Methyl 2-[(4-fluorophenyl)sulfonylamino]acetate | 346696-78-4

• 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: Methyl 2-[(4-fluorophenyl)sulfonylamino]acetate
• CAS: 346696-78-4
• 化学式: C₉H₁₀FNO₄S
• mdl: MFCD01213861
• 分子量: 247.247
• InChiKey: NEKOMTDETIOPCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.222
• 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：

  Methyl 2-[(4-fluorophenyl)sulfonylamino]acetate 在 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以100%的产率得到2-(4-fluorophenylsulfonamido)acetic acid
  参考文献：
  名称：

  Class I/IIb-Selective HDAC Inhibitor Exhibits Oral Bioavailability and Therapeutic Efficacy in Acute Myeloid Leukemia

  摘要：

  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.

  DOI：

  10.1021/acsmedchemlett.9b00471
• 作为产物：
  描述：

  4-氟苯磺酰氯 、 甘氨酸甲酯盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以75%的产率得到Methyl 2-[(4-fluorophenyl)sulfonylamino]acetate
  参考文献：
  名称：

  Class I/IIb-Selective HDAC Inhibitor Exhibits Oral Bioavailability and Therapeutic Efficacy in Acute Myeloid Leukemia

  摘要：

  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.

  DOI：

  10.1021/acsmedchemlett.9b00471

文献信息

• First insight into structure-activity relationships of selective meprin β inhibitors
  作者：Daniel Ramsbeck、Antje Hamann、Dagmar Schlenzig、Stephan Schilling、Mirko Buchholz

  DOI：10.1016/j.bmcl.2017.04.012

  日期：2017.6

  The astacin proteases meprin α and β are emerging drug targets for treatment of disorders such as kidney failure, fibrosis or inflammatory bowel disease. However, there are only few inhibitors of both proteases reported to date. Starting from NNGH as lead structure, a detailed elaboration of the structure-activity relationship of meprin β inhibitors was performed, leading to compounds with activities

  Astacin蛋白酶meprinα和β是用于治疗诸如肾衰竭，纤维化或炎性肠病等疾病的新兴药物靶标。但是，迄今报道的两种蛋白酶的抑制剂很少。从NNGH作为先导结构开始，对meprinβ抑制剂的构效关系进行了详细的阐述，从而得到了具有较低纳摩尔范围活性的化合物。考虑到meprinβ对P1'位置的酸性残基的偏爱，对化合物进行了优化。与其他结构相关的金属蛋白酶（如MMP-2或ADAM10）相比，酸性修饰诱导出有效的抑制作用和> 100倍的选择性。
• Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs)
  作者：Emanuele Attolino、Vito Calderone、Elisa Dragoni、Marco Fragai、Barbara Richichi、Claudio Luchinat、Cristina Nativi

  DOI：10.1016/j.ejmech.2010.09.057

  日期：2010.12

  N-Arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water. (C) 2010 Elsevier Masson SAS. All rights reserved.