(2S)-N-[(1R)-5-azido-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]-1-[(2S)-2-(3-methylbutanoylamino)-3-trimethylsilylpropanoyl]pyrrolidine-2-carboxamide | 308088-57-5

• 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: (2S)-N-[(1R)-5-azido-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]-1-[(2S)-2-(3-methylbutanoylamino)-3-trimethylsilylpropanoyl]pyrrolidine-2-carboxamide
• CAS: 308088-57-5
• 化学式: C₃₁H₅₅BN₆O₅Si
• 分子量: 630.711
• InChiKey: BVTMENLIDBTSMX-PATBGVDCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.08
• 重原子数：
  44
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  111
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-N-[(1R)-5-azido-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]-1-[(2S)-2-(3-methylbutanoylamino)-3-trimethylsilylpropanoyl]pyrrolidine-2-carboxamide 在 三氯化硼 作用下， 以 二氯甲烷 为溶剂， 以65%的产率得到
  参考文献：
  名称：

  Selective boron-Containing thrombin inhibitors—X-ray analysis reveals surprising binding mode

  摘要：

  Based on the structural comparison of the S1 pocket in different trypsin-like serine proteases, a series of Boc-D-trimethylsilylalanine-proline-boro-X pinanediol derivatives, with boro-X being different amino boronic acids, have been synthesized as inhibitors of thrombin. Among the novel compounds, a number of derivatives were synthesized which appeared to have sidechain variants too big to fit into the S1 pocket. Nevertheless, these compounds inhibited thrombin in the nM range. The X-ray structure of one of these inhibitors bound to the active side of thrombin reveals that a new binding mode is responsible for these surprising results. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00147-4
• 作为产物：
  描述：

  (S)-2-tert-Butoxycarbonylamino-3-trimethylsilanyl-propionic acid 4-nitro-phenyl ester 在 盐酸 、 sodium azide 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 溶剂黄146 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 51.0h， 生成 (2S)-N-[(1R)-5-azido-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]-1-[(2S)-2-(3-methylbutanoylamino)-3-trimethylsilylpropanoyl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Selective boron-Containing thrombin inhibitors—X-ray analysis reveals surprising binding mode

  摘要：

  Based on the structural comparison of the S1 pocket in different trypsin-like serine proteases, a series of Boc-D-trimethylsilylalanine-proline-boro-X pinanediol derivatives, with boro-X being different amino boronic acids, have been synthesized as inhibitors of thrombin. Among the novel compounds, a number of derivatives were synthesized which appeared to have sidechain variants too big to fit into the S1 pocket. Nevertheless, these compounds inhibited thrombin in the nM range. The X-ray structure of one of these inhibitors bound to the active side of thrombin reveals that a new binding mode is responsible for these surprising results. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00147-4

文献信息

• Selective boron-Containing thrombin inhibitors—X-ray analysis reveals surprising binding mode
  作者：Anette von Matt、Claus Ehrhardt、Peter Burkhard、Rainer Metternich、Malcolm Walkinshaw、Carlo Tapparelli

  DOI：10.1016/s0968-0896(00)00147-4

  日期：2000.9

  Based on the structural comparison of the S1 pocket in different trypsin-like serine proteases, a series of Boc-D-trimethylsilylalanine-proline-boro-X pinanediol derivatives, with boro-X being different amino boronic acids, have been synthesized as inhibitors of thrombin. Among the novel compounds, a number of derivatives were synthesized which appeared to have sidechain variants too big to fit into the S1 pocket. Nevertheless, these compounds inhibited thrombin in the nM range. The X-ray structure of one of these inhibitors bound to the active side of thrombin reveals that a new binding mode is responsible for these surprising results. (C) 2000 Elsevier Science Ltd. All rights reserved.