4-benzyloxy-2-nitrobenzenesulfonyl chloride | 238405-67-9

• 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: 4-benzyloxy-2-nitrobenzenesulfonyl chloride
• 英文别名: 4-(Benzyloxy)-2-nitrobenzene-1-sulfonyl chloride；2-nitro-4-phenylmethoxybenzenesulfonyl chloride
• CAS: 238405-67-9
• 化学式: C₁₃H₁₀ClNO₅S
• 分子量: 327.745
• InChiKey: IFCZAXFFMBGYAJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  97.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-benzyloxy-2-nitrobenzenesulfonyl chloride 在 palladium on activated charcoal N-甲基吗啉 、 potassium tert-butylate 、 氢气 、 铁粉 、 溶剂黄146 、 N,N-二异丙基乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 80.0 ℃ 、344.74 kPa 条件下， 反应 25.33h， 生成 methyl 2(R)-[7-(3,5-dimethylbenzyloxy)-2,3,4,5-tetrahydrobenzo[1,2,5-f]thiadiazepine-1,1-dioxide]propanoate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Benzothiadiazepine Hydroxamates as Selective Tumor Necrosis Factor-α Converting Enzyme Inhibitors

  摘要：

  Elevated levels of tumor necrosis factor-alpha (TNF-alpha) have been associated with several inflammatory diseases, and therefore, strategies for its suppression have become important targets in drug discovery. Our efforts to suppress TNF-alpha have centered on the inhibition of TNF-alpha converting enzyme (TACE) through the use of hydroxamate inhibitors. Starting from broad-spectrum matrix metalloproteinase (MMP) inhibitors, we have designed and synthesized novel benzothiadiazepines as potent and selective TACE inhibitors. The benzothiadiazepines were synthesized with variation in P1 and P1' in order to effect potency and selectivity. The inhibitors were evaluated versus porcine TACE (pTACE), and the initial selectivity was assessed with counterscreens of MMP-1, -2, and -9. Several potent and selective inhibitors were discovered with compound 41 being the most active against pTACE (K-i = 5 nM) while still maintaining good selectivity versus the MMP's (at least 75-fold). Most compounds were assessed in the human peripheral blood mononuclear cell assay (PBMC) and the human whole blood assay (WBA) to determine their ability to suppress TNF-alpha. Compound 32 was the most potent compound in the PBMC assay (IC50 = 0.35 muM), while compound 62 was the most active in the WBA (IC50 = 1.4 muM).

  DOI：

  10.1021/jm020475w
• 作为产物：
  描述：

  3-硝基-4-氨基苯酚 在 盐酸 、 potassium tert-butylate 、 三氟乙酸 、 sodium nitrite 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.66h， 生成 4-benzyloxy-2-nitrobenzenesulfonyl chloride
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Benzothiadiazepine Hydroxamates as Selective Tumor Necrosis Factor-α Converting Enzyme Inhibitors

  摘要：

  Elevated levels of tumor necrosis factor-alpha (TNF-alpha) have been associated with several inflammatory diseases, and therefore, strategies for its suppression have become important targets in drug discovery. Our efforts to suppress TNF-alpha have centered on the inhibition of TNF-alpha converting enzyme (TACE) through the use of hydroxamate inhibitors. Starting from broad-spectrum matrix metalloproteinase (MMP) inhibitors, we have designed and synthesized novel benzothiadiazepines as potent and selective TACE inhibitors. The benzothiadiazepines were synthesized with variation in P1 and P1' in order to effect potency and selectivity. The inhibitors were evaluated versus porcine TACE (pTACE), and the initial selectivity was assessed with counterscreens of MMP-1, -2, and -9. Several potent and selective inhibitors were discovered with compound 41 being the most active against pTACE (K-i = 5 nM) while still maintaining good selectivity versus the MMP's (at least 75-fold). Most compounds were assessed in the human peripheral blood mononuclear cell assay (PBMC) and the human whole blood assay (WBA) to determine their ability to suppress TNF-alpha. Compound 32 was the most potent compound in the PBMC assay (IC50 = 0.35 muM), while compound 62 was the most active in the WBA (IC50 = 1.4 muM).

  DOI：

  10.1021/jm020475w

文献信息

• Cyclic sulfonamide derivatives as metalloproteinase inhibitors
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：US06455522B1

  公开（公告）日：2002-09-24

  The present application describes novel lactams and derivatives thereof of formula I: or pharmaceutically acceptable salt forms thereof, wherein rings ring B is a 4-8 membered cyclic sulfonamide containing from 0-3 additional heteroatoms selected from N, O, and S, which are useful as metalloprotease inhibitors.

  本申请描述了新型内酰胺及其衍生物，其化学式为I：或其药学上可接受的盐形式，其中环B为4-8成员环状磺酰胺，含有0-3个额外的杂原子，所选的杂原子为N、O和S，这些化合物可用作金属蛋白酶抑制剂。
• BORON-CONTAINING SMALL MOLECULES
  申请人：Hernandez Vincent S.

  公开号：US20110212918A1

  公开（公告）日：2011-09-01

  This invention relates to, among other items, 6-substituted benzoxaborole compounds and their use for treating bacterial infections.

  本发明涉及6-取代苯并氧硼烷化合物等物品，以及它们用于治疗细菌感染的用途。
• NOVEL CYCLIC SULFONAMIDE DERIVATIVES AS METALLOPROTEINASE INHIBITORS
  申请人：Du Pont Pharmaceuticals Company

  公开号：EP1054877A1

  公开（公告）日：2000-11-29
• US6455522B1
  申请人：——

  公开号：US6455522B1

  公开（公告）日：2002-09-24
• [EN] NOVEL CYCLIC SULFONAMIDE DERIVATIVES AS METALLOPROTEINASE INHIBITORS<br/>[FR] NOUVEAUX SULFAMIDES CYCLIQUES UTILISES COMME INHIBITEURS DES METALLOPROTEASES
  申请人：DU PONT PHARMACEUTICALS COMPANY

  公开号：WO1999041246A1

  公开（公告）日：1999-08-19

  (EN) The present application describes novel lactams and derivatives thereof of formula (I) or pharmaceutically acceptable salt forms thereof, wherein ring B is a 4-8 membered cyclic sulfonamide containing from 0-3 additional heteroatoms selected from N, O, and S, which are useful as metalloprotease inhibitors.(FR) L'invention concerne de nouveaux lactames, leurs dérivés et leurs sels pharmaceutiquement acceptables, de formule (I), dans laquelle le noyau B est un sulfamide cyclique constitué de 4 à 8 éléments renfermant 0 à 3 hétéroatomes supplémentaires choisis entre N, O et S. Ces composés sont utiles comme inhibiteurs des métalloprotéases.