tert-butyl 2-{[(4-fluorophenyl)sulfonyl]amino}acetate | 213015-69-1

• 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: tert-butyl 2-{[(4-fluorophenyl)sulfonyl]amino}acetate
• 英文别名: N-[(4-flouro-phenyl)sulphonyl]glycine, 1,1-dimethylethyl ester；tert-butyl 2-[(4-fluorophenyl)sulfonylamino]acetate
• CAS: 213015-69-1
• 化学式: C₁₂H₁₆FNO₄S
• 分子量: 289.328
• InChiKey: SSTJRYXDQFRAMY-UHFFFAOYSA-N

物化性质

• 沸点：
  382.6±52.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-{[(4-fluorophenyl)sulfonyl]amino}acetate 在 caesium carbonate 、 三氟乙酸 、 三苯基二氯化膦 作用下， 以 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 20.25h， 生成
  参考文献：
  名称：

  Identification and Characterization of AES-135, a Hydroxamic Acid-Based HDAC Inhibitor That Prolongs Survival in an Orthotopic Mouse Model of Pancreatic Cancer

  摘要：

  Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, incurable cancer with a 20% 1 year survival rate. While standard-of-care therapy can prolong life in a small fraction of cases, PDAC is inherently resistant to current treatments, and novel therapies are urgently required. Histone deacetylase (HDAC) inhibitors are effective in killing pancreatic cancer cells in in vitro PDAC studies, and although there are a few clinical studies investigating combination therapy including HDAC inhibitors, no HDAC drug or combination therapy with an HDAC drug has been approved for the treatment of PDAC. We developed an inhibitor of HDACs, AES-135, that exhibits nanomolar inhibitory activity against HDAC3, HDAC6, and HDAC11 in biochemical assays. In a three-dimensional coculture model, AES-135 kills low-passage patient-derived tumor spheroids selectively over surrounding cancer-associated fibroblasts and has excellent pharmacokinetic properties in vivo. In an orthotopic murine model of pancreatic cancer, AES-135 prolongs survival significantly, therefore representing a candidate for further preclinical testing.

  DOI：

  10.1021/acs.jmedchem.8b01957
• 作为产物：
  描述：

  4-氟苯磺酰氯 生成 tert-butyl 2-{[(4-fluorophenyl)sulfonyl]amino}acetate
  参考文献：
  名称：

  Acetylenic TACE inhibitors. Part 1. SAR of the acyclic sulfonamide hydroxamates

  摘要：

  The SAR of a series of potent sulfonamide hydroxamate TACE inhibitors, all bearing a butynyloxy P1' group, was explored. In particular, compound 5j has excellent in vitro potency against isolated TACE enzyme and in cells, good selectivity over MMP-1 and MMP-9, and oral activity in an in vivo model of TNF-alpha production and a collagen-induced arthritis model. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00514-6

文献信息

• N-(4-sulfonylaryl)Cyclylamine 2-hydroxyethylamines as beta-3 adrenergic receptor agonists
  申请人：American Home Products Corporation

  公开号：US20020028797A1

  公开（公告）日：2002-03-07

  This invention provides compounds of Formula I having the structure 1 wherein R 1 , R 2 , R 3 , R 4 , W, X, and Y are as defined hereinbefore or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.

  这项发明提供了具有结构1的化合物，其中R1、R2、R3、R4、W、X和Y如前文所定义，或其药用盐，这些化合物可用于治疗与胰岛素抵抗或高血糖相关的代谢紊乱。
• N-(4-sulfonylaryl)cyclylamine-2-hydroxyethylamines as beta-3 adrenergic receptor agonists
  申请人：Wyeth

  公开号：US20030027795A1

  公开（公告）日：2003-02-06

  This invention provides compounds of Formula I having the structure 1 wherein R 1 , R 2 , R 3 , R 4 , W, X, and Y are as defined hereinbefore or a pharmaceutically acceptable salt thereof, which are useful in treating metabolic disorders related to insulin resistance or hyperglycemia.

  本发明提供了具有结构1的化合物，其中R1，R2，R3，R4，W，X和Y如前所定义，或其药学上可接受的盐，用于治疗与胰岛素抵抗或高血糖相关的代谢性疾病。
• Thioaryl sulfonamide hydroxamic acid compounds
  申请人：——

  公开号：US20040034071A1

  公开（公告）日：2004-02-19

  A thioaryl sulfonamide hydroxamic acid compound that, inter alia, inhibits matrix metalloprotease activity is disclosed, as are a treatment process that comprises administering a contemplated thioaryl sulfonamide hydroxamic acid compound in a MMP enzyme-inhibiting effective amount to a host having a condition associated with pathological matrix metalloprotease activity.

  本发明揭示了一种硫代芳基磺酰胺羟肟酸化合物，其中包括抑制基质金属蛋白酶活性，还揭示了一种治疗过程，其包括向具有与病理基质金属蛋白酶活性相关的病情的宿主施用考虑到的硫代芳基磺酰胺羟肟酸化合物，以MMP酶抑制有效量。
• 具有HDAC抑制活性的化合物、制备方法、组合物及其用途
  申请人：北京鑫开元医药科技有限公司

  公开号：CN114605348A

  公开（公告）日：2022-06-10

  本发明属于药物技术领域，尤其涉及具有HDAC抑制活性的化合物、制备方法、组合物及其用途，所述化合物是具有式I结构的化合物或其药学上可接受的盐：，式中，R1代表无取代的芳基、取代的芳基、无取代的杂芳基或取代的杂芳基，本发明提供的化合物具有HDAC抑制活性，通过抑制HDAC的活性，可以作为抗肿瘤药物用于治疗与HDAC活性异常相关的疾病，对研究肿瘤药物的开发有重要的意义。
• Class I/IIb-Selective HDAC Inhibitor Exhibits Oral Bioavailability and Therapeutic Efficacy in Acute Myeloid Leukemia
  作者：Andrew E. Shouksmith、Justyna M. Gawel、Nabanita Nawar、Diana Sina、Yasir S. Raouf、Shazreh Bukhari、Liying He、Alexandra E. Johns、Pimyupa Manaswiyoungkul、Olasunkanmi O. Olaoye、Aaron D. Cabral、Abootaleb Sedighi、Elvin D. de Araujo、Patrick T. Gunning

  DOI：10.1021/acsmedchemlett.9b00471

  日期：2020.1.9

  The HDAC inhibitor 4-tert-butyl-N-(4-(hydroxycarbamoyl)phenyl)benzamide (AES-350, 51) was identified as a promising preclinical candidate for the treatment of acute myeloid leukemia (AML), an aggressive malignancy with a meagre 24% 5-year survival rate. Through screening of low-molecular-weight analogues derived from the previously discovered novel HDAC inhibitor, AES-135, compound 51 demonstrated greater HDAC isoform selectivity, higher cytotoxicity in MV4-11 cells, an improved therapeutic window, and more efficient absorption through cellular and lipid membranes. Compound 51 also demonstrated improved oral bioavailability compared to SAHA in mouse models. A broad spectrum of experiments, including FACS, ELISA, and Western blotting, were performed to support our hypothesis that 51 dose-dependently triggers apoptosis in AML cells through HDAC inhibition.