dimethyl (1R,1'R)-2,2'-((2S,2'S)-2,2'-(9,9-difluoro-9H-fluorene-2,7-diyl)bis(azanediyl)bis(oxomethylene)bis(pyrrolidine-2,1-diyl))bis(2-oxo-1-phenylethane-2,1-diyl)dicarbamate

• 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: dimethyl (1R,1'R)-2,2'-((2S,2'S)-2,2'-(9,9-difluoro-9H-fluorene-2,7-diyl)bis(azanediyl)bis(oxomethylene)bis(pyrrolidine-2,1-diyl))bis(2-oxo-1-phenylethane-2,1-diyl)dicarbamate
• 英文别名: dimethyl ((1R,1'R)-((2S,2'S)-2,2'-(((9,9-difluoro-9H-fluorene-2,7-diyl)bis(azandiyl))bis(carbonyl))bis(pyrrolidine-2,1-diyl))bis(2-oxo-1-phenylethane-2,1-diyl))dicarbamate；methyl N-[(1R)-2-[(2S)-2-[[9,9-difluoro-7-[[(2S)-1-[(2R)-2-(methoxycarbonylamino)-2-phenylacetyl]pyrrolidine-2-carbonyl]amino]fluoren-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxo-1-phenylethyl]carbamate
• 化学式: C₄₃H₄₂F₂N₆O₈
• 分子量: 808.839
• InChiKey: CCUVMKJCIIRLKV-CLLHQPRTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  59
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  176
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  左旋苯甘氨酸 在 sodium carbonate 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 4.57h， 生成 dimethyl (1R,1'R)-2,2'-((2S,2'S)-2,2'-(9,9-difluoro-9H-fluorene-2,7-diyl)bis(azanediyl)bis(oxomethylene)bis(pyrrolidine-2,1-diyl))bis(2-oxo-1-phenylethane-2,1-diyl)dicarbamate
  参考文献：
  名称：

  Novel benzidine and diaminofluorene prolinamide derivatives as potent hepatitis C virus NS5A inhibitors

  摘要：

  Our study describes the discovery of a series of highly potent hepatitis C virus (HCV) NS5A inhibitors based on symmetrical prolinamide derivatives of benzidine and diaminofluorene. Through modification of benzidine, L-proline, and diaminofluorene derivatives, we developed novel inhibitor structures, which allowed us to establish a library of potent HCV NS5A inhibitors. After optimizing the benzidine prolinamide backbone, we identified inhibitors embedding meta-substituted benzidine core structures that exhibited the most potent anti-HCV activities. Furthermore, through a battery of studies including hERG ligand binding assay, CYP450 binding assay, rat plasma stability test, human liver microsomal stability test, and pharmacokinetic studies, the identified compounds 24, 26, 27, 42, and 43 are found to be nontoxic, and are expected to be effective therapeutic anti-HCV agents. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.033

文献信息

• BENZIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING BENZIDINE DERIVATIVE FOR TREATING LIVER DISEASE CAUSED BY HEPATITIS C VIRUS
  申请人：SEOUL NATIONAL UNIVERSITY R&DB FOUNDATION

  公开号：US20160031810A1

  公开（公告）日：2016-02-04

  The disclosed compounds have antiviral activity against C-type virus, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient for preventing or treating liver disease caused by hepatitis C virus. The benzidine derivative according to the present invention has excellent antiviral activity against hepatitis C virus and exhibits excellent medicinal activity in the living body, and thus the pharmaceutical composition containing the same as an active ingredient can be useful as a pharmaceutical composition for preventing or treating liver disease, such as acute hepatitis C, chronic hepatitis C, cirrhosis, or hepatocellular carcinoma, caused by C-type virus.

  揭示的化合物对C型病毒具有抗病毒活性，包括其光学异构体、药学上可接受的盐、制备方法以及含有其作为活性成分的药物组合物，用于预防或治疗由丙型肝炎病毒引起的肝病。根据本发明的苯胺衍生物对丙型肝炎病毒具有出色的抗病毒活性，在活体内表现出优秀的药用活性，因此含有其作为活性成分的药物组合物可作为用于预防或治疗由C型病毒引起的肝病，如急性丙型肝炎、慢性丙型肝炎、肝硬化或肝细胞癌等的药物组合物。
• US9598362B2
  申请人：——

  公开号：US9598362B2

  公开（公告）日：2017-03-21
• Novel benzidine and diaminofluorene prolinamide derivatives as potent hepatitis C virus NS5A inhibitors
  作者：Il Hak Bae、Hee Sun Kim、Youngsu You、Chieyeon Chough、Weonu Choe、Min Kyung Seon、Seung Gi Lee、Gyochang Keum、Sung Key Jang、B. Moon Kim

  DOI：10.1016/j.ejmech.2015.06.033

  日期：2015.8

  Our study describes the discovery of a series of highly potent hepatitis C virus (HCV) NS5A inhibitors based on symmetrical prolinamide derivatives of benzidine and diaminofluorene. Through modification of benzidine, L-proline, and diaminofluorene derivatives, we developed novel inhibitor structures, which allowed us to establish a library of potent HCV NS5A inhibitors. After optimizing the benzidine prolinamide backbone, we identified inhibitors embedding meta-substituted benzidine core structures that exhibited the most potent anti-HCV activities. Furthermore, through a battery of studies including hERG ligand binding assay, CYP450 binding assay, rat plasma stability test, human liver microsomal stability test, and pharmacokinetic studies, the identified compounds 24, 26, 27, 42, and 43 are found to be nontoxic, and are expected to be effective therapeutic anti-HCV agents. (C) 2015 Elsevier Masson SAS. All rights reserved.