tert-butyl (2R)-3-methyl-2-[[4-(2-phenyltetrazol-5-yl)phenyl]sulfonylamino]butanoate | 203639-92-3

• 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 (2R)-3-methyl-2-[[4-(2-phenyltetrazol-5-yl)phenyl]sulfonylamino]butanoate
• CAS: 203639-92-3
• 化学式: C₂₂H₂₇N₅O₄S
• 分子量: 457.553
• InChiKey: INVUHGRHVIARET-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (2R)-3-methyl-2-[[4-(2-phenyltetrazol-5-yl)phenyl]sulfonylamino]butanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-3-Methyl-2-[4-(2-phenyl-2H-tetrazol-5-yl)-benzenesulfonylamino]-butyric acid
  参考文献：
  名称：

  Highly Selective and Orally Active Inhibitors of Type IV Collagenase (MMP-9 and MMP-2):  N-Sulfonylamino Acid Derivatives

  摘要：

  Various N-sulfonylamino acid derivatives were synthesized and evaluated for their in vitro and in vivo activities to inhibit type IV collagenase (MMP-9 and MMP-2). When the amino acid residue and the sulfonamide moiety were modified, their inhibitory activities were greatly affected by the structure of the sulfonamide moiety. A series of aryl sulfonamide derivatives containing biaryl, tetrazole, amide, and triple bond were found to be potent and highly selective inhibitors of MMP-9 and MMP-2 In addition, these compounds were orally active in animal models of tumor growth and metastasis. These results revealed the potential of the N-sulfonylamino acid derivatives as a new type of candidate drug for the treatment of cancer.

  DOI：

  10.1021/jm9707582
• 作为产物：
  描述：

  5-(4-bromophenyl)-2-phenyl-2H-tetrazole 在 N-甲基吗啉 、 正丁基锂 、 磺酰氯 、 二氧化硫 作用下， 以 二氯甲烷 为溶剂， 生成 tert-butyl (2R)-3-methyl-2-[[4-(2-phenyltetrazol-5-yl)phenyl]sulfonylamino]butanoate
  参考文献：
  名称：

  Highly Selective and Orally Active Inhibitors of Type IV Collagenase (MMP-9 and MMP-2):  N-Sulfonylamino Acid Derivatives

  摘要：

  Various N-sulfonylamino acid derivatives were synthesized and evaluated for their in vitro and in vivo activities to inhibit type IV collagenase (MMP-9 and MMP-2). When the amino acid residue and the sulfonamide moiety were modified, their inhibitory activities were greatly affected by the structure of the sulfonamide moiety. A series of aryl sulfonamide derivatives containing biaryl, tetrazole, amide, and triple bond were found to be potent and highly selective inhibitors of MMP-9 and MMP-2 In addition, these compounds were orally active in animal models of tumor growth and metastasis. These results revealed the potential of the N-sulfonylamino acid derivatives as a new type of candidate drug for the treatment of cancer.

  DOI：

  10.1021/jm9707582

文献信息

• Homology Modeling of Gelatinase Catalytic Domains and Docking Simulations of Novel Sulfonamide Inhibitors
  作者：Ryuichi Kiyama、Yoshinori Tamura、Fumihiko Watanabe、Hiroshige Tsuzuki、Mitsuaki Ohtani、Mitsuaki Yodo

  DOI：10.1021/jm980514x

  日期：1999.5.1

  Three-dimensional models for the catalytic domain of gelatinases (MMP-9 and -2) have been constructed based on the X-ray crystal structure of MMP-3. Conformations of the loop segment which forms the bottom half of the S1' subsite but shows conformational diversity among the crystal structures of other MMPs have been explored by simulated annealing of each gelatinase model complexed with two highly potent "probe"

  基于MMP-3的X射线晶体结构，建立了明胶酶催化域（MMP-9和-2）的三维模型。通过模拟退火与两种强效“探针”抑制剂复合的每种明胶酶模型，探索了形成S1'亚位点下半部分，但显示其他MMP晶体结构之间构象多样性的环段构象。基于环与探针抑制剂的形状互补性，从产生的构象组中为每种明胶酶选择了代表性的催化结构域模型。选择用于MMP-9的单一模型来解释我们新型磺酰胺抑制剂的构效关系。复杂模型的分子动力学（MD）模拟显示了我们抑制剂的结合机理的重要特征：（i）与催化锌离子配位的配体羧酸根和与Glu219侧链的氢键，（ii）磺酰基之一氧与主链NHs（Leu181和Ala182）形成氢键，（iii）磺酰基取代基与S1'亚位广泛疏水接触。磺酰胺CNSC扭转专有采用的gauche构型在通过适当地将取代基导入S1'亚位点来实现第三结合特征方面发挥着重要作用。根据磺酰基取代基的笔直伸长，抑制活性的提高归因于取代