硼替佐米杂质61 | 789472-91-9

• 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
• 中文名称: 硼替佐米杂质61
• 英文名称: N-{(1S)-3-methyl-1-[(3aS,4S,6S,7aS)-3a,5,5-trimethylhexahydro-4,6-methano-1,3,2-benzodioxaborol-2-yl]butyl}phenylalanine amide
• 英文别名: (S)-2-Amino-N-((R)-3-methyl-1-((3aS,4S,6S,7aR)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)butyl)-3-phenylpropanamide；(2S)-2-amino-N-[(1R)-3-methyl-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]butyl]-3-phenylpropanamide
• CAS: 789472-91-9
• 化学式: C₂₄H₃₇BN₂O₃
• 分子量: 412.38
• InChiKey: XQVVQXGUJAMKFX-NNQKNUJYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  73.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  -20°C

反应信息

• 作为反应物：
  描述：

  硼替佐米杂质61 在 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 硼替佐米
  参考文献：
  名称：

  Further characterization of a putative serine protease contributing to the γ-secretase cleavage of β-amyloid precursor protein

  摘要：

  The 3-alkoxy-7-amino-4-chloro-isocoumarins JLK-6 and JLK-2 have been shown to markedly reduce the production of Amyloid beta-peptide (A beta) by Amyloid-beta Precursor Protein (APP) expressing HEK293 cells by affecting the gamma-secretase cleavage of APP, with no effect on the cleavage of the Notch receptor. This suggested that these compounds do not directly inhibit the presenilin-dependent gamma-secretase complex but more likely interfere with an upstream target involved in gamma-secretase-associated pathway. The mechanism of action of these compounds is unknown and there are high fundamental and therapeutical interests to unravel their target. Isocoumarin compounds were previously shown to behave as potent mechanism-based irreversible inhibitors of serine proteases, suggesting that the JLK-directed target could belong to such enzyme family. To get further insight into structure-activity relationships and to develop more potent isocoumarin derivatives, we have synthesized and evaluated a series of isocoumarin analogues with modifications at positions 3, 4 and 7. In particular, the 7-amino group was substituted with either acyl, urethane, alkyl or aryl groups, which could represent additional interaction sites. Altogether, the results highlighted the essential integrity of the 3-alkoxy-7-amino-4-chloro-isocoumarin scaffold for A beta-lowering activity and supported the involvement of a seri ne protease, or may be more generally, a serine hydrolase. The newly reported 7-N-alkyl series produced the most active compounds with an IC50 between 10 and 30 mu M. Finally, we also explored peptide boronates, a series of reversible serine protease inhibitors, previously shown to also lower cellular A beta production. The presented data suggested they could act on the same target or interfere with the same pathway as isocoumarins derivatives. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.045
• 作为产物：
  描述：

  博特佐米不纯53 在 正丁基锂 、 硫酸 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 异丙醚 为溶剂， 反应 2.0h， 生成 硼替佐米杂质61
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF BORTEZOMIB
  [FR] PROCÉDÉ DE PRÉPARATION DE BORTÉZOMIB

  摘要：

  公开号：

  WO2011098963A9

文献信息

• [EN] NEUROTENSIN RECEPTOR BINDING CONJUGATES AND FORMULATIONS THEREOF<br/>[FR] CONJUGUÉS DE LIAISON AU RÉCEPTEUR DE LA NEUROTENSINE ET FORMULATIONS ASSOCIÉES
  申请人：TARVEDA THERAPEUTICS INC

  公开号：WO2017180834A1

  公开（公告）日：2017-10-19

  Conjugates of an active agent attached to a neurotensin receptor-binding targeting moiety via a linker have been designed. Nanoparticles and microparticles comprising such conjugates can provide improved temporospatial delivery of the active agent and/or improved biodistribution. Methods of making the conjugates, the particles, and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer or other diseases.

  已设计出将活性剂与神经肽受体结合靶向基团通过连接剂连接的共轭物。包含这种共轭物的纳米颗粒和微粒可以提供改善活性剂的时间空间传递和/或改善生物分布的效果。提供了制备这些共轭物、颗粒和其配方的方法。提供了将这些配方用于治疗或预防癌症或其他疾病的方法，例如向需要的受试者施用这些配方的方法。
• Boronic ester and acid compounds
  申请人：ProScript, Inc.

  公开号：US05780454A1

  公开（公告）日：1998-07-14

  Disclosed herein is a method for reducing the rate of degradation of proteins in an animal comprising contacting cells of the animal with certain boronic ester and acid compounds. Also disclosed herein are novel boronic ester and acid compounds, their synthesis and uses.

  本文公开了一种减少动物蛋白质降解速率的方法，包括使用某些硼酸酯和酸化合物接触动物的细胞。本文还公开了新型硼酸酯和酸化合物，它们的合成和用途。
• [EN] SYNTHESIS OF BORONIC ESTER AND ACID COMPOUNDS<br/>[FR] SYNTHESE D'ESTER BORIQUE ET DE COMPOSES ACIDES
  申请人：MILLENNIUM PHARM INC

  公开号：WO2005097809A2

  公开（公告）日：2005-10-20

  The invention relates to the synthesis of boronic ester and acid compounds. More particularly, the invention provides improved synthetic processes for the large-scale production of boronic ester and acid compounds, including the peptide boronic acid proteasome inhibitor bortezomib.

  本发明涉及硼酸酯和酸化合物的合成。更具体地说，本发明提供了改进的合成工艺，用于大规模生产硼酸酯和酸化合物，包括肽硼酸蛋白酶体抑制剂博瑞唑胺。
• Synthesis of boronic ester and acid compounds
  申请人：Pickersgill Fraser I.

  公开号：US20050240047A1

  公开（公告）日：2005-10-27

  The invention relates to the synthesis of boronic ester and acid compounds. More particularly, the invention provides improved synthetic processes for the large-scale production of boronic ester and acid compounds, including the peptide boronic acid proteasome inhibitor bortezomib.

  本发明涉及硼酸酯和酸化合物的合成。更具体地说，本发明提供了用于大规模生产硼酸酯和酸化合物的改进合成过程，包括肽硼酸蛋白酶体抑制剂博特泽米布。
• PROCESS FOR THE PREPARATION OF BORTEZOMIB
  申请人：Kumar Satish

  公开号：US20130085277A1

  公开（公告）日：2013-04-04

  The present invention relates to a process for the preparation of bortezomib (Formula I) and its intermediates.

  本发明涉及一种制备硼替佐米（式I）及其中间体的方法。