2-[isopentyl(4-methoxyphenyl)sulfonylamino]ethanehydroxamic acid

• 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: 2-[isopentyl(4-methoxyphenyl)sulfonylamino]ethanehydroxamic acid
• 英文别名: N-Hydroxy-2-[[4-methoxybenzenesulfonyl](3-methylbutyl)amino]acetamide；N-hydroxy-2-[(4-methoxybenzene)(3-methylbutyl)sulfonamido]acetamide；N-hydroxy-2-[(4-methoxyphenyl)sulfonyl-(3-methylbutyl)amino]acetamide
• 化学式: C₁₄H₂₂N₂O₅S
• 分子量: 330.405
• InChiKey: YPCPCLGFXANQDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  异戊胺 在 盐酸羟胺 、 sodium methylate 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 2.5h， 生成 2-[isopentyl(4-methoxyphenyl)sulfonylamino]ethanehydroxamic acid
  参考文献：
  名称：

  Discovery of CGS 27023A, a Non-Peptidic, Potent, and Orally Active Stromelysin Inhibitor That Blocks Cartilage Degradation in Rabbits

  摘要：

  Structure-activity relationships of a lead hydroxamic acid inhibitor of recombinant human stromelysin were systematically defined by taking advantage of a concise synthesis that allowed diverse functionality to be explored at each position in a template. An ex vivo rat model and an in vivo rabbit model of stromelysin-induced cartilage degradation were used to further optimize these analogs for oral activity and duration of action. The culmination of these modifications resulted in CGS 27023A, a potent, orally active stromelysin inhibitor that blocks the erosion of cartilage matrix.

  DOI：

  10.1021/jm960871c

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。
• Statin-MMP inhibitor combinations
  申请人：——

  公开号：US20020049237A1

  公开（公告）日：2002-04-25

  The invention is a pharmaceutical composition comprising an MMP inhibitor and a statin, said composition being useful for treating vascular diseases.

  这项发明是一种药物组合物，包括MMP抑制剂和他汀类药物，该组合物可用于治疗血管疾病。
• Use of matrix metalloproteinase inhibitors for treating neurological disorders and promoting wound healing
  申请人：WARNER-LAMBERT COMPANY LLC

  公开号：EP1366765A1

  公开（公告）日：2003-12-03

  Matrix metalloproteinase inhibitors are useful for preventing and treating neurological disorders and in promoting wound healing.

  基质金属蛋白酶抑制剂可用于预防和治疗神经系统疾病以及促进伤口愈合。
• Arylsulfonamido-substituted hydroxamic acids
  申请人：Novartis AG

  公开号：EP0606046B1

  公开（公告）日：1997-10-08
• ARYLSULFONAMIDO-SUBSTITUTED HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASE INHIBITORS
  申请人：Novartis AG

  公开号：EP0766672B1

  公开（公告）日：2000-10-04