(R)-2-(4'-Chloro-biphenyl-4-ylmethyl)-1,1-dioxo-1λ⁶-[1,2]thiazinane-3-carboxylic acid tert-butyl ester | 717912-86-2

• 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: (R)-2-(4'-Chloro-biphenyl-4-ylmethyl)-1,1-dioxo-1λ⁶-[1,2]thiazinane-3-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (3R)-2-[[4-(4-chlorophenyl)phenyl]methyl]-1,1-dioxothiazinane-3-carboxylate
• CAS: 717912-86-2
• 化学式: C₂₂H₂₆ClNO₄S
• 分子量: 435.972
• InChiKey: YIDIPUOGODAUOI-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-2-(4'-Chloro-biphenyl-4-ylmethyl)-1,1-dioxo-1λ⁶-[1,2]thiazinane-3-carboxylic acid tert-butyl ester 在 N-甲基吗啉 、 三氟乙酸 、 氯甲酸丙酯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 (3R)-N-hydroxy-2-((4'-chloro[1,1'-biphenyl]-4-yl)methyl)tetrahydro-2H-1,2-thiazine-3-carboxamide 1,1-dioxide
  参考文献：
  名称：

  Sultam Hydroxamates as Novel Matrix Metalloproteinase Inhibitors

  摘要：

  In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (NIMP-2 IC50 = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of 26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active site.

  DOI：

  10.1021/jm049833g
• 作为产物：
  描述：

  (R)-2-(4-Hydroxy-benzyl)-1,1-dioxo-1λ⁶-[1,2]thiazinane-3-carboxylic acid tert-butyl ester 在 palladium diacetate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 (R)-2-(4'-Chloro-biphenyl-4-ylmethyl)-1,1-dioxo-1λ⁶-[1,2]thiazinane-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Sultam Hydroxamates as Novel Matrix Metalloproteinase Inhibitors

  摘要：

  In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (NIMP-2 IC50 = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of 26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active site.

  DOI：

  10.1021/jm049833g

文献信息

• Sultam Hydroxamates as Novel Matrix Metalloproteinase Inhibitors
  作者：Robert J. Cherney、Ruowei Mo、Dayton T. Meyer、Karl D. Hardman、Rui-Qin Liu、Maryanne B. Covington、Mingxin Qian、Zelda R. Wasserman、David D. Christ、James M. Trzaskos、Robert C. Newton、Carl P. Decicco

  DOI：10.1021/jm049833g

  日期：2004.6.1

  In this communication we describe the design, synthesis, and evaluation of novel sultam hydroxamates 4 as MMP-2, -9, and -13 inhibitors. Compound 26 was found to be an active inhibitor (NIMP-2 IC50 = 1 nM) with 1000-fold selectivity over MMP-1 and good oral bioavailability (F = 43%) in mouse. An X-ray crystal structure of 26 in MMP-13 confirms the key hydrogen bonds and prime side binding in the active site.