(R)-2-(4'-(4-chlorobenzyloxy)-N-isopropoxybiphenyl-4-ylsulfonamido)-3-methylbutanoic acid | 1178858-87-1

• 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: (R)-2-(4'-(4-chlorobenzyloxy)-N-isopropoxybiphenyl-4-ylsulfonamido)-3-methylbutanoic acid
• 英文别名: (2R)-2-[[4-[4-[(4-chlorophenyl)methoxy]phenyl]phenyl]sulfonyl-propan-2-yloxyamino]-3-methylbutanoic acid
• CAS: 1178858-87-1
• 化学式: C₂₇H₃₀ClNO₆S
• 分子量: 532.057
• InChiKey: WVQFDOPEJRATAP-AREMUKBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-2-(4'-(4-chlorobenzyloxy)-N-isopropoxybiphenyl-4-ylsulfonamido)-3-methylbutanoic acid 、 O-(叔丁基二甲基硅烷)羟胺 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以61%的产率得到(2R)-N-[tert-butyl(dimethyl)silyl]oxy-2-[[4-[4-[(4-chlorophenyl)methoxy]phenyl]phenyl]sulfonyl-propan-2-yloxyamino]-3-methylbutanamide
  参考文献：
  名称：

  N-O-Isopropyl Sulfonamido-Based Hydroxamates: Design, Synthesis and Biological Evaluation of Selective Matrix Metalloproteinase-13 Inhibitors as Potential Therapeutic Agents for Osteoarthritis

  摘要：

  Matrix metalloproteinase-13 (MMP-13) is a key enzyme implicated in the degradation of the extracellular matrix in osteoarthritis (OA). For this reason, MMP-13 synthetic inhibitors arc being sought as potential therapeutic agents to prevent cartilage degradation and to halt the progression of OA. Herein, we report the synthesis and in vitro evaluation of a new series of selective MMP-13 inhibitors possessing an arylsulfonamidic scaffold. Among these potential inhibitors, a very promising compound was discovered exhibiting nanomolar activity for MMP-13 and was highly selective for this enzyme compared to MMP-1, -14, and TACE. This compound acted as a slow-binding inhibitor of MMP-13 and was demonstrated to be effective in an in vitro Collagen assay and in a model of cartilage degradation. Furthermore, a docking study was conducted for this compound in order to investigate its binding interactions with MMP-13 and the reasons for its selectivity toward MMP-13 versus other MMPs.

  DOI：

  10.1021/jm900261f
• 作为产物：
  描述：

  tert-butyl (R)-2-(4'-(4-chlorobenzyloxy)-N-isopropoxybiphenyl-4-ylsulfonamido)-3-methylbutanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以78%的产率得到(R)-2-(4'-(4-chlorobenzyloxy)-N-isopropoxybiphenyl-4-ylsulfonamido)-3-methylbutanoic acid
  参考文献：
  名称：

  N-O-Isopropyl Sulfonamido-Based Hydroxamates: Design, Synthesis and Biological Evaluation of Selective Matrix Metalloproteinase-13 Inhibitors as Potential Therapeutic Agents for Osteoarthritis

  摘要：

  Matrix metalloproteinase-13 (MMP-13) is a key enzyme implicated in the degradation of the extracellular matrix in osteoarthritis (OA). For this reason, MMP-13 synthetic inhibitors arc being sought as potential therapeutic agents to prevent cartilage degradation and to halt the progression of OA. Herein, we report the synthesis and in vitro evaluation of a new series of selective MMP-13 inhibitors possessing an arylsulfonamidic scaffold. Among these potential inhibitors, a very promising compound was discovered exhibiting nanomolar activity for MMP-13 and was highly selective for this enzyme compared to MMP-1, -14, and TACE. This compound acted as a slow-binding inhibitor of MMP-13 and was demonstrated to be effective in an in vitro Collagen assay and in a model of cartilage degradation. Furthermore, a docking study was conducted for this compound in order to investigate its binding interactions with MMP-13 and the reasons for its selectivity toward MMP-13 versus other MMPs.

  DOI：

  10.1021/jm900261f