Boc-D-Ala-DL-Ncy(Ph(2-For))-OtBu | 500897-92-7

• 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: Boc-D-Ala-DL-Ncy(Ph(2-For))-OtBu
• 英文别名: tert-butyl 2-(2-formylphenyl)sulfanyl-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]acetate
• CAS: 500897-92-7
• 化学式: C₂₁H₃₀N₂O₆S
• 分子量: 438.545
• InChiKey: LIHLDIXAVYGCLL-FWJOYPJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  136
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Boc-D-Ala-DL-Ncy(Ph(2-For))-OtBu 在 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 以51%的产率得到tert-butyl 2-[2-(difluoromethyl)phenyl]sulfanyl-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]acetate
  参考文献：
  名称：

  Design and Evaluation of Mechanism-Based Inhibitors of D-Alanyl-D-alanine Dipeptidase VanX

  摘要：

  VanX protein is 6 D-alanyl-D-alanine dipeptidase essential for vancomycin resistance in Enterococcus. It is also a key drug target in circumventing clinical glycopeptide antibiotic resistance. The dipeptide-like compound D-Ala-D-Gly(SC6H4-p-CHF2) (1) was recently reported as the first mechanism-based inhibitor with high affinity for the enzyme but poor inhibitory efficiency (k(inact)/K-irr = 9320 m(-1) s(-1)) and a high partition ratio (7600). In order to assess the effects of variations in aromatic substituents on the in vitro inhibition properties of 1, we have prepared a few derivatives and analyzed them using the alternative substrate D-Ala-D-Gly(SPh)-OH (15) designed according to a similar strategy. Whereas moving the electrophilic difluoromethyl group to the ortho position slightly improved the inhibition parameters (k(intact)/K-irr, = 1140 m(-1) s(-1)) with a small decrease in the partition ratio (7200), introduction of a methoxy group in D-Ala-D-ortho/para-(difluoromethyl)phenylthioglycines resulted in a marked decrease in inhibitory efficiency. These results demonstrate the difficulties in improving the leading compound 1 given the restricted space available at the VanX active site.

  DOI：

  10.1002/1099-0690(200211)2002:21<3573::aid-ejoc3573>3.0.co;2-v
• 作为产物：
  描述：

  2-硫代水杨醛 、 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 18.0h， 以78%的产率得到Boc-D-Ala-DL-Ncy(Ph(2-For))-OtBu
  参考文献：
  名称：

  Design and Evaluation of Mechanism-Based Inhibitors of D-Alanyl-D-alanine Dipeptidase VanX

  摘要：

  VanX protein is 6 D-alanyl-D-alanine dipeptidase essential for vancomycin resistance in Enterococcus. It is also a key drug target in circumventing clinical glycopeptide antibiotic resistance. The dipeptide-like compound D-Ala-D-Gly(SC6H4-p-CHF2) (1) was recently reported as the first mechanism-based inhibitor with high affinity for the enzyme but poor inhibitory efficiency (k(inact)/K-irr = 9320 m(-1) s(-1)) and a high partition ratio (7600). In order to assess the effects of variations in aromatic substituents on the in vitro inhibition properties of 1, we have prepared a few derivatives and analyzed them using the alternative substrate D-Ala-D-Gly(SPh)-OH (15) designed according to a similar strategy. Whereas moving the electrophilic difluoromethyl group to the ortho position slightly improved the inhibition parameters (k(intact)/K-irr, = 1140 m(-1) s(-1)) with a small decrease in the partition ratio (7200), introduction of a methoxy group in D-Ala-D-ortho/para-(difluoromethyl)phenylthioglycines resulted in a marked decrease in inhibitory efficiency. These results demonstrate the difficulties in improving the leading compound 1 given the restricted space available at the VanX active site.

  DOI：

  10.1002/1099-0690(200211)2002:21<3573::aid-ejoc3573>3.0.co;2-v

文献信息

• Design and Evaluation of Mechanism-Based Inhibitors of D-Alanyl-D-alanine Dipeptidase VanX
  作者：Loïc Yaouancq、Maria Anissimova、Marie-Ange Badet-Denisot、Bernard Badet

  DOI：10.1002/1099-0690(200211)2002:21<3573::aid-ejoc3573>3.0.co;2-v

  日期：2002.11

  VanX protein is 6 D-alanyl-D-alanine dipeptidase essential for vancomycin resistance in Enterococcus. It is also a key drug target in circumventing clinical glycopeptide antibiotic resistance. The dipeptide-like compound D-Ala-D-Gly(SC6H4-p-CHF2) (1) was recently reported as the first mechanism-based inhibitor with high affinity for the enzyme but poor inhibitory efficiency (k(inact)/K-irr = 9320 m(-1) s(-1)) and a high partition ratio (7600). In order to assess the effects of variations in aromatic substituents on the in vitro inhibition properties of 1, we have prepared a few derivatives and analyzed them using the alternative substrate D-Ala-D-Gly(SPh)-OH (15) designed according to a similar strategy. Whereas moving the electrophilic difluoromethyl group to the ortho position slightly improved the inhibition parameters (k(intact)/K-irr, = 1140 m(-1) s(-1)) with a small decrease in the partition ratio (7200), introduction of a methoxy group in D-Ala-D-ortho/para-(difluoromethyl)phenylthioglycines resulted in a marked decrease in inhibitory efficiency. These results demonstrate the difficulties in improving the leading compound 1 given the restricted space available at the VanX active site.