BnSO2-D-Phe(3,4-diCl)-Pro-OMe | 1027423-36-4

• 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: BnSO2-D-Phe(3,4-diCl)-Pro-OMe
• 英文别名: methyl (2S)-1-[(2R)-2-(benzylsulfonylamino)-3-(3,4-dichlorophenyl)propanoyl]pyrrolidine-2-carboxylate
• CAS: 1027423-36-4
• 化学式: C₂₂H₂₄Cl₂N₂O₅S
• 分子量: 499.415
• InChiKey: HLSUIJPFXAWJEJ-UXHICEINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  BnSO2-D-Phe(3,4-diCl)-Pro-OMe 在 lithium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 为溶剂， 反应 8.0h， 生成 (S)-1-[(R)-3-(3,4-Dichloro-phenyl)-2-phenylmethanesulfonylamino-propionyl]-pyrrolidine-2-carboxylic acid (5-amino-thiophen-3-ylmethyl)-amide
  参考文献：
  名称：

  Discovery of a Novel, Selective, and Orally Bioavailable Class of Thrombin Inhibitors Incorporating Aminopyridyl Moieties at the P1 Position

  摘要：

  A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (K-i 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral Fl was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at Fl was a key step in our search for a clinical candidate.

  DOI：

  10.1021/jm970493r
• 作为产物：
  描述：

  D-3,4-二氯苯丙氨酸 在 sodium hydroxide 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 BnSO2-D-Phe(3,4-diCl)-Pro-OMe
  参考文献：
  名称：

  Discovery of a Novel, Selective, and Orally Bioavailable Class of Thrombin Inhibitors Incorporating Aminopyridyl Moieties at the P1 Position

  摘要：

  A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (K-i 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral Fl was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at Fl was a key step in our search for a clinical candidate.

  DOI：

  10.1021/jm970493r

文献信息

• Discovery of a Novel, Selective, and Orally Bioavailable Class of Thrombin Inhibitors Incorporating Aminopyridyl Moieties at the P1 Position
  作者：Dong-Mei Feng、Stephen J. Gardell、S. Dale Lewis、Mark G. Bock、Zhongguo Chen、Roger M. Freidinger、Adel M. Naylor-Olsen、Harri G. Ramjit、Richard Woltmann、Elizabeth P. Baskin、Joseph J. Lynch、Robert Lucas、Jules A. Shafer、Kimberley B. Dancheck、I-Wu Chen、Shi-Shan Mao、Julie A. Krueger、Timothy R. Hare、Anne M. Mulichak、Joseph P. Vacca

  DOI：10.1021/jm970493r

  日期：1997.11.1

  A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (K-i 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral Fl was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at Fl was a key step in our search for a clinical candidate.