N-(4-bromophenyl)-D-phenylalaninamide | 928322-34-3

• 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: N-(4-bromophenyl)-D-phenylalaninamide
• 英文别名: (2R)-2-amino-N-(4-bromophenyl)-3-phenylpropanamide
• CAS: 928322-34-3
• 化学式: C₁₅H₁₅BrN₂O
• 分子量: 319.201
• InChiKey: SYARKJDDXKEXND-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(4-bromophenyl)-D-phenylalaninamide 在 1-羟基苯并三唑 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成
  参考文献：
  名称：

  Terminal functionalized thiourea-containing dipeptides as multidrug-resistance reversers that target 20S proteasome and cell proliferation

  摘要：

  A series of inhibitors of 20S proteasome based on terminal functionalized dipeptide derivatives containing the thiourea moiety were synthesized and evaluated for inhibition of 20S proteasome and the effects of multidrug-resistance reversers. These compounds exhibited significant selectivity to the 05 subunit of the human 20S proteasome with IC50 values at submicromolar concentrations. A docking study of the most active compound 6i revealed key interactions between 6i and the active site of the 20S proteasome in which the thiourea moiety and a nitro group were important for improving activity. In particular, compound 6i appeared to be the most potent compound against the NCI-H460 cell line, and displayed similar efficiency in drug-sensitive versus drug-resistant cancer cell lines, at least partly, by inhibition of the activity of 20S proteasome and induce apoptosis. In addition, 6i-induced apoptosis was significantly facilitated in NCI-H460/DOX cells that had been pretreated with inhibitors of P-gp. Mechanistically, compound 6i might trigger apoptotic signalling pathway. Thus, we conclude that dipeptide derivatives containing the thiourea moiety may be the potential inhibitors of proteasome with the ability to reverse multidrug resistance. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.11.024
• 作为产物：
  描述：

  (R)-tert-butyl (1-((4-bromophenyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-(4-bromophenyl)-D-phenylalaninamide
  参考文献：
  名称：

  Terminal functionalized thiourea-containing dipeptides as multidrug-resistance reversers that target 20S proteasome and cell proliferation

  摘要：

  A series of inhibitors of 20S proteasome based on terminal functionalized dipeptide derivatives containing the thiourea moiety were synthesized and evaluated for inhibition of 20S proteasome and the effects of multidrug-resistance reversers. These compounds exhibited significant selectivity to the 05 subunit of the human 20S proteasome with IC50 values at submicromolar concentrations. A docking study of the most active compound 6i revealed key interactions between 6i and the active site of the 20S proteasome in which the thiourea moiety and a nitro group were important for improving activity. In particular, compound 6i appeared to be the most potent compound against the NCI-H460 cell line, and displayed similar efficiency in drug-sensitive versus drug-resistant cancer cell lines, at least partly, by inhibition of the activity of 20S proteasome and induce apoptosis. In addition, 6i-induced apoptosis was significantly facilitated in NCI-H460/DOX cells that had been pretreated with inhibitors of P-gp. Mechanistically, compound 6i might trigger apoptotic signalling pathway. Thus, we conclude that dipeptide derivatives containing the thiourea moiety may be the potential inhibitors of proteasome with the ability to reverse multidrug resistance. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.11.024

文献信息

• AMIDE DERIVATIVES AS ROCK INHIBITORS
  申请人：Sawada Kouzo

  公开号：US20090105231A1

  公开（公告）日：2009-04-23

  This invention relates to novel amide derivatives and salts thereof. More particularly, it relates to novel amide derivatives and salts thereof which act as a ROCK inhibitor, to a pharmaceutical composition comprising the same and to a method of using the same therapeutically in the treatment and/or prevention of ROCK-related disease.

  本发明涉及新型酰胺衍生物及其盐。更具体地说，涉及一种作为ROCK抑制剂的新型酰胺衍生物及其盐，以及包含其的制药组合物和在治疗和/或预防ROCK相关疾病方面的治疗方法。
• Amide derivatives as rock inhibitors
  申请人：Astellas Pharma Inc.

  公开号：US08211919B2

  公开（公告）日：2012-07-03

  This invention relates to novel amide derivatives and salts thereof. More particularly, it relates to novel amide derivatives and salts thereof which act as a ROCK inhibitor, to a pharmaceutical composition comprising the same and to a method of using the same therapeutically in the treatment and/or prevention of ROCK-related disease.

  本发明涉及新型酰胺衍生物及其盐。更具体地说，涉及一种作为ROCK抑制剂的新型酰胺衍生物及其盐，以及包含其的制药组合物，并且涉及一种在治疗和/或预防ROCK相关疾病方面治疗的方法。
• WO2007/26920
  申请人：——

  公开号：——

  公开（公告）日：——
• US8211919B2
  申请人：——

  公开号：US8211919B2

  公开（公告）日：2012-07-03
• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSES
  申请人：ASTELLAS PHARMA INC

  公开号：WO2007026920A2

  公开（公告）日：2007-03-08

  [EN] This invention relates to novel amide derivatives and salts thereof. More particularly, it relates to novel amide derivatives and salts thereof which act as a ROCK inhibitor, to a pharmaceutical composition comprising the same and to a method of using the same therapeutically in the treatment and/or prevention of ROCK-related disease.
  [FR] La présente invention concerne de nouveaux dérivés d'amide et les sels de ces derniers et concerne plus particulièrement de nouveaux dérivés d'amide ainsi que leurs sels qui agissent en tant qu'inhibiteur de ROCK, une composition pharmaceutique comprenant ces derniers et une méthode d'utilisation de cette dernière à des fins thérapeutiques dans le traitement et/ou la prévention des maladies associées à ROCK.