(2S,2'S)-di-tert-butyl 2,2'-(([1,1'-biphenyl]-4,4'-diylbis(azanediyl))bis(carbonyl))bis(pyrrolidine-1-carboxylate) | 1512624-36-0

• 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: (2S,2'S)-di-tert-butyl 2,2'-(([1,1'-biphenyl]-4,4'-diylbis(azanediyl))bis(carbonyl))bis(pyrrolidine-1-carboxylate)
• 英文别名: tert-butyl (2S)-2-[[4-[4-[[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carbonyl]amino]phenyl]phenyl]carbamoyl]pyrrolidine-1-carboxylate
• CAS: 1512624-36-0
• 化学式: C₃₂H₄₂N₄O₆
• 分子量: 578.709
• InChiKey: IBJCUKODTIDUQC-UIOOFZCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  42
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,2'S)-di-tert-butyl 2,2'-(([1,1'-biphenyl]-4,4'-diylbis(azanediyl))bis(carbonyl))bis(pyrrolidine-1-carboxylate) 在 1,2-二氯乙烷 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.25h， 生成 (2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]-N-[4-[4-[[(2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidine-2-carbonyl]amino]phenyl]phenyl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Potent Hepatitis C Virus NS5A Inhibitors Containing a Benzidine Core

  摘要：

  Here we report the discovery of a series of potent hepatitis C virus (HCV) NS5A inhibitors based on the benzidine prolinamide backbone. Taking a simple synthetic route, we developed a novel inhibitor structure, which allows easy modification, and through optimization of the capping group, we identified compound 6 with highly potent anti-HCV activity. Compound 6 is nontoxic and is anticipated to be an effective HCV drug candidate.

  DOI：

  10.1021/ml4003293
• 作为产物：
  描述：

  BOC-L-脯氨酸 、 联苯胺 在 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以95%的产率得到(2S,2'S)-di-tert-butyl 2,2'-(([1,1'-biphenyl]-4,4'-diylbis(azanediyl))bis(carbonyl))bis(pyrrolidine-1-carboxylate)
  参考文献：
  名称：

  通过立体化学交换和拟肽方法扩展抗 HCV NS5A 抑制剂的化学空间

  摘要：

  在这里，我们报告了一系列具有对称联苯胺 l-脯氨酰胺骨架和不同封端基团的强效抗 HCV 药物，包括天然和非天然缬氨酸和亮氨酸氨基酸的烷基/芳基氨基甲酸酯。研究了所有化合物在基因型 1b 的 HCV 复制子测定中的抑制活性。这些新化合物具有市售 NS5A 抑制剂的一些化学和临床属性。具有非天然封端残基和氨基甲酸乙酯和异丁酯的化合物 5 和 6 的 EC50 值在皮摩尔范围内，具有低毒性和几个数量级的选择性指数。这些发现扩大了通过采用非天然氨基酸、缬氨酸以外的氨基酸和甲基以外的氨基甲酸酯作为封端基团来发现NS5A抑制剂的化学空间。

  DOI：

  10.1002/ardp.201800017

文献信息

• Expanding the chemical space of anti-HCV NS5A inhibitors by stereochemical exchange and peptidomimetic approaches
  作者：Triveena M. Ramsis、Shereen E. Abdel Karim、Niki Vassilaki、Efseveia Frakolaki、Ahmed A. M. Kamal、Grigoris Zoidis、Nermin S. Ahmed、Ashraf H. Abadi

  DOI：10.1002/ardp.201800017

  日期：2018.7

  Here we report a series of potent anti‐HCV agents bearing a symmetrical benzidine l‐prolinamide backbone with different capping groups including alkyl/aryl carbamates of natural and unnatural valine and leucine amino acids. All compounds were investigated for their inhibitory activity in an HCV replicon assay on genotype 1b. The novel compounds share some chemical and clinical attributes of commercially

  在这里，我们报告了一系列具有对称联苯胺 l-脯氨酰胺骨架和不同封端基团的强效抗 HCV 药物，包括天然和非天然缬氨酸和亮氨酸氨基酸的烷基/芳基氨基甲酸酯。研究了所有化合物在基因型 1b 的 HCV 复制子测定中的抑制活性。这些新化合物具有市售 NS5A 抑制剂的一些化学和临床属性。具有非天然封端残基和氨基甲酸乙酯和异丁酯的化合物 5 和 6 的 EC50 值在皮摩尔范围内，具有低毒性和几个数量级的选择性指数。这些发现扩大了通过采用非天然氨基酸、缬氨酸以外的氨基酸和甲基以外的氨基甲酸酯作为封端基团来发现NS5A抑制剂的化学空间。
• 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。
• Synthesis and biological evaluation of novel bis-aromatic amides as novel PTP1B inhibitors
  作者：Wen-Long Wang、Chao Huang、Li-Xin Gao、Chun-Lan Tang、Jun-Qing Wang、Min-Chen Wu、Li Sheng、Hai-Jun Chen、Fa-Jun Nan、Jing-Ya Li、Jia Li、Bainian Feng

  DOI：10.1016/j.bmcl.2014.03.015

  日期：2014.4

  A series of bis-aromatic amides was designed, synthesized, and evaluated as a new class of inhibitors with IC50 values in the micromolar range against protein tyrosine phosphatase 1B (PTP1B). Among them, compound 15 displayed an IC50 value of 2.34 +/- 0.08 mu M with 5-fold preference over TCPTP. More importantly, the treatment of CHO/HIR cells with compound 15 resulted in increased phosphorylation of insulin receptor (IR), which suggested extensive cellular activity of compound 15. These results provided novel lead compounds for the design of inhibitors of PTP1B as well as other PTPs. (C) 2014 Elsevier Ltd. All rights reserved.
• 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.
• US9598362B2
  申请人：——

  公开号：US9598362B2

  公开（公告）日：2017-03-21