1-Ethyl-5'-hydroxy-3'-methyl-5-phenyl-7-(trifluoromethyl)spiro[1,5-benzodiazepine-3,1'-indane]-2,4-dione | 1329991-22-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-Ethyl-5'-hydroxy-3'-methyl-5-phenyl-7-(trifluoromethyl)spiro[1,5-benzodiazepine-3,1'-indane]-2,4-dione
• 英文别名: 1'-ethyl-6-hydroxy-1-methyl-5'-phenyl-7'-(trifluoromethyl)spiro[1,2-dihydroindene-3,3'-1,5-benzodiazepine]-2',4'-dione
• CAS: 1329991-22-1
• 化学式: C₂₇H₂₃F₃N₂O₃
• 分子量: 480.486
• InChiKey: JSGUOWPTTFDGBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  35
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1'-Ethyl-5'-phenyl-6-phenylmethoxy-7'-(trifluoromethyl)spiro[1,2-dihydroindene-3,3'-1,5-benzodiazepine]-2',4'-dione 在 chromium(VI) oxide 、 palladium on activated charcoal 、 氢气 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 1-Ethyl-5'-hydroxy-3'-methyl-5-phenyl-7-(trifluoromethyl)spiro[1,5-benzodiazepine-3,1'-indane]-2,4-dione
  参考文献：
  名称：

  Optimization of a 1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione series of HIV capsid assembly inhibitors 1: Addressing configurational instability through scaffold modification

  摘要：

  The optimization of a 1,5-dihydrobenzo[b][1,4] diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly that possess a labile stereocenter at C3 is described. Quaternization of the C3 position of compound 1 in order to prevent racemization gave compound 2, which was inactive in our capsid disassembly assay. A likely explanation for this finding was revealed by in silico analysis predicting a dramatic increase in energy of the bioactive conformation upon quaternization of the C3 position. Replacement of the C3 of the diazepine ring with a nitrogen atom to give the 1,5-dihydro-benzo[f][1,3,5]-triazepine-2,4-dione analog 4 was well tolerated. Introduction of a rigid spirocyclic system at the C3 position gave configurationally stable 1,5-dihydrobenzo[b][1,4] diazepine-2,4-dione analog 5, which was able to access the bioactive conformation without a severe energetic penalty and inhibit capsid assembly. Preliminary structure-activity relationships (SAR) and X-ray crystallographic data show that knowledge from the 1,5-dihydrobenzo[ b][1,4] diazepine-2,4-dione series of inhibitors of HIV-1 capsid assembly can be transferred to these new scaffolds. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.073

文献信息

• [EN] DERIVATIVES OF L-PLIENYL-1.5-DILIYDIO-BENZO[B] [1.4]DIAZEPINE-2.4-DIONE AS INHIBITORS OF HIV REPLICATION<br/>[FR] DÉRIVÉS DE 1-PHÉNYL-1,5-DIHYDRO-BENZO[B] [1.4]DIAZÉPINE-2.4-DIONE EN TANT QU'INHIBITEURS DE LA RÉPLICATION DU VIH
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2011100838A9

  公开（公告）日：2012-12-27
• Derivatives of 1-Phenyl-1,5-Dihydro-Benzo[B] [1,4]Diazepine-2,4-Dione as Inhibitors of HIV Replication
  申请人：Simoneau Bruno

  公开号：US20130150350A1

  公开（公告）日：2013-06-13

  Compounds of formula (I) wherein m, R 1 , R 2 , R 3 , X and Y are defined herein, are useful as inhibitors of HIV replication.
• [EN] DERIVATIVES OF 1-PHENYL-1,5-DIHYDRO-BENZO[B] [1.4]DIAZEPINE-2.4-DIONE AS INHIBITORS OF HIV REPLICATION<br/>[FR] DÉRIVÉS DE 1-PHÉNYL-1,5-DIHYDRO-BENZO[B] [1.4]DIAZÉPINE-2.4-DIONE EN TANT QU'INHIBITEURS DE LA RÉPLICATION DU VIH
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2011100838A1

  公开（公告）日：2011-08-25

  Compounds of formula (I) wherein m, R1, R2, R3, X and Y are defined herein, are useful as inhibitors of HIV replication.