isocyanato-γ-methylleucine benzyl ester | 142381-33-7

• 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: isocyanato-γ-methylleucine benzyl ester
• 英文别名: Pentanoic acid, 2-isocyanato-4,4-dimethyl-, phenylmethyl ester, (S)-(9CI)；benzyl (2S)-2-isocyanato-4,4-dimethylpentanoate
• CAS: 142381-33-7
• 化学式: C₁₅H₁₉NO₃
• 分子量: 261.321
• InChiKey: PYDBNABCBVQGCY-ZDUSSCGKSA-N

物化性质

• 沸点：
  340.5±25.0 °C(Predicted)
• 密度：
  1.02±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  isocyanato-γ-methylleucine benzyl ester 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 N-(cis-2,6-dimethylpiperidinocarbonyl)-γ-methylleucyl-D-1-(methoxycarbonyl)tryptophan benzyl ester
  参考文献：
  名称：

  An Efficient Preparation of the Pseudopeptide Endothelin-B Receptor Selective Antagonist BQ-788

  摘要：

  The endothelins are a family of bicyclic 21 amino acid peptides that are potent and prolonged vasoconstrictors. BQ-788 is a modified tripeptide that is the only known highly potent and selective antagonist for the endothelin-B (ET(B)) receptor subtype discovered to date. Previous preparations of BQ-788 (N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucyl-D-1-(methoxycarbonyl)tryptophanyl-D-norleucine sodium salt) have suffered from several synthetic difficulties, including formation of the sterically hindered N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucine, racemization of tryptophan during carbamination, and the facile reduction of the indole ring of tryptophan during catalytic hydrogenation. In order to prepare sufficient quantities of BQ-788 for in vitro and in vivo evaluations of the physiological significance of the ET(B) receptor, we have developed an efficient solution phase multiple-gram synthetic strategy.

  DOI：

  10.1021/jo00130a028
• 作为产物：
  描述：

  N^α-(tert-butyloxycarbonyl)-γ-methylleucine benzyl ester 在 盐酸 、 甲烷 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 2.0h， 生成 isocyanato-γ-methylleucine benzyl ester
  参考文献：
  名称：

  An Efficient Preparation of the Pseudopeptide Endothelin-B Receptor Selective Antagonist BQ-788

  摘要：

  The endothelins are a family of bicyclic 21 amino acid peptides that are potent and prolonged vasoconstrictors. BQ-788 is a modified tripeptide that is the only known highly potent and selective antagonist for the endothelin-B (ET(B)) receptor subtype discovered to date. Previous preparations of BQ-788 (N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucyl-D-1-(methoxycarbonyl)tryptophanyl-D-norleucine sodium salt) have suffered from several synthetic difficulties, including formation of the sterically hindered N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucine, racemization of tryptophan during carbamination, and the facile reduction of the indole ring of tryptophan during catalytic hydrogenation. In order to prepare sufficient quantities of BQ-788 for in vitro and in vivo evaluations of the physiological significance of the ET(B) receptor, we have developed an efficient solution phase multiple-gram synthetic strategy.

  DOI：

  10.1021/jo00130a028

文献信息

• Peptides having endothelin antagonist activity, a process for preparation thereof and pharmaceutical compositions comprising the same
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0457195B1

  公开（公告）日：1998-04-15
• US5284828A
  申请人：——

  公开号：US5284828A

  公开（公告）日：1994-02-08
• US5430022A
  申请人：——

  公开号：US5430022A

  公开（公告）日：1995-07-04
• US5656604A
  申请人：——

  公开号：US5656604A

  公开（公告）日：1997-08-12
• An Efficient Preparation of the Pseudopeptide Endothelin-B Receptor Selective Antagonist BQ-788
  作者：John X. He、Wayne L. Cody、Annette M. Doherty

  DOI：10.1021/jo00130a028

  日期：1995.12

  The endothelins are a family of bicyclic 21 amino acid peptides that are potent and prolonged vasoconstrictors. BQ-788 is a modified tripeptide that is the only known highly potent and selective antagonist for the endothelin-B (ET(B)) receptor subtype discovered to date. Previous preparations of BQ-788 (N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucyl-D-1-(methoxycarbonyl)tryptophanyl-D-norleucine sodium salt) have suffered from several synthetic difficulties, including formation of the sterically hindered N-(cis-2,6-dimethylpiperidinocarbonyl)-gamma-methylleucine, racemization of tryptophan during carbamination, and the facile reduction of the indole ring of tryptophan during catalytic hydrogenation. In order to prepare sufficient quantities of BQ-788 for in vitro and in vivo evaluations of the physiological significance of the ET(B) receptor, we have developed an efficient solution phase multiple-gram synthetic strategy.