(S)-p-bromobenzenesulfinamide | 873586-57-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (S)-p-bromobenzenesulfinamide
• 英文别名: (S)-4-bromobenzenesulfinamide
• CAS: 873586-57-3
• 化学式: C₆H₆BrNOS
• 分子量: 220.09
• InChiKey: YRDOHKFPTGKJSJ-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-p-bromobenzenesulfinamide 在 titanium(IV) tetraethanolate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.5h， 生成 dibenzyl (SS,R)-N-(p-bromobenzenesulfinyl)-2-amino-2-methylpropylphosphonate
  参考文献：
  名称：

  α-Biphenylsulfonylamino 2-methylpropyl phosphonates: Enantioselective synthesis and selective inhibition of MMPs

  摘要：

  (R)-alpha-Biphenyisulfonylamino 2-methylpropyl phosphonates attain nM potency against several MMPs and are the most effective inhibitors based on phosphonate as zinc binding group. Since their preparation by direct N-acylation of expensive, enantiopure, alpha-aminophosphonic acids proceeds in low yields, we devised and evaluated a stereoselective and straightforward method of synthesis that avoids the unfavourable step of N-acylation. The key intermediate (R)-4-bromophenylsulfonylamino 2-methylpropyl phosphonate 9 was obtained by highly stereoselective addition of dibenzylphosphite to the enantiopure (S)-N-isobutylidene-p-bromobenzenesulfinamide 3, followed by oxidation with m-CPBA. Suzuki coupling of 9 with the desired arylboronic acids, gave the expected biphenylsulfonylamino derivatives in satisfactory yields. Liberation of the phosphonic group by hydrogenolysis led to the desired (R)-alpha-biphenylsulfonylamino 2-methylpropyl phosphonates 14a-i. Screening of the new compounds on MMP-1, -2, -3, -7, -8, -9, -13 and -14 showed IC50 in the range of nM in most cases. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.047
• 作为产物：
  描述：

  (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (S)-4-bromobenzenesulfinate 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以68%的产率得到(S)-p-bromobenzenesulfinamide
  参考文献：
  名称：

  Structural Insight into the Stereoselective Inhibition of MMP-8 by Enantiomeric Sulfonamide Phosphonates

  摘要：

  Potent and selective inhibitors of matrix metalloproteinases (MMPs), a family of zinc proteases that can degrade all the components of the extracellular matrix, could be useful for treatment of diseases such as cancer and arthritis. The most potent MMP inhibitors are based on hydroxamate as zinc-binding group (ZBG). alpha-Arylsulfonylamino phosphonates incorporate a particularly favorable combination of phosphonate as ZBG and arylsulfonylamino backbone so that their affinity exceptionally attains the nanomolar strength frequently observed for hydroxamate analogues. The detailed mode of binding of [1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate has been clarified by the crystal structures of the complexes that the R- and S-enantiomers respectively form with MMP-8. The reasons for the preferential MMP-8 inhibition by the R-phosphonate are underlined and the differences in the mode of binding of analogous alpha-arylsulfonylamino hydroxamates and carboxylates are discussed.

  DOI：

  10.1021/jm050787+

文献信息

• Fluorinated matrix metalloproteinases inhibitors—Phosphonate based potential probes for positron emission tomography
  作者：Bernd Beutel、Constantin G. Daniliuc、Burkhard Riemann、Michael Schäfers、Günter Haufe

  DOI：10.1016/j.bmc.2016.01.017

  日期：2016.2

  Fluorine-containing inhibitors of matrix metalloproteinases (MMPs) can serve as lead structures for the development of 18F-labeled radioligands. These compounds might be useful as non-invasive imaging probes to characterize pathologies associated with increased MMP activity. Results with a series of fluorinated analogs of a known biphenyl sulfonamide inhibitor have shown that fluorine can be incorporated

  基质金属蛋白酶（MMP）的含氟抑制剂可作为开发18 F标记放射性配体的先导结构。这些化合物可用作非侵入性成像探针，以表征与MMP活性增加相关的病理。一系列已知联苯磺酰胺抑制剂的氟化类似物的结果表明，氟可以掺入分子支架的两个不同位置，而不会显着降低纳摩尔范围内的效力。另外，已经证明了迄今未知的氟化叔磺酰胺作为MMP抑制剂的潜力。
• Enantioselective sulfinylation of alcohols and amines by condensation with sulfinates
  作者：Minghong Liao、Yonggui Liu、Hongyan Long、Qin Xiong、Xiaokang Lv、Zhongfu Luo、Xingxing Wu、Yonggui Robin Chi

