOI：

  10.1016/0223-5234(96)85877-6

文献信息

• PAF-antagonistic thienotriazolodiazepine compounds and pharmaceutical uses thereof
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：EP0268242A1

  公开（公告）日：1988-05-25

  A thienotriazolodiazepine compound of the general formula (I): wherein each symbol is as defined in the specification and a pharmaceutically acceptable acid addition salt thereof, and pharmaceutical uses thereof. Said compounds exhibit PAF-antagonistic activity and are useful for the prevention or treatment of various PAF-induced diseases.

  通式(I)的噻吩三唑二氮杂卓化合物： 其中各符号如说明书中所定义及其药学上可接受的酸加成盐，以及它们的药物用途。 所述化合物具有 PAF 拮抗活性，可用于预防或治疗各种 PAF 引起的疾病。
• MORIVAKI, MINORU;NAKADZIMA, TORU;TEHRASAVA, MITIO;TAXARA, TEHTSUXARU
  作者：MORIVAKI, MINORU、NAKADZIMA, TORU、TEHRASAVA, MITIO、TAXARA, TEHTSUXARU

  DOI：——

  日期：——
• EP0268242B1
  申请人：——

  公开号：EP0268242B1

  公开（公告）日：1992-03-18
• US4820703A
  申请人：——

  公开号：US4820703A

  公开（公告）日：1989-04-11
• Structural optimization of 4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]-[1,2,4]triazolo[4,3-a][1,4]diazepines as antagonists for platelet activating factor: pharmacological contribution of substituents at the 2- and 6-positions of a condensed ring system
  作者：Y Kawakami、H Kitani、S Yuasa、M Abe、M Moriwaki、M Kagoshima、M Terasawa、T Tahara

  DOI：10.1016/0223-5234(96)85877-6

  日期：1996.1

  A series of 4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine derivatives bearing substituents at the 2- and 6-positions were synthesized, and evaluated in vitro for their inhibitory activity on rabbit platelet aggregation induced by platelet activating factor (PAF) and in vivo for their preventing effect on PAF-induced mortality in mice. The length of alkyl or arylalkyl side chain at the 2-position was responsible for enhancing the affinity for the PAF receptor. The simultaneous substitution at both the 2- and 6-positions resulted in a successful separation of the affinity for the PAF receptor from that for the benzodiazepine (BZ) receptor. Thus, (+/-)-4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (Y-24180) was confirmed to be a specific antagonist for the PAF receptor and is currently under clinical trials.