(S)-tert-butyl 2-(8-bromodibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoate | 1025719-45-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (S)-tert-butyl 2-(8-bromodibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoate
• 英文别名: tert-butyl (2S)-2-[(8-bromodibenzofuran-3-yl)sulfonylamino]-3-methylbutanoate
• CAS: 1025719-45-2
• 化学式: C₂₁H₂₄BrNO₅S
• 分子量: 482.395
• InChiKey: CRMPMGKAHQLSKP-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  94
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 2-(8-bromodibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoate 在 copper(l) iodide 、 sodium azide 、 sodium ascorbate 、 N,N'-二甲基乙二胺 作用下， 以 乙醇 、 水 为溶剂， 反应 0.5h， 以94%的产率得到tert-butyl [(8-azidodibenzo[b,d]furan-3-yl)sulfonyl]-(S)-valinate
  参考文献：
  名称：

  设计，（放射）合成以及体外和体内评估高选择性和有效基质金属蛋白酶12（MMP-12）抑制剂作为正电子发射断层显像的放射性示踪剂

  摘要：

  活化基质金属蛋白酶（MMPs）的水平失调与不同的病状相关，例如癌症，动脉粥样硬化，神经炎症和关节炎。因此，用正电子发射断层扫描（PET）对MMP进行成像是诊断MMP相关疾病的有力工具。此外，为了区分单个MMP在特定病理生理过程中的独特功能和作用，必须使用放射性标记的示踪剂（例如氟18标记的MMP抑制剂（MMPI））来实现其特定的成像。因此，制备了氟化的基于二苯并呋喃磺酰胺的MMPI，其显示出对MMP-12的优异抑制作用以及对MMP-12的选择性，其优于其他MMP。MMP-12是慢性阻塞性肺疾病（COPD）和动脉粥样硬化等疾病中的关键酶。4，9和19）从该库中选择，和放射氟化类似物（[ 18 F] 4，[ 18 F] 9，和[ 18 F] 19）成功地合成。初步的体外血清稳定性和放射性标记的MMPIs与PET的体内生物分布研究表明，它们对于优选的MMP-12成像具有潜在的好处。

  DOI：

  10.1021/acs.jmedchem.8b00200
• 作为产物：
  描述：

  3-氨基二苯并呋喃 在 盐酸 、 二氧化硫 、 溴 、 氯 、 溶剂黄146 、 N,N-二异丙基乙胺 、 copper dichloride 、 sodium nitrite 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 反应 52.0h， 生成 (S)-tert-butyl 2-(8-bromodibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoate
  参考文献：
  名称：

  Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD)

  摘要：

  Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodeling of damaged alveoli in COPD and asthma. The goal of this project is to develop and identify an orally potent and selective small molecule inhibitor of MMP-12 for treatment of COPD and asthma. Syntheses and structure-activity relationship (SAR) studies of a series of dibenzofuran (DBF) sulfonamides as MMP-12 inhibitors are described. Potent inhibitors of MMP-12 with excellent selectivity against other MMPs were identified. Compound 26 (MMP118), which exhibits excellent oral efficacy in the MMP-12 induced ear-swelling inflammation and lung inflammation mouse models, had been successfully advanced into Development Track status. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.11.046

文献信息

• TRICYCLIC COMPOUNDS AS MATRIX METALLOPROTEINASE INHIBITORS
  申请人：LI Wei

  公开号：US20100227859A1

  公开（公告）日：2010-09-09

  The present teachings relate to compounds of formula I: and pharmaceutically acceptable salts and esters thereof, wherein R1, R2, R3, R4, X, and Y are as defined herein. The present teachings also provide methods of making the compounds of formula I and methods of inhibiting matrix metalloproteinases, in particular, MMP-12, that may be involved in pathological disorders found in mammals, including a human.

