((R)-2-tert-Butoxycarbonylamino-propionylamino)-(4-difluoromethyl-2-methoxy-phenylsulfanyl)-acetic acid tert-butyl ester | 500897-93-8

• 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-tert-Butoxycarbonylamino-propionylamino)-(4-difluoromethyl-2-methoxy-phenylsulfanyl)-acetic acid tert-butyl ester
• 英文别名: tert-butyl 2-[4-(difluoromethyl)-2-methoxyphenyl]sulfanyl-2-[[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]acetate
• CAS: 500897-93-8
• 化学式: C₂₂H₃₂F₂N₂O₆S
• 分子量: 490.569
• InChiKey: UGRGORQKRNFDAS-GKOGFXNCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ((R)-2-tert-Butoxycarbonylamino-propionylamino)-(4-difluoromethyl-2-methoxy-phenylsulfanyl)-acetic acid tert-butyl ester 在 溶剂黄146 、 三氟乙酸 作用下， 反应 6.0h， 以44%的产率得到(R)-((R)-2-Amino-propionylamino)-(4-difluoromethyl-2-methoxy-phenylsulfanyl)-acetic acid
  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：

  ((R)-2-tert-Butoxycarbonylamino-propionylamino)-(4-formyl-2-methoxy-phenylsulfanyl)-acetic acid tert-butyl ester 在 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以47%的产率得到((R)-2-tert-Butoxycarbonylamino-propionylamino)-(4-difluoromethyl-2-methoxy-phenylsulfanyl)-acetic acid tert-butyl ester
  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