1-tert-butyl 4-ethyl 4-(4-fluorophenylsulfonyl)piperidine-1,4-dicarboxylate | 226396-63-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-tert-butyl 4-ethyl 4-(4-fluorophenylsulfonyl)piperidine-1,4-dicarboxylate
• 英文别名: 1-O-tert-butyl 4-O-ethyl 4-(4-fluorophenyl)sulfonylpiperidine-1,4-dicarboxylate
• CAS: 226396-63-0
• 化学式: C₁₉H₂₆FNO₆S
• 分子量: 415.483
• InChiKey: XMASBEDUOXHTBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  98.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-tert-butyl 4-ethyl 4-(4-fluorophenylsulfonyl)piperidine-1,4-dicarboxylate 在 盐酸 、 potassium carbonate 作用下， 以 醋酸异丙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.17h， 生成 ethyl 4-(4-fluorophenylsulfonyl)-1-(prop-2-ynyl)piperidine-4-carbox-ylate
  参考文献：
  名称：

  含碳硼烷的基质金属蛋白酶 (MMP) 配体作为硼中子俘获疗法 (BNCT) 的候选者。

  摘要：

  基于先前报道的强效选择性砜异羟肟酸酯抑制剂 SC-76276、SC-78080 (SD-2590) 和 SC-77964，已经设计并合成了有效的 MMP 抑制剂，通过点击化学添加富硼碳硼烷簇靶向已知上调明胶酶的肿瘤细胞。与 MMP-2 对接表明结合涉及异羟肟酸锌结合基团、砜部分与肽骨架残基 Leu82 和 Leu83 的关键 H 键，以及与深 P1' 口袋的疏水相互作用。两种三唑区域异构体中更有效的一种的 IC 50与 MMP-2 相比为 3.7 nM，IC 50与 MMP-9 相比为 46 nM。

  DOI：

  10.1002/cmdc.202000470
• 作为产物：
  描述：

  N-Boc-4-哌啶甲酸乙酯 在 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 41.5h， 生成 1-tert-butyl 4-ethyl 4-(4-fluorophenylsulfonyl)piperidine-1,4-dicarboxylate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of β- and α-Piperidine Sulfone Hydroxamic Acid Matrix Metalloproteinase Inhibitors with Oral Antitumor Efficacy

  摘要：

  alpha-Piperidine-beta-sulfone hydroxamate derivatives were explored that are potent for matrix metalloproteinases (MMP)-2, -9, and -13 and are sparing of MMP-1. The investigation of the beta-sulfones subsequently led to the discovery of hitherto unknown alpha-sulfone hydroxamates that are superior to the corresponding beta-sulfones in potency for target MMPs, selectivity vs MMP-1, and exposure when dosed orally. alpha-Tiperidine-alpha-sulfone, hydroxamate 35f (SC-276) was advanced through antitumor and antiangiogenesis assays and was selected for development. Compound 35f demonstrates excellent antitumor activity vs MX-1 breast tumor in mice when dosed orally as monotherapy or in combination with paclitaxel.

  DOI：

  10.1021/jm0500875

文献信息

• Aromatic sulfone hydroxamates and their use as protease inhibitors
  申请人：——

  公开号：US20040010019A1

  公开（公告）日：2004-01-15

  This invention is directed to aromatic sulfone hydroxamates (also known as “aromatic sulfone hydroxamic acids”) and salts thereof that, inter alia, inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. This invention also is directed to a prevention or treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.

  这项发明涉及芳香砜羟肟酸酯（也称为“芳香砜羟肟酸”）及其盐，该化合物在抑制基质金属蛋白酶（也称为“基质金属蛋白酶”或“MMP”）活性和/或聚集素酶活性方面具有作用。该发明还涉及一种预防或治疗方法，包括向动物，特别是患有（或易患）与MMP和/或聚集素酶活性相关的病理状况的哺乳动物，施用此类化合物或盐以达到抑制MMP和/或聚集素酶的有效量。
• [EN] CARBORANE HYDROXAMIC ACID MATRIX METALLOPROTEINASE INHIBITORS AND AGENTS FOR BORON NEUTRON CAPTURE THERAPY<br/>[FR] INHIBITEURS DE MÉTALLOPROTÉINASE MATRICIELLE D'ACIDE HYDROXAMIQUE CARBORANE ET AGENTS POUR UNE THÉRAPIE PAR CAPTURE DE NEUTRONS PAR LE BORE
  申请人：UNIV LOYOLA CHICAGO