  目前的教导与式I的化合物有关：及其药用盐和酯，其中R1、R2、R3、R4、X和Y如本文所定义。目前的教导还提供了制备式I化合物的方法以及抑制基质金属蛋白酶的方法，特别是可能参与哺乳动物中发现的病理性疾病，包括人类。
• WO2008/57254
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] TRICYCLIC COMPOUNDS AS MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] COMPOSÉS TRICYCLIQUES SERVANT D'INHIBITEURS DES MÉTALLOPROTÉASES MATRICIELLES
  申请人：WYETH CORP

  公开号：WO2008057254A2

  公开（公告）日：2008-05-15

  [EN] The present invention relates to compositions of the formula (I): and pharmaceutically acceptable salts, hydrates, or esters thereof, wherein R¹, R², R³, R⁴, R⁵, X, and Y are as defined herein. The present teachings also provide methods of making the compounds of formula I, and methods of treating pathologic conditions or disorders mediated wholly or in part by matrix metalloproteinases, such as asthma and chronic obstructive pulmonary disease, comprising administering a therapeutically effective amount of a compound of formula (I) to a mammal (e.g., a human) in need thereof.
  [FR] La présente invention concerne des composés de formule (I) : et des sels, hydrates ou esters acceptables du point de vue pharmaceutique de ceux-ci, R¹, R², R³, R⁴, R⁵, X et Y étant tels que définis ici. La présente invention concerne également des procédés de fabrication des composés de formule (I) et des procédés de traitement d'affections ou troubles pathologiques induits entièrement ou en partie par des métalloprotéases matricielles, tels que l'asthme et une bronchopneumopathie chronique obstructive, lesquels consistent à administrer une quantité efficace du point de vue thérapeutique d'un composé de formule (I) à un mammifère (par exemple à un humain) qui en a besoin.
• [EN] TRICYCLIC COMPOUNDS AS MATRIX METALLOPROTEINASE INHIBITORS<br/>[FR] COMPOSÉS TRICYCLIQUES EN TANT QU'INHIBITEURS DE MÉTALLOPROTÉINASE MATRICIELLE
  申请人：WYETH CORP

  公开号：WO2008137816A2

  公开（公告）日：2008-11-13

  (EN) The present teachings relate to compounds of formula I: and pharmaceutically acceptable salts and esters thereof, wherein R1, R2, R3, R4, X, and Y are as defined herein. The present teachings also provide methods of making the compounds of formula I and methods of inhibiting matrix metalloproteinases, in particular, MMP-12, that may be involved in pathological disorders found in mammals, including a human.(FR) L'invention concerne des composés de formule I et des sels pharmaceutiquement acceptables et des ester de ceux-ci, R1, R2, R3, R4, X, et Y étant définis. Les présentes informations concernent également des procédés de préparation de composés de formule I et des procédés d'inhibition de métalloprotéinases matricielles, en particulier, MMP-12, qui peuvent être impliquées dans des troubles pathologiques rencontrés chez des mammifères, y compris chez l'homme.
• Discovery of potent and selective matrix metalloprotease 12 inhibitors for the potential treatment of chronic obstructive pulmonary disease (COPD)
  作者：Yuchuan Wu、Jianchang Li、Junjun Wu、Paul Morgan、Xin Xu、Fabio Rancati、Stefania Vallese、Luca Raveglia、Rajeev Hotchandani、Nathan Fuller、Joel Bard、Kristina Cunningham、Susan Fish、Rustem Krykbaev、Steve Tam、Samuel J. Goldman、Cara Williams、Tarek S. Mansour、Eddine Saiah、Joseph Sypek、Wei Li

  DOI：10.1016/j.bmcl.2011.11.046

  日期：2012.1

  Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with irreversible progressive airflow limitation. Matrix metalloproteinase-12 (MMP-12) has been characterized to be one of the major proteolytic enzymes to induce airway remodeling, destruction of elastin and the aberrant remodeling of damaged alveoli in COPD and asthma. The goal of this project is to develop and identify an orally potent and selective small molecule inhibitor of MMP-12 for treatment of COPD and asthma. Syntheses and structure-activity relationship (SAR) studies of a series of dibenzofuran (DBF) sulfonamides as MMP-12 inhibitors are described. Potent inhibitors of MMP-12 with excellent selectivity against other MMPs were identified. Compound 26 (MMP118), which exhibits excellent oral efficacy in the MMP-12 induced ear-swelling inflammation and lung inflammation mouse models, had been successfully advanced into Development Track status. (C) 2011 Elsevier Ltd. All rights reserved.