(S)-tert-butyl ((8-nitrodibenzo[b,d]furan-3-yl)sulfonyl)-L-valinate | 1025718-85-7

• 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 ((8-nitrodibenzo[b,d]furan-3-yl)sulfonyl)-L-valinate
• 英文别名: (S)-tert-butyl 3-methyl-2-(8-nitrodibenzo[b,d]furan-3-sulfonamido)butanoate；(S)-3-methyl-2-(8-nitro-dibenzofuran-3-sulfonylamino)-butyric acid tert-butyl ester；tert-butyl (2S)-3-methyl-2-[(8-nitrodibenzofuran-3-yl)sulfonylamino]butanoate
• CAS: 1025718-85-7
• 化学式: C₂₁H₂₄N₂O₇S
• 分子量: 448.497
• InChiKey: OOQXRAOMCORVJI-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  31
• 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：
  140
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl ((8-nitrodibenzo[b,d]furan-3-yl)sulfonyl)-L-valinate 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 88.0h， 生成 (S)-tert-butyl ((8-(4-iodobenzamido)dibenzo[b,d]furan-3-yl)sulfonyl)-L-valinate
  参考文献：
  名称：

  Synthesis of radioiodinated probes targeted toward matrix metalloproteinase-12

  摘要：

  Matrix metalloproteinase-12 (MMP-12, macrophage elastase) is a member of the MMP family that is responsible for the degradation of extracellular matrix, and is associated with the inflammatory process of chronic obstructive pulmonary disease (COPD). COPD, characterized by progressive and irreversible airflow obstruction, is recently a major cause of mortality and morbidity worldwide. Herein, to develop radioiodinated probes for the early diagnosis of COPD, we designed and synthesized novel MMP-12-targeted dibenzofuran compounds (1-3) with a variety of linker structures (carbamate, amide, and sulfonamide). In competitive enzyme activity assays, it was revealed that the linker structures significantly affected the inhibitory activity against and selectivity for MMP-12. Compound 1, with carbamate linker, demonstrated potent MMP-12 inhibitory activity (IC50 = 8.5 nM) compared to compound 2, with amide linker, and compound 3, with sulfonamide linker. Using bromo-substituted carbamate 13 as a radioiodination precursor, [I-125] 1 was successfully prepared to high radiochemical purity (over 98%) and good specific radioactivity (4.1 GBq/mu mol). These results suggest that radioiodinated compound 1 is potent as a novel MMP-12-targeted probe. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.11.027
• 作为产物：
  描述：

  二苯并呋喃-3-磺酰氯 在 硝酸 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 (S)-tert-butyl ((8-nitrodibenzo[b,d]furan-3-yl)sulfonyl)-L-valinate
  参考文献：
  名称：

  Synthesis of radioiodinated probes targeted toward matrix metalloproteinase-12

  摘要：

  Matrix metalloproteinase-12 (MMP-12, macrophage elastase) is a member of the MMP family that is responsible for the degradation of extracellular matrix, and is associated with the inflammatory process of chronic obstructive pulmonary disease (COPD). COPD, characterized by progressive and irreversible airflow obstruction, is recently a major cause of mortality and morbidity worldwide. Herein, to develop radioiodinated probes for the early diagnosis of COPD, we designed and synthesized novel MMP-12-targeted dibenzofuran compounds (1-3) with a variety of linker structures (carbamate, amide, and sulfonamide). In competitive enzyme activity assays, it was revealed that the linker structures significantly affected the inhibitory activity against and selectivity for MMP-12. Compound 1, with carbamate linker, demonstrated potent MMP-12 inhibitory activity (IC50 = 8.5 nM) compared to compound 2, with amide linker, and compound 3, with sulfonamide linker. Using bromo-substituted carbamate 13 as a radioiodination precursor, [I-125] 1 was successfully prepared to high radiochemical purity (over 98%) and good specific radioactivity (4.1 GBq/mu mol). These results suggest that radioiodinated compound 1 is potent as a novel MMP-12-targeted probe. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.11.027

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：——
• A Selective Matrix Metalloprotease 12 Inhibitor for Potential Treatment of Chronic Obstructive Pulmonary Disease (COPD): Discovery of (<i>S</i>)-2-(8-(Methoxycarbonylamino)dibenzo[<i>b</i>,<i>d</i>]furan-3-sulfonamido)-3-methylbutanoic acid (MMP408)
  作者：Wei Li、Jianchang Li、Yuchuan Wu、Junjun Wu、Rajeev Hotchandani、Kristina Cunningham、Iain McFadyen、Joel Bard、Paul Morgan、Franklin Schlerman、Xin Xu、Steve Tam、Samuel J. Goldman、Cara Williams、Joseph Sypek、Tarek S. Mansour

  DOI：10.1021/jm900093d

  日期：2009.4.9

  Matrix metalloprotease 12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have-been found in the lung of human COPD patients. MMP408 (14), a potent and selective MMP-12 inhibitor, was derived from a potent matrix metalloprotease 2 and 13 inhibitor via lead optimization and has good physical properties and bioavailability. The compound blocks rhMMP-12-induced lung inflammation in a mouse model and was advanced for further development for the treatment of COPD.
• Identification of an Orally Efficacious Matrix Metalloprotease 12 Inhibitor for Potential Treatment of Asthma
  作者：Wei Li、Jianchang Li、Yuchuan Wu、Fabio Rancati、Stefania Vallese、Luca Raveglia、Junjun Wu、Rajeev Hotchandani、Nathan Fuller、Kristina Cunningham、Paul Morgan、Susan Fish、Rustem Krykbaev、Xin Xu、Steve Tam、Samuel J. Goldman、William Abraham、Cara Williams、Joseph Sypek、Tarek S. Mansour

  DOI：10.1021/jm900809r

  日期：2009.9.10

  MMP-12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have been observed in the lungs of asthmatic patients. Compound 27 was identified as a potent and selective MMP-12 inhibitor possessing good physicochemical properties. In pharmacological studies, the compound was orally efficacious in an MMP-12 induced ear-swelling inflammation model in the mouse with a good dose response. This compound also exhibited oral efficacy in a naturally Ascaris-sensitized sheep asthma model showing significant inhibition of the late phase response to allergen challenge. This compound has been considered for further development as a treatment therapy for asthma.
• [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.