  DOI：10.1016/j.chempr.2024.02.016

  日期：2024.3

  Achieving the preparation of enantiomerically enriched -stereogenic compounds is a long-standing objective in stereoselective synthesis, owing to the fundamental importance and broad applications of these chiral scaffolds in various fields. Despite recent significant advancements, catalyst-controlled stereoselective synthesis of -stereogenic compounds remains to be a considerable challenge, particularly

  由于这些手性支架在各个领域的根本重要性和广泛应用，实现对映体富集的立体化合物的制备是立体选择性合成的长期目标。尽管最近取得了重大进展，但催化剂控制的立体选择性合成β-立体化合物仍然是一个相当大的挑战，特别是通过小分子催化剂。在此，我们公开了一种通过形成混合亚磺酸酐来活化亚磺酸盐来对醇和胺进行高度实用和对映选择性亚磺酰化的有机催化策略。一种简单的天然奎宁催化剂通过空间拥挤部分调节反应物种的结构，有效控制亲核 S-O 和 S-N 键结构的化学和对映选择性，提供各种具有优异光学性质的手性亚磺酰基衍生物纯度。值得注意的是，该协议很容易促进与各种天然产物和商业药物的偶联，这可以为重要的生物学有趣分子的后期多样化提供有吸引力的策略。
• α-Biphenylsulfonylamino 2-methylpropyl phosphonates: Enantioselective synthesis and selective inhibition of MMPs
  作者：Alessandro Biasone、Paolo Tortorella、Cristina Campestre、Mariangela Agamennone、Serena Preziuso、Marika Chiappini、Elisa Nuti、Paolo Carelli、Armando Rossello、Fernando Mazza、Carlo Gallina

  DOI：10.1016/j.bmc.2006.10.047

  日期：2007.1

  (R)-alpha-Biphenyisulfonylamino 2-methylpropyl phosphonates attain nM potency against several MMPs and are the most effective inhibitors based on phosphonate as zinc binding group. Since their preparation by direct N-acylation of expensive, enantiopure, alpha-aminophosphonic acids proceeds in low yields, we devised and evaluated a stereoselective and straightforward method of synthesis that avoids the unfavourable step of N-acylation. The key intermediate (R)-4-bromophenylsulfonylamino 2-methylpropyl phosphonate 9 was obtained by highly stereoselective addition of dibenzylphosphite to the enantiopure (S)-N-isobutylidene-p-bromobenzenesulfinamide 3, followed by oxidation with m-CPBA. Suzuki coupling of 9 with the desired arylboronic acids, gave the expected biphenylsulfonylamino derivatives in satisfactory yields. Liberation of the phosphonic group by hydrogenolysis led to the desired (R)-alpha-biphenylsulfonylamino 2-methylpropyl phosphonates 14a-i. Screening of the new compounds on MMP-1, -2, -3, -7, -8, -9, -13 and -14 showed IC50 in the range of nM in most cases. (c) 2006 Elsevier Ltd. All rights reserved.
• Structural Insight into the Stereoselective Inhibition of MMP-8 by Enantiomeric Sulfonamide Phosphonates
  作者：Giorgio Pochetti、Enrico Gavuzzo、Cristina Campestre、Mariangela Agamennone、Paolo Tortorella、Valerio Consalvi、Carlo Gallina、Oliver Hiller、Harald Tschesche、Paul A. Tucker、Fernando Mazza

  DOI：10.1021/jm050787+

  日期：2006.2.1

  Potent and selective inhibitors of matrix metalloproteinases (MMPs), a family of zinc proteases that can degrade all the components of the extracellular matrix, could be useful for treatment of diseases such as cancer and arthritis. The most potent MMP inhibitors are based on hydroxamate as zinc-binding group (ZBG). alpha-Arylsulfonylamino phosphonates incorporate a particularly favorable combination of phosphonate as ZBG and arylsulfonylamino backbone so that their affinity exceptionally attains the nanomolar strength frequently observed for hydroxamate analogues. The detailed mode of binding of [1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate has been clarified by the crystal structures of the complexes that the R- and S-enantiomers respectively form with MMP-8. The reasons for the preferential MMP-8 inhibition by the R-phosphonate are underlined and the differences in the mode of binding of analogous alpha-arylsulfonylamino hydroxamates and carboxylates are discussed.