((S)-2-{(S)-2-[(R)-5-Bromo-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.0^2,6]dec-4-yl)-pentylcarbamoyl]-pyrrolidin-1-yl}-2-oxo-1-trimethylsilanylmethyl-ethyl)-carbamic acid tert-butyl ester | 244782-28-3

• 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: ((S)-2-{(S)-2-[(R)-5-Bromo-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.0^2,6]dec-4-yl)-pentylcarbamoyl]-pyrrolidin-1-yl}-2-oxo-1-trimethylsilanylmethyl-ethyl)-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-[(2S)-2-[[(1R)-5-bromo-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-trimethylsilylpropan-2-yl]carbamate
• CAS: 244782-28-3
• 化学式: C₃₁H₅₅BBrN₃O₆Si
• 分子量: 684.595
• InChiKey: ABSWQOWGDLGFPL-BZPDUYDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.53
• 重原子数：
  43
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ((S)-2-{(S)-2-[(R)-5-Bromo-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.0^2,6]dec-4-yl)-pentylcarbamoyl]-pyrrolidin-1-yl}-2-oxo-1-trimethylsilanylmethyl-ethyl)-carbamic acid tert-butyl ester 在 palladium on activated charcoal sodium azide 、 氢气 作用下， 以 四氢呋喃 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 20.0 ℃ 、496.42 kPa 条件下， 反应 49.0h， 生成 tert-butyl N-[(2S)-1-[(2S)-2-[[(1R)-5-formamido-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]pentyl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-trimethylsilylpropan-2-yl]carbamate
  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 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 、 乙酸乙酯 为溶剂， 反应 41.5h， 生成 ((S)-2-{(S)-2-[(R)-5-Bromo-1-((1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-bora-tricyclo[6.1.1.0^2,6]dec-4-yl)-pentylcarbamoyl]-pyrrolidin-1-yl}-2-oxo-1-trimethylsilanylmethyl-ethyl)-carbamic acid tert-butyl ester
  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.