  公开号：WO2020006384A1

  公开（公告）日：2020-01-02

  Disclosed herein are novel carborane hydroxamic acid matrix metalloproteinase ("MMP") inhibitors and agents bearing borane-containing moieties and methods for their use in treating or preventing a disease, such as cancer and rheumatoid arthritis. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salt thereof: Formula (I) wherein the substituents are as described.

  本文披露了新型碳硼烷羟肟酸基金属蛋白酶抑制剂和含硼基团的药物，以及它们在治疗或预防疾病（如癌症和类风湿性关节炎）中的使用方法。具体来说，本文披露了化合物的结构式（I）及其药用盐：结构式（I）中的取代基如所述。
• MMP-TARGETED THERAPEUTIC AND/OR DIAGNOSTIC NANOCARRIERS
  申请人：Mallinckrodt Inc.

  公开号：US20130183236A1

  公开（公告）日：2013-07-18

  The present invention provides targeted delivery compositions and methods of using the compositions for treating and diagnosing a disease state in a subject.

  本发明提供了针对性递送组合物以及使用这些组合物治疗和诊断受试者疾病状态的方法。
• [EN] OPTICAL AGENTS FOR IMAGING AND VISUALIZATION OF MATRIX METALLOPROTEINASE ENZYMES<br/>[FR] AGENTS OPTIQUES PERMETTANT D'OBTENIR DES IMAGES DE MÉTALLOPROTÉASES MATRICIELLES ET DE LES VISUALISER
  申请人：MALLINCKRODT LLC

  公开号：WO2013039851A1

  公开（公告）日：2013-03-21

  The invention relates generally to optical agents for biomedical applications including imaging, visualization, phototherapy and diagnostic monitoring of cells and tissue expressing MMPs and/or tissues associated with the expression of MMPs. In some embodiments, for example, optical agents of the present invention selectively bind to, or otherwise preferentially associate with, a target tissue expressing one or more MMPs, and function to couple electromagnetic radiation into and/or out of the target tissue, for example via optical absorption, fluorescence, scattering and/or optoacoustic processes.

  该发明通常涉及用于生物医学应用的光学试剂，包括成像、可视化、光疗和诊断监测表达MMPs和/或与MMPs表达相关的细胞和组织。在某些实施例中，例如，本发明的光学试剂选择性地结合到或以其他方式优先与表达一个或多个MMPs的靶组织结合，并且功能是将电磁辐射耦合到和/或从靶组织中传出，例如通过光吸收、荧光、散射和/或光声过程。
• An Efficient Oxidation of Sulfides to Sulfones with Urea–Hydrogen Peroxide in the Presence of Phthalic Anhydride in Ethyl Acetate
  作者：Igor Likhotvorik、Marlon Lutz、Marta Wenzler

  DOI：10.1055/s-0037-1609446

  日期：2018.6

  environmentally benign oxidation of substituted sulfides directly to their corresponding sulfones is described. Using urea-hydrogen peroxide and phthalic anhydride in ethyl acetate clean conversion into the sulfone was achieved without observation of the possible sulfoxide oxidation product. A metal-free, environmentally benign oxidation of substituted sulfides directly to their corresponding sulfones is described

  摘要 描述了无金属的，环境友好的取代的硫化物直接氧化为其相应的砜的方法。在乙酸乙酯中使用尿素-过氧化氢和邻苯二甲酸酐，可实现向砜的清洁转化，而无需观察到可能的亚砜氧化产物。 描述了无金属的，环境友好的取代的硫化物直接氧化为其相应的砜的方法。在乙酸乙酯中使用尿素-过氧化氢和邻苯二甲酸酐，可实现向砜的清洁转化，而无需观察到可能的亚砜氧化产物。