tert-butyl ((4-methoxyphenyl)sulfonyl)glycinate

• 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 ((4-methoxyphenyl)sulfonyl)glycinate
• 英文别名: (4-methoxybenzenesulfonylamino) acetic acid t-butyl ester；tert-butyl 2-[(4-methoxyphenyl)sulfonylamino]acetate
• 化学式: C₁₃H₁₉NO₅S
• 分子量: 301.364
• InChiKey: FQVXNHAREUSTHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl ((4-methoxyphenyl)sulfonyl)glycinate 在 草酰氯 、 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 三氟乙酸 、 三苯基二氯化膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 54.25h， 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：

  甘氨酸叔丁酯 、 对甲氧基苯磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 tert-butyl ((4-methoxyphenyl)sulfonyl)glycinate
  参考文献：
  名称：

  Arylsulfonyl hydroxamic acid derivatives as MMP and TNF inhibitors

  摘要：

  一种化合物的化学式为##STR1##其中R.sup.1、R.sup.2、R.sup.3、R.sup.4、R.sup.5、R.sup.6、R.sup.7、R.sup.8、R.sup.9和Ar如上所定义，在治疗关节炎、癌症、组织溃疡、再狭窄、牙周病、表皮溃疡性水疱病、巩膜炎和其他以基质金属蛋白酶活性为特征的疾病，以及艾滋病、败血症、脓毒症休克和其他涉及TNF产生的疾病中有用。

  公开号：

  US05861510A1

文献信息

• Arylsulfonyl Hydroxamic Acid derivatives as MMP and TNF inhibitors
  申请人：Pfizer Inc.

  公开号：US06509337B1

  公开（公告）日：2003-01-21

  A compound of the formula wherein R1-R9 and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, tissue ulceration, restenosis, periodontal disease, epidemrolysis bullosa, scleritis and other disease characterized by matrix metalloproteinase activity, as well as AIDS, sepsis, septic shock and other diseases involving the production of TNF.

  一种化合物的公式，其中R1-R9和Ar的定义如上所述，可用于治疗从关节炎，癌症，组织溃疡，再狭窄，牙周病，表皮松解症，巩膜炎和其他以基质金属蛋白酶活性为特征的疾病，以及艾滋病，败血症，脓毒症休克和其他涉及TNF生成的疾病。
• Replacement of a Naphthalene Scaffold in Kelch-like ECH-Associated Protein 1 (KEAP1)/Nuclear Factor (Erythroid-derived 2)-like 2 (NRF2) Inhibitors
  作者：Benjamin G. Richardson、Atul D. Jain、Haranatha R. Potteti、Phillip R. Lazzara、Brian P. David、Chandra R. Tamatam、Ewelina Choma、Kornelia Skowron、Katherine Dye、Zamia Siddiqui、Yue-Ting Wang、Aleksej Krunic、Sekhar P. Reddy、Terry W. Moore

  DOI：10.1021/acs.jmedchem.8b01133

  日期：2018.9.13

  Activators of nuclear factor-erythroid 2-related factor 2 (NRF2) could lead to promising therapeutics for prevention and treatment of oxidative stress and inflammatory disorders. Ubiquitination and subsequent degradation of the transcription factor NRF2 is mediated by Kelch-like ECH-associated protein-1 (KEAP1). Inhibition of the KEAP1/NRF2 interaction with small molecules leads to NRF2 activation. Previously, we and others described naphthalene-based NRF2 activators, but the 1,4-diaminonaphthalene scaffold may not represent a drug-like scaffold. Paying particular attention to aqueous solubility, metabolic stability, potency, and mutagenicity, we modified a previously known, naphthalene-based nonelectrophilic NRF2 activator to give a series of non-naphthalene and heterocyclic scaffolds. We found that, compared to previously reported naphthalene-based compounds, a 1,4-isoquinoline scaffold provides a better mutagenic profile without sacrificing potency, stability, or solubility.
• ARYLSULFONYL HYDROXAMIC ACID DERIVATIVES AS MMP AND TNF INHIBITORS
  申请人：PFIZER INC.

  公开号：EP0821671A1

  公开（公告）日：1998-02-04
• US5861510A
  申请人：——

  公开号：US5861510A

  公开（公告）日：1999-01-19
• US6509337B1
  申请人：——

  公开号：US6509337B1

  公开（公告）日：2003-01-21