N-((2,3-dihydrobenzofuran-5-yl)sulfonyl)-N-isopentyl-D-valine | 1356410-19-9

• 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: N-((2,3-dihydrobenzofuran-5-yl)sulfonyl)-N-isopentyl-D-valine
• CAS: 1356410-19-9
• 化学式: C₁₈H₂₇NO₅S
• 分子量: 369.482
• InChiKey: XVSMCPQMUWNAMV-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.77
• 重原子数：
  25.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  83.91
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-((2,3-dihydrobenzofuran-5-yl)sulfonyl)-N-isopentyl-D-valine 在 N-甲基吗啉 、 三乙基硅烷 、 2-Chloro-1,3-dimethylimidazolidinium hexafluorophosphate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (2R)-2-[2,3-dihydro-1-benzofuran-5-ylsulfonyl(3-methylbutyl)amino]-N-hydroxy-3-methylbutanamide
  参考文献：
  名称：

  Potent and selective 2-naphthylsulfonamide substituted hydroxamic acid inhibitors of matrix metalloproteinase-13

  摘要：

  The matrix metalloproteinase enzyme MMP-13 plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). An effective MMP-13 inhibitor would provide a disease modifying therapy for the treatment of arthritis, although this goal still continues to elude the pharmaceutical industry due to issues with safety. Our efforts have resulted in the discovery of a series of hydroxamic acid inhibitors of MMP-13 that do not significantly inhibit MMP-2 (gelatinase-1). MMP-2 has been implicated in the musculoskeletal side effects resulting from pan-MMP inhibition due to findings from spontaneously occurring human MMP-2 deletions. Analysis of the SAR of hundreds of previously prepared hydroxamate based MMP inhibitors lead us to 2-naphthylsulfonamide substituted hydroxamates which exhibited modest selectivity for MMP-13 versus MMP-2. This Letter describes the lead optimization of 1 and identification of inhibitors exhibiting >100-fold selectivity for MMP-13 over MMP-2 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.087
• 作为产物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-((2,3-dihydrobenzofuran-5-yl)sulfonyl)-N-isopentyl-D-valine
  参考文献：
  名称：

  Potent and selective 2-naphthylsulfonamide substituted hydroxamic acid inhibitors of matrix metalloproteinase-13

  摘要：

  The matrix metalloproteinase enzyme MMP-13 plays a key role in the degradation of type II collagen in cartilage and bone in osteoarthritis (OA). An effective MMP-13 inhibitor would provide a disease modifying therapy for the treatment of arthritis, although this goal still continues to elude the pharmaceutical industry due to issues with safety. Our efforts have resulted in the discovery of a series of hydroxamic acid inhibitors of MMP-13 that do not significantly inhibit MMP-2 (gelatinase-1). MMP-2 has been implicated in the musculoskeletal side effects resulting from pan-MMP inhibition due to findings from spontaneously occurring human MMP-2 deletions. Analysis of the SAR of hundreds of previously prepared hydroxamate based MMP inhibitors lead us to 2-naphthylsulfonamide substituted hydroxamates which exhibited modest selectivity for MMP-13 versus MMP-2. This Letter describes the lead optimization of 1 and identification of inhibitors exhibiting >100-fold selectivity for MMP-13 over MMP-2 (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